Daily Papers

Understanding biological processes, drug development, and biotechnological advancements requires detailed analysis of protein structures and sequences, a task in protein research that is inherently complex and time-consuming when performed manually. To streamline this process, we introduce ProteinGPT, a state-of-the-art multi-modal protein chat system, that allows users to upload protein sequences and/or structures for comprehensive protein analysis and responsive inquiries. ProteinGPT seamlessly integrates protein sequence and structure encoders with linear projection layers for precise representation adaptation, coupled with a large language model (LLM) to generate accurate and contextually relevant responses. To train ProteinGPT, we construct a large-scale dataset of 132,092 proteins with annotations, and optimize the instruction-tuning process using GPT-4o. This innovative system ensures accurate alignment between the user-uploaded data and prompts, simplifying protein analysis. Experiments show that ProteinGPT can produce promising responses to proteins and their corresponding questions.

Building a working mental model of a protein typically requires weeks of reading, cross-referencing crystal and predicted structures, and inspecting ligand complexes, an effort that is slow, unevenly accessible, and often requires specialized computational skills. We introduce Speak to a Protein, a new capability that turns protein analysis into an interactive, multimodal dialogue with an expert co-scientist. The AI system retrieves and synthesizes relevant literature, structures, and ligand data; grounds answers in a live 3D scene; and can highlight, annotate, manipulate and see the visualization. It also generates and runs code when needed, explaining results in both text and graphics. We demonstrate these capabilities on relevant proteins, posing questions about binding pockets, conformational changes, or structure-activity relationships to test ideas in real-time. Speak to a Protein reduces the time from question to evidence, lowers the barrier to advanced structural analysis, and enables hypothesis generation by tightly coupling language, code, and 3D structures. Speak to a Protein is freely accessible at https://open.playmolecule.org.

Motivation: Proteins are of great significance in living organisms. However, understanding their functions encounters numerous challenges, such as insufficient integration of multimodal information, a large number of training parameters, limited flexibility of classification-based methods, and the lack of systematic evaluation metrics for protein Q&A systems. To tackle these issues, we propose the Prot2Chat framework. Results: We modified ProteinMPNN to encode protein sequence and structural information in a unified way. We used a large language model (LLM) to encode questions into vectors and developed a protein-text adapter to compress protein information into virtual tokens based on these vectors, achieving the early fusion of text and protein information. Finally, the same LLM reads the virtual tokens and the questions to generate answers. To optimize training efficiency, we froze the encoder and employed Low-Rank Adaptation (LoRA) techniques for the LLM. Experiments on two datasets show that both automated metrics and expert evaluations demonstrate the superior performance of our model, and zero-shot prediction results highlight its generalization ability. The models and codes are available at https://github.com/ wangzc1233/Prot2Chat. Contact: zqcao@suda.edu.cn or wangzc025@163.com Key words: Protein Q&A, Early-Fusion, LLM

As Large Language Models (LLMs) rapidly evolve, their influence in science is becoming increasingly prominent. The emerging capabilities of LLMs in task generalization and free-form dialogue can significantly advance fields like chemistry and biology. However, the field of single-cell biology, which forms the foundational building blocks of living organisms, still faces several challenges. High knowledge barriers and limited scalability in current methods restrict the full exploitation of LLMs in mastering single-cell data, impeding direct accessibility and rapid iteration. To this end, we introduce ChatCell, which signifies a paradigm shift by facilitating single-cell analysis with natural language. Leveraging vocabulary adaptation and unified sequence generation, ChatCell has acquired profound expertise in single-cell biology and the capability to accommodate a diverse range of analysis tasks. Extensive experiments further demonstrate ChatCell's robust performance and potential to deepen single-cell insights, paving the way for more accessible and intuitive exploration in this pivotal field. Our project homepage is available at https://zjunlp.github.io/project/ChatCell.

Recent advancements in conversational large language models (LLMs), such as ChatGPT, have demonstrated remarkable promise in various domains, including drug discovery. However, existing works mainly focus on investigating the capabilities of conversational LLMs on chemical reaction and retrosynthesis. While drug editing, a critical task in the drug discovery pipeline, remains largely unexplored. To bridge this gap, we propose ChatDrug, a framework to facilitate the systematic investigation of drug editing using LLMs. ChatDrug jointly leverages a prompt module, a retrieval and domain feedback (ReDF) module, and a conversation module to streamline effective drug editing. We empirically show that ChatDrug reaches the best performance on 33 out of 39 drug editing tasks, encompassing small molecules, peptides, and proteins. We further demonstrate, through 10 case studies, that ChatDrug can successfully identify the key substructures (e.g., the molecule functional groups, peptide motifs, and protein structures) for manipulation, generating diverse and valid suggestions for drug editing. Promisingly, we also show that ChatDrug can offer insightful explanations from a domain-specific perspective, enhancing interpretability and enabling informed decision-making. This research sheds light on the potential of ChatGPT and conversational LLMs for drug editing. It paves the way for a more efficient and collaborative drug discovery pipeline, contributing to the advancement of pharmaceutical research and development.

Recent advancements in specialized large-scale architectures for training image and language have profoundly impacted the field of computer vision and natural language processing (NLP). Language models, such as the recent ChatGPT and GPT4 have demonstrated exceptional capabilities in processing, translating, and generating human languages. These breakthroughs have also been reflected in protein research, leading to the rapid development of numerous new methods in a short time, with unprecedented performance. Language models, in particular, have seen widespread use in protein research, as they have been utilized to embed proteins, generate novel ones, and predict tertiary structures. In this book chapter, we provide an overview of the use of protein generative models, reviewing 1) language models for the design of novel artificial proteins, 2) works that use non-Transformer architectures, and 3) applications in directed evolution approaches.

Large language models have already demonstrated their formidable capabilities in general domains, ushering in a revolutionary transformation. However, exploring and exploiting the extensive knowledge of these models to comprehend multi-omics biology remains underexplored. To fill this research gap, we first introduce Biology-Instructions, the first large-scale multi-omics biological sequences-related instruction-tuning dataset including DNA, RNA, proteins, and multi-molecules, designed to bridge the gap between large language models (LLMs) and complex biological sequences-related tasks. This dataset can enhance the versatility of LLMs by integrating diverse biological sequenced-based prediction tasks with advanced reasoning capabilities, while maintaining conversational fluency. Additionally, we reveal significant performance limitations in even state-of-the-art LLMs on biological sequence-related multi-omics tasks without specialized pre-training and instruction-tuning. We further develop a strong baseline called ChatMultiOmics with a novel three-stage training pipeline, demonstrating the powerful ability to understand biology by using Biology-Instructions. Biology-Instructions and ChatMultiOmics are publicly available and crucial resources for enabling more effective integration of LLMs with multi-omics sequence analysis.

In recent years, protein-text models have gained significant attention for their potential in protein generation and understanding. Current approaches focus on integrating protein-related knowledge into large language models through continued pretraining and multi-modal alignment, enabling simultaneous comprehension of textual descriptions and protein sequences. Through a thorough analysis of existing model architectures and text-based protein understanding benchmarks, we identify significant data leakage issues present in current benchmarks. Moreover, conventional metrics derived from natural language processing fail to accurately assess the model's performance in this domain. To address these limitations, we reorganize existing datasets and introduce a novel evaluation framework based on biological entities. Motivated by our observation, we propose a retrieval-enhanced method, which significantly outperforms fine-tuned LLMs for protein-to-text generation and shows accuracy and efficiency in training-free scenarios. Our code and data can be seen at https://github.com/IDEA-XL/RAPM.

Collecting and annotating task-oriented dialog data is difficult, especially for highly specific domains that require expert knowledge. At the same time, informal communication channels such as instant messengers are increasingly being used at work. This has led to a lot of work-relevant information that is disseminated through those channels and needs to be post-processed manually by the employees. To alleviate this problem, we present TexPrax, a messaging system to collect and annotate problems, causes, and solutions that occur in work-related chats. TexPrax uses a chatbot to directly engage the employees to provide lightweight annotations on their conversation and ease their documentation work. To comply with data privacy and security regulations, we use an end-to-end message encryption and give our users full control over their data which has various advantages over conventional annotation tools. We evaluate TexPrax in a user-study with German factory employees who ask their colleagues for solutions on problems that arise during their daily work. Overall, we collect 202 task-oriented German dialogues containing 1,027 sentences with sentence-level expert annotations. Our data analysis also reveals that real-world conversations frequently contain instances with code-switching, varying abbreviations for the same entity, and dialects which NLP systems should be able to handle.

This paper presents the development of a specialized chatbot for materials science, leveraging the Llama-2 language model, and continuing pre-training on the expansive research articles in the materials science domain from the S2ORC dataset. The methodology involves an initial pretraining phase on over one million domain-specific papers, followed by an instruction-tuning process to refine the chatbot's capabilities. The chatbot is designed to assist researchers, educators, and students by providing instant, context-aware responses to queries in the field of materials science. We make the four trained checkpoints (7B, 13B, with or without chat ability) freely available to the research community at https://github.com/Xianjun-Yang/Quokka.

This paper presents UMASS_BioNLP team participation in the MEDIQA-Chat 2023 shared task for Task-A and Task-C. We focus especially on Task-C and propose a novel LLMs cooperation system named a doctor-patient loop to generate high-quality conversation data sets. The experiment results demonstrate that our approaches yield reasonable performance as evaluated by automatic metrics such as ROUGE, medical concept recall, BLEU, and Self-BLEU. Furthermore, we conducted a comparative analysis between our proposed method and ChatGPT and GPT-4. This analysis also investigates the potential of utilizing cooperation LLMs to generate high-quality datasets.

System messages play a crucial role in interactions with large language models (LLMs), often serving as prompts to initiate conversations. Through system messages, users can assign specific roles, perform intended tasks, incorporate background information, specify various output formats and communication styles. Despite such versatility, publicly available data are often lack system messages and subject to strict license constraints in the industry field. Manual labeling of publicly available data with system messages that align with user instructions demands significant resources. In view of such challenges, our work introduces SysGen, a pipeline for generating system messages with better aligned assistant responses from the supervised fine-tuning dataset without system messages. Training on SysGen data has demonstrated substantial improvements in the alignment of model responses with system messages and user instructions, as demonstrated across various open-source models on the Multifacet benchmark, while maintaining minimal impact on other unseen benchmarks such as Open LLM Leaderboard 2. Our qualitative analysis highlights the importance of diverse system messages to ensure better adaptability across different contexts.

Protein-protein interactions (PPIs) are fundamental to numerous cellular processes, and their characterization is vital for understanding disease mechanisms and guiding drug discovery. While protein language models (PLMs) have demonstrated remarkable success in predicting protein structure and function, their application to sequence-based PPI binding affinity prediction remains relatively underexplored. This gap is often attributed to the scarcity of high-quality, rigorously refined datasets and the reliance on simple strategies for concatenating protein representations. In this work, we address these limitations. First, we introduce a meticulously curated version of the PPB-Affinity dataset of a total of 8,207 unique protein-protein interaction entries, by resolving annotation inconsistencies and duplicate entries for multi-chain protein interactions. This dataset incorporates a stringent, less than or equal to 30%, sequence identity threshold to ensure robust splitting into training, validation, and test sets, minimizing data leakage. Second, we propose and systematically evaluate four architectures for adapting PLMs to PPI binding affinity prediction: embeddings concatenation (EC), sequences concatenation (SC), hierarchical pooling (HP), and pooled attention addition (PAD). These architectures were assessed using two training methods: full fine-tuning and a lightweight approach employing ConvBERT heads over frozen PLM features. Our comprehensive experiments across multiple leading PLMs (ProtT5, ESM2, Ankh, Ankh2, and ESM3) demonstrated that the HP and PAD architectures consistently outperform conventional concatenation methods, achieving up to 12% increase in terms of Spearman correlation. These results highlight the necessity of sophisticated architectural designs to fully exploit the capabilities of PLMs for nuanced PPI binding affinity prediction.

Protein language models (PLMs) have emerged as powerful tools to detect complex patterns of protein sequences. However, the capability of PLMs to fully capture information on protein sequences might be limited by focusing on single pre-training tasks. Although adding data modalities or supervised objectives can improve the performance of PLMs, pre-training often remains focused on denoising corrupted sequences. To push the boundaries of PLMs, our research investigated a multi-task pre-training strategy. We developed Ankh3, a model jointly optimized on two objectives: masked language modeling with multiple masking probabilities and protein sequence completion relying only on protein sequences as input. This multi-task pre-training demonstrated that PLMs can learn richer and more generalizable representations solely from protein sequences. The results demonstrated improved performance in downstream tasks, such as secondary structure prediction, fluorescence, GB1 fitness, and contact prediction. The integration of multiple tasks gave the model a more comprehensive understanding of protein properties, leading to more robust and accurate predictions.

A ChatGPT-like system for drug compounds could be a game-changer in pharmaceutical research, accelerating drug discovery, enhancing our understanding of structure-activity relationships, guiding lead optimization, aiding drug repurposing, reducing the failure rate, and streamlining clinical trials. In this work, we make an initial attempt towards enabling ChatGPT-like capabilities on drug molecule graphs, by developing a prototype system DrugChat. DrugChat works in a similar way as ChatGPT. Users upload a compound molecule graph and ask various questions about this compound. DrugChat will answer these questions in a multi-turn, interactive manner. The DrugChat system consists of a graph neural network (GNN), a large language model (LLM), and an adaptor. The GNN takes a compound molecule graph as input and learns a representation for this graph. The adaptor transforms the graph representation produced by the GNN into another representation that is acceptable to the LLM. The LLM takes the compound representation transformed by the adaptor and users' questions about this compound as inputs and generates answers. All these components are trained end-to-end. To train DrugChat, we collected instruction tuning datasets which contain 10,834 drug compounds and 143,517 question-answer pairs. The code and data is available at https://github.com/UCSD-AI4H/drugchat

The complex nature of big biological systems pushed some scientists to classify its understanding under the inconceivable missions. Different leveled challenges complicated this task, one of is the prediction of a protein's function. In recent years, significant progress has been made in this field through the development of various machine learning approaches. However, most existing methods formulate the task as a multi-classification problem, i.e assigning predefined labels to proteins. In this work, we propose a novel approach, Prot2Text, which predicts a protein function's in a free text style, moving beyond the conventional binary or categorical classifications. By combining Graph Neural Networks(GNNs) and Large Language Models(LLMs), in an encoder-decoder framework, our model effectively integrates diverse data types including proteins' sequences, structures, and textual annotations. This multimodal approach allows for a holistic representation of proteins' functions, enabling the generation of detailed and accurate descriptions. To evaluate our model, we extracted a multimodal protein dataset from SwissProt, and demonstrate empirically the effectiveness of Prot2Text. These results highlight the transformative impact of multimodal models, specifically the fusion of GNNs and LLMs, empowering researchers with powerful tools for more accurate prediction of proteins' functions. The code, the models and a demo will be publicly released.

Proteins are essential to life's processes, underpinning evolution and diversity. Advances in sequencing technology have revealed millions of proteins, underscoring the need for sophisticated pre-trained protein models for biological analysis and AI development. Facebook's ESM2, the most advanced protein language model to date, leverages a masked prediction task for unsupervised learning, crafting amino acid representations with notable biochemical accuracy. Yet, it lacks in delivering functional protein insights, signaling an opportunity for enhancing representation quality.Our study addresses this gap by incorporating protein family classification into ESM2's training.This approach, augmented with Community Propagation-Based Clustering Algorithm, improves global protein representations, while a contextual prediction task fine-tunes local amino acid accuracy. Significantly, our model achieved state-of-the-art results in several downstream experiments, demonstrating the power of combining global and local methodologies to substantially boost protein representation quality.

Protein language models are a powerful tool for learning protein representations through pre-training on vast protein sequence datasets. However, traditional protein language models lack explicit structural supervision, despite its relevance to protein function. To address this issue, we introduce the integration of remote homology detection to distill structural information into protein language models without requiring explicit protein structures as input. We evaluate the impact of this structure-informed training on downstream protein function prediction tasks. Experimental results reveal consistent improvements in function annotation accuracy for EC number and GO term prediction. Performance on mutant datasets, however, varies based on the relationship between targeted properties and protein structures. This underscores the importance of considering this relationship when applying structure-aware training to protein function prediction tasks. Code and model weights are available at https://github.com/DeepGraphLearning/esm-s.

Self-supervised training of language models (LMs) has seen great success for protein sequences in learning meaningful representations and for generative drug design. Most protein LMs are based on the Transformer architecture trained on individual proteins with short context lengths. Such protein LMs cannot extrapolate to longer proteins and protein complexes well. They also fail to account for the underlying biological mechanisms carried out by biomolecular interactions and dynamics i.e., proteins often interact with other proteins, molecules, and pathways in complex biological systems. In this work, we propose LC-PLM based on an alternative protein LM architecture, BiMamba-S, built off selective structured state-space models, to learn high-quality universal protein representations at the amino acid token level using masked language modeling. We also introduce its graph-contextual variant, LC-PLM-G, which contextualizes protein-protein interaction (PPI) graphs for a second stage of training. LC-PLM demonstrates favorable neural scaling laws, better length extrapolation capability, and a 7% to 34% improvement on protein downstream tasks than Transformer-based ESM-2. LC-PLM-G further trained within the context of PPI graphs shows promising results on protein structure and function prediction tasks. Our study demonstrates the benefit of increasing the context size with computationally efficient LM architecture (e.g. structured state space models) in learning universal protein representations and incorporating molecular interaction context contained in biological graphs.

Recent advances in Language Models have enabled the protein modeling community with a powerful tool since protein sequences can be represented as text. Specifically, by taking advantage of Transformers, sequence-to-property prediction will be amenable without the need for explicit structural data. In this work, inspired by recent progress in Large Language Models (LLMs), we introduce PeptideBERT, a protein language model for predicting three key properties of peptides (hemolysis, solubility, and non-fouling). The PeptideBert utilizes the ProtBERT pretrained transformer model with 12 attention heads and 12 hidden layers. We then finetuned the pretrained model for the three downstream tasks. Our model has achieved state of the art (SOTA) for predicting Hemolysis, which is a task for determining peptide's potential to induce red blood cell lysis. Our PeptideBert non-fouling model also achieved remarkable accuracy in predicting peptide's capacity to resist non-specific interactions. This model, trained predominantly on shorter sequences, benefits from the dataset where negative examples are largely associated with insoluble peptides. Codes, models, and data used in this study are freely available at: https://github.com/ChakradharG/PeptideBERT

Complex cell signaling systems -- governed by varying protein abundances and interactions -- generate diverse cell types across organs. These systems evolve under influences such as age, sex, diet, environmental exposures, and diseases, making them challenging to decode given the involvement of tens of thousands of genes and proteins. Recently, hundreds of millions of single-cell omics data have provided a robust foundation for understanding these signaling networks within various cell subpopulations and conditions. Inspired by the success of large foundation models (for example, large language models and large vision models) pre-trained on massive datasets, we introduce OmniCellTOSG, the first dataset of cell text-omic signaling graphs (TOSGs). Each TOSG represents the signaling network of an individual or meta-cell and is labeled with information such as organ, disease, sex, age, and cell subtype. OmniCellTOSG offers two key contributions. First, it introduces a novel graph model that integrates human-readable annotations -- such as biological functions, cellular locations, signaling pathways, related diseases, and drugs -- with quantitative gene and protein abundance data, enabling graph reasoning to decode cell signaling. This approach calls for new joint models combining large language models and graph neural networks. Second, the dataset is built from single-cell RNA sequencing data of approximately 120 million cells from diverse tissues and conditions (healthy and diseased) and is fully compatible with PyTorch. This facilitates the development of innovative cell signaling models that could transform research in life sciences, healthcare, and precision medicine. The OmniCellTOSG dataset is continuously expanding and will be updated regularly. The dataset and code are available at https://github.com/FuhaiLiAiLab/OmniCellTOSG.

As large language models (LLMs) increasingly permeate daily lives, there is a growing demand for real-time interactions that mirror human conversations. Traditional turn-based chat systems driven by LLMs prevent users from verbally interacting with the system while it is generating responses. To overcome these limitations, we adapt existing LLMs to duplex models so that these LLMs can listen for users while generating output and dynamically adjust themselves to provide users with instant feedback. % such as in response to interruptions. Specifically, we divide the queries and responses of conversations into several time slices and then adopt a time-division-multiplexing (TDM) encoding-decoding strategy to pseudo-simultaneously process these slices. Furthermore, to make LLMs proficient enough to handle real-time conversations, we build a fine-tuning dataset consisting of alternating time slices of queries and responses as well as covering typical feedback types in instantaneous interactions. Our experiments show that although the queries and responses of conversations are segmented into incomplete slices for processing, LLMs can preserve their original performance on standard benchmarks with a few fine-tuning steps on our dataset. Automatic and human evaluation indicate that duplex models make user-AI interactions more natural and human-like, and greatly improve user satisfaction compared to vanilla LLMs. Our duplex model and dataset will be released.

Large language models have shown good performances in generating code to meet human requirements. However, human requirements expressed in natural languages can be vague, incomplete, and ambiguous, leading large language models to misunderstand human requirements and make mistakes. Worse, it is difficult for a human user to refine the requirement. To help human users refine their requirements and improve large language models' code generation performances, we propose ChatCoder: a method to refine the requirements via chatting with large language models. We design a chat scheme in which the large language models will guide the human users to refine their expression of requirements to be more precise, unambiguous, and complete than before. Experiments show that ChatCoder has improved existing large language models' performance by a large margin. Besides, ChatCoder has the advantage over refine-based methods and LLMs fine-tuned via human response.

Large language models (LLMs) have performed well in providing general and extensive health suggestions in single-turn conversations, exemplified by systems such as ChatGPT, ChatGLM, ChatDoctor, DoctorGLM, and etc. However, the limited information provided by users during single turn results in inadequate personalization and targeting of the generated suggestions, which requires users to independently select the useful part. It is mainly caused by the missing ability to engage in multi-turn questioning. In real-world medical consultations, doctors usually employ a series of iterative inquiries to comprehend the patient's condition thoroughly, enabling them to provide effective and personalized suggestions subsequently, which can be defined as chain of questioning (CoQ) for LLMs. To improve the CoQ of LLMs, we propose BianQue, a ChatGLM-based LLM finetuned with the self-constructed health conversation dataset BianQueCorpus that is consist of multiple turns of questioning and health suggestions polished by ChatGPT. Experimental results demonstrate that the proposed BianQue can simultaneously balance the capabilities of both questioning and health suggestions, which will help promote the research and application of LLMs in the field of proactive health.

Recent large language models (LLMs) in the general domain, such as ChatGPT, have shown remarkable success in following instructions and producing human-like responses. However, such language models have not been learned individually and carefully for the medical domain, resulting in poor diagnostic accuracy and inability to give correct recommendations for medical diagnosis, medications, etc. To address this issue, we collected more than 700 diseases and their corresponding symptoms, recommended medications, and required medical tests, and then generated 5K doctor-patient conversations. By fine-tuning models of doctor-patient conversations, these models emerge with great potential to understand patients' needs, provide informed advice, and offer valuable assistance in a variety of medical-related fields. The integration of these advanced language models into healthcare can revolutionize the way healthcare professionals and patients communicate, ultimately improving the overall quality of care and patient outcomes. In addition, we will open all source code, datasets and model weights to advance the further development of dialogue models in the medical field. In addition, the training data, code, and weights of this project are available at: https://github.com/Kent0n-Li/ChatDoctor.

Current AI-assisted protein design mainly utilizes protein sequential and structural information. Meanwhile, there exists tremendous knowledge curated by humans in the text format describing proteins' high-level properties. Yet, whether the incorporation of such text data can help protein design tasks has not been explored. To bridge this gap, we propose ProteinDT, a multi-modal framework that leverages textual descriptions for protein design. ProteinDT consists of three subsequent steps: ProteinCLAP that aligns the representation of two modalities, a facilitator that generates the protein representation from the text modality, and a decoder that generates the protein sequences from the representation. To train ProteinDT, we construct a large dataset, SwissProtCLAP, with 441K text and protein pairs. We empirically verify the effectiveness of ProteinDT from three aspects: (1) consistently superior performance on four out of six protein property prediction benchmarks; (2) over 90% accuracy for text-guided protein generation; and (3) promising results for zero-shot text-guided protein editing.

Protein language models have shown remarkable success in learning biological information from protein sequences. However, most existing models are limited by either autoencoding or autoregressive pre-training objectives, which makes them struggle to handle protein understanding and generation tasks concurrently. We propose a unified protein language model, xTrimoPGLM, to address these two types of tasks simultaneously through an innovative pre-training framework. Our key technical contribution is an exploration of the compatibility and the potential for joint optimization of the two types of objectives, which has led to a strategy for training xTrimoPGLM at an unprecedented scale of 100 billion parameters and 1 trillion training tokens. Our extensive experiments reveal that 1) xTrimoPGLM significantly outperforms other advanced baselines in 18 protein understanding benchmarks across four categories. The model also facilitates an atomic-resolution view of protein structures, leading to an advanced 3D structural prediction model that surpasses existing language model-based tools. 2) xTrimoPGLM not only can generate de novo protein sequences following the principles of natural ones, but also can perform programmable generation after supervised fine-tuning (SFT) on curated sequences. These results highlight the substantial capability and versatility of xTrimoPGLM in understanding and generating protein sequences, contributing to the evolving landscape of foundation models in protein science.

The advent of large language models (LLMs) has made it possible to generate natural written dialogues between two agents. However, generating human-like spoken dialogues from these written dialogues remains challenging. Spoken dialogues have several unique characteristics: they frequently include backchannels and laughter, and the smoothness of turn-taking significantly influences the fluidity of conversation. This study proposes CHATS - CHatty Agents Text-to-Speech - a discrete token-based system designed to generate spoken dialogues based on written dialogues. Our system can generate speech for both the speaker side and the listener side simultaneously, using only the transcription from the speaker side, which eliminates the need for transcriptions of backchannels or laughter. Moreover, CHATS facilitates natural turn-taking; it determines the appropriate duration of silence after each utterance in the absence of overlap, and it initiates the generation of overlapping speech based on the phoneme sequence of the next utterance in case of overlap. Experimental evaluations indicate that CHATS outperforms the text-to-speech baseline, producing spoken dialogues that are more interactive and fluid while retaining clarity and intelligibility.

This research presents a comprehensive methodology for utilizing an ontology-driven structured prompts system in interplay with ChatGPT, a widely used large language model (LLM). The study develops formal models, both information and functional, and establishes the methodological foundations for integrating ontology-driven prompts with ChatGPT's meta-learning capabilities. The resulting productive triad comprises the methodological foundations, advanced information technology, and the OntoChatGPT system, which collectively enhance the effectiveness and performance of chatbot systems. The implementation of this technology is demonstrated using the Ukrainian language within the domain of rehabilitation. By applying the proposed methodology, the OntoChatGPT system effectively extracts entities from contexts, classifies them, and generates relevant responses. The study highlights the versatility of the methodology, emphasizing its applicability not only to ChatGPT but also to other chatbot systems based on LLMs, such as Google's Bard utilizing the PaLM 2 LLM. The underlying principles of meta-learning, structured prompts, and ontology-driven information retrieval form the core of the proposed methodology, enabling their adaptation and utilization in various LLM-based systems. This versatile approach opens up new possibilities for NLP and dialogue systems, empowering developers to enhance the performance and functionality of chatbot systems across different domains and languages.

The integration of biomolecular modeling with natural language (BL) has emerged as a promising interdisciplinary area at the intersection of artificial intelligence, chemistry and biology. This approach leverages the rich, multifaceted descriptions of biomolecules contained within textual data sources to enhance our fundamental understanding and enable downstream computational tasks such as biomolecule property prediction. The fusion of the nuanced narratives expressed through natural language with the structural and functional specifics of biomolecules described via various molecular modeling techniques opens new avenues for comprehensively representing and analyzing biomolecules. By incorporating the contextual language data that surrounds biomolecules into their modeling, BL aims to capture a holistic view encompassing both the symbolic qualities conveyed through language as well as quantitative structural characteristics. In this review, we provide an extensive analysis of recent advancements achieved through cross modeling of biomolecules and natural language. (1) We begin by outlining the technical representations of biomolecules employed, including sequences, 2D graphs, and 3D structures. (2) We then examine in depth the rationale and key objectives underlying effective multi-modal integration of language and molecular data sources. (3) We subsequently survey the practical applications enabled to date in this developing research area. (4) We also compile and summarize the available resources and datasets to facilitate future work. (5) Looking ahead, we identify several promising research directions worthy of further exploration and investment to continue advancing the field. The related resources and contents are updating in https://github.com/QizhiPei/Awesome-Biomolecule-Language-Cross-Modeling.

Therapeutic peptides have emerged as a pivotal modality in modern drug discovery, occupying a chemically and topologically rich space. While accurate prediction of their physicochemical properties is essential for accelerating peptide development, existing molecular language models rely on representations that fail to capture this complexity. Atom-level SMILES notation generates long token sequences and obscures cyclic topology, whereas amino-acid-level representations cannot encode the diverse chemical modifications central to modern peptide design. To bridge this representational gap, the Hierarchical Editing Language for Macromolecules (HELM) offers a unified framework enabling precise description of both monomer composition and connectivity, making it a promising foundation for peptide language modeling. Here, we propose HELM-BERT, the first encoder-based peptide language model trained on HELM notation. Based on DeBERTa, HELM-BERT is specifically designed to capture hierarchical dependencies within HELM sequences. The model is pre-trained on a curated corpus of 39,079 chemically diverse peptides spanning linear and cyclic structures. HELM-BERT significantly outperforms state-of-the-art SMILES-based language models in downstream tasks, including cyclic peptide membrane permeability prediction and peptide-protein interaction prediction. These results demonstrate that HELM's explicit monomer- and topology-aware representations offer substantial data-efficiency advantages for modeling therapeutic peptides, bridging a long-standing gap between small-molecule and protein language models.

We aim to produce a smaller language model that is aligned to user intent. Previous research has shown that applying distilled supervised fine-tuning (dSFT) on larger models significantly improves task accuracy; however, these models are unaligned, i.e. they do not respond well to natural prompts. To distill this property, we experiment with the use of preference data from AI Feedback (AIF). Starting from a dataset of outputs ranked by a teacher model, we apply distilled direct preference optimization (dDPO) to learn a chat model with significantly improved intent alignment. The approach requires only a few hours of training without any additional sampling during fine-tuning. The final result, Zephyr-7B, sets the state-of-the-art on chat benchmarks for 7B parameter models, and requires no human annotation. In particular, results on MT-Bench show that Zephyr-7B surpasses Llama2-Chat-70B, the best open-access RLHF-based model. Code, models, data, and tutorials for the system are available at https://github.com/huggingface/alignment-handbook.

Protein language models (pLMs) pre-trained on vast protein sequence databases excel at various downstream tasks but lack the structural knowledge essential for many biological applications. To address this, we integrate structural insights from pre-trained protein graph neural networks (pGNNs) into pLMs through a latent-level contrastive learning task. This task aligns residue representations from pLMs with those from pGNNs across multiple proteins, enriching pLMs with inter-protein structural knowledge. Additionally, we incorporate a physical-level task that infuses intra-protein structural knowledge by optimizing pLMs to predict structural tokens. The proposed dual-task framework effectively incorporates both inter-protein and intra-protein structural knowledge into pLMs. Given the variability in the quality of protein structures in PDB, we further introduce a residue loss selection module, which uses a small model trained on high-quality structures to select reliable yet challenging residue losses for the pLM to learn. Applying our structure alignment method to the state-of-the-art ESM2 and AMPLIFY results in notable performance gains across a wide range of tasks, including a 12.7% increase in ESM2 contact prediction. The data, code, and resulting SaESM2 and SaAMPLIFY models will be released on Hugging Face.

We consider incorporating topic information into the sequence-to-sequence framework to generate informative and interesting responses for chatbots. To this end, we propose a topic aware sequence-to-sequence (TA-Seq2Seq) model. The model utilizes topics to simulate prior knowledge of human that guides them to form informative and interesting responses in conversation, and leverages the topic information in generation by a joint attention mechanism and a biased generation probability. The joint attention mechanism summarizes the hidden vectors of an input message as context vectors by message attention, synthesizes topic vectors by topic attention from the topic words of the message obtained from a pre-trained LDA model, and let these vectors jointly affect the generation of words in decoding. To increase the possibility of topic words appearing in responses, the model modifies the generation probability of topic words by adding an extra probability item to bias the overall distribution. Empirical study on both automatic evaluation metrics and human annotations shows that TA-Seq2Seq can generate more informative and interesting responses, and significantly outperform the-state-of-the-art response generation models.

Dialogue-based language models mark a huge milestone in the field of artificial intelligence, by their impressive ability to interact with users, as well as a series of challenging tasks prompted by customized instructions. However, the prevalent large-scale dialogue-based language models like ChatGPT still have room for improvement, such as unstable responses to questions and the inability to think cooperatively like humans. Considering the ability of dialogue-based language models in conversation and their inherent randomness in thinking, we propose ChatLLM network that allows multiple dialogue-based language models to interact, provide feedback, and think together. We design the network of ChatLLMs based on ChatGPT. Specifically, individual instances of ChatGPT may possess distinct perspectives towards the same problem, and by consolidating these diverse viewpoints via a separate ChatGPT, the ChatLLM network system can conduct decision-making more objectively and comprehensively. In addition, a language-based feedback mechanism comparable to backpropagation is devised to update the ChatGPTs within the network. Experiments on two datasets demonstrate that our network attains significant improvements in problem-solving, leading to observable progress amongst each member.

This paper proposes a chatbot framework that adopts a hybrid model which consists of a knowledge graph and a text similarity model. Based on this chatbot framework, we build HHH, an online question-and-answer (QA) Healthcare Helper system for answering complex medical questions. HHH maintains a knowledge graph constructed from medical data collected from the Internet. HHH also implements a novel text representation and similarity deep learning model, Hierarchical BiLSTM Attention Model (HBAM), to find the most similar question from a large QA dataset. We compare HBAM with other state-of-the-art language models such as bidirectional encoder representation from transformers (BERT) and Manhattan LSTM Model (MaLSTM). We train and test the models with a subset of the Quora duplicate questions dataset in the medical area. The experimental results show that our model is able to achieve a superior performance than these existing methods.

The emergence of pretrained large language models has led to the deployment of a range of social chatbots for chitchat. Although these chatbots demonstrate language ability and fluency, they are not guaranteed to be engaging and can struggle to retain users. This work investigates the development of social chatbots that prioritize user engagement to enhance retention, specifically examining the use of human feedback to efficiently develop highly engaging chatbots. The proposed approach uses automatic pseudo-labels collected from user interactions to train a reward model that can be used to reject low-scoring sample responses generated by the chatbot model at inference time. Intuitive evaluation metrics, such as mean conversation length (MCL), are introduced as proxies to measure the level of engagement of deployed chatbots. A/B testing on groups of 10,000 new daily chatbot users on the Chai Research platform shows that this approach increases the MCL by up to 70%, which translates to a more than 30% increase in user retention for a GPT-J 6B model. Future work aims to use the reward model to realise a data fly-wheel, where the latest user conversations can be used to alternately fine-tune the language model and the reward model.

The rise of big data has amplified the need for efficient, user-friendly automated machine learning (AutoML) tools. However, the intricacy of understanding domain-specific data and defining prediction tasks necessitates human intervention making the process time-consuming while preventing full automation. Instead, envision an intelligent agent capable of assisting users in conducting AutoML tasks through intuitive, natural conversations without requiring in-depth knowledge of the underlying machine learning (ML) processes. This agent's key challenge is to accurately comprehend the user's prediction goals and, consequently, formulate precise ML tasks, adjust data sets and model parameters accordingly, and articulate results effectively. In this paper, we take a pioneering step towards this ambitious goal by introducing a ChatGPT-based conversational data-science framework to act as a "personal data scientist". Precisely, we utilize Large Language Models (ChatGPT) to build a natural interface between the users and the ML models (Scikit-Learn), which in turn, allows us to approach this ambitious problem with a realistic solution. Our model pivots around four dialogue states: Data Visualization, Task Formulation, Prediction Engineering, and Result Summary and Recommendation. Each state marks a unique conversation phase, impacting the overall user-system interaction. Multiple LLM instances, serving as "micro-agents", ensure a cohesive conversation flow, granting us granular control over the conversation's progression. In summary, we developed an end-to-end system that not only proves the viability of the novel concept of conversational data science but also underscores the potency of LLMs in solving complex tasks. Interestingly, its development spotlighted several critical weaknesses in the current LLMs (ChatGPT) and highlighted substantial opportunities for improvement.

Protein language models (PLMs) encode rich biological information, yet their internal neuron representations are poorly understood. We introduce the first automated framework for labeling every neuron in a PLM with biologically grounded natural language descriptions. Unlike prior approaches relying on sparse autoencoders or manual annotation, our method scales to hundreds of thousands of neurons, revealing individual neurons are selectively sensitive to diverse biochemical and structural properties. We then develop a novel neuron activation-guided steering method to generate proteins with desired traits, enabling convergence to target biochemical properties like molecular weight and instability index as well as secondary and tertiary structural motifs, including alpha helices and canonical Zinc Fingers. We finally show that analysis of labeled neurons in different model sizes reveals PLM scaling laws and a structured neuron space distribution.

The development of Open-Domain Dialogue Systems (ODS)is a trending topic due to the large number of research challenges, large societal and business impact, and advances in the underlying technology. However, the development of these kinds of systems requires two important characteristics:1) automatic evaluation mechanisms that show high correlations with human judgements across multiple dialogue evaluation aspects (with explainable features for providing constructive and explicit feedback on the quality of generative models' responses for quick development and deployment)and 2) mechanisms that can help to control chatbot responses,while avoiding toxicity and employing intelligent ways to handle toxic user comments and keeping interaction flow and engagement. This track at the 10th Dialogue System Technology Challenge (DSTC10) is part of the ongoing effort to promote scalable and toxic-free ODS. This paper describes the datasets and baselines provided to participants, as well as submission evaluation results for each of the two proposed subtasks.

Predicting which proteins interact together from amino-acid sequences is an important task. We develop a method to pair interacting protein sequences which leverages the power of protein language models trained on multiple sequence alignments, such as MSA Transformer and the EvoFormer module of AlphaFold. We formulate the problem of pairing interacting partners among the paralogs of two protein families in a differentiable way. We introduce a method called DiffPALM that solves it by exploiting the ability of MSA Transformer to fill in masked amino acids in multiple sequence alignments using the surrounding context. MSA Transformer encodes coevolution between functionally or structurally coupled amino acids. We show that it captures inter-chain coevolution, while it was trained on single-chain data, which means that it can be used out-of-distribution. Relying on MSA Transformer without fine-tuning, DiffPALM outperforms existing coevolution-based pairing methods on difficult benchmarks of shallow multiple sequence alignments extracted from ubiquitous prokaryotic protein datasets. It also outperforms an alternative method based on a state-of-the-art protein language model trained on single sequences. Paired alignments of interacting protein sequences are a crucial ingredient of supervised deep learning methods to predict the three-dimensional structure of protein complexes. DiffPALM substantially improves the structure prediction of some eukaryotic protein complexes by AlphaFold-Multimer, without significantly deteriorating any of those we tested. It also achieves competitive performance with using orthology-based pairing.

Interacting with a software system via a chatbot can be challenging, especially when the chatbot needs to generate API calls, in the right order and with the right parameters, to communicate with the system. API calling in chatbot systems poses significant challenges, particularly in complex, multi-step tasks requiring accurate API selection and execution. We contribute to this domain in three ways: first, by introducing a novel dataset designed to assess models on API function selection, parameter generation, and nested API calls; second, by benchmarking state-of-the-art language models across varying levels of complexity to evaluate their performance in API function generation and parameter accuracy; and third, by proposing an enhanced API routing method that combines general-purpose large language models for API selection with fine-tuned models for parameter generation and some prompt engineering approach. These approaches lead to substantial improvements in handling complex API tasks, offering practical advancements for real-world API-driven chatbot systems.

To support software developers in finding and fixing software bugs, several automated program repair techniques have been introduced. Given a test suite, standard methods usually either synthesize a repair, or navigate a search space of software edits to find test-suite passing variants. Recent program repair methods are based on deep learning approaches. One of these novel methods, which is not primarily intended for automated program repair, but is still suitable for it, is ChatGPT. The bug fixing performance of ChatGPT, however, is so far unclear. Therefore, in this paper we evaluate ChatGPT on the standard bug fixing benchmark set, QuixBugs, and compare the performance with the results of several other approaches reported in the literature. We find that ChatGPT's bug fixing performance is competitive to the common deep learning approaches CoCoNut and Codex and notably better than the results reported for the standard program repair approaches. In contrast to previous approaches, ChatGPT offers a dialogue system through which further information, e.g., the expected output for a certain input or an observed error message, can be entered. By providing such hints to ChatGPT, its success rate can be further increased, fixing 31 out of 40 bugs, outperforming state-of-the-art.

Traditional applications of natural language processing (NLP) in healthcare have predominantly focused on patient-centered services, enhancing patient interactions and care delivery, such as through medical dialogue systems. However, the potential of NLP to benefit inexperienced doctors, particularly in areas such as communicative medical coaching, remains largely unexplored. We introduce ``ChatCoach,'' an integrated human-AI cooperative framework. Within this framework, both a patient agent and a coaching agent collaboratively support medical learners in practicing their medical communication skills during consultations. Unlike traditional dialogue systems, ChatCoach provides a simulated environment where a human doctor can engage in medical dialogue with a patient agent. Simultaneously, a coaching agent provides real-time feedback to the doctor. To construct the ChatCoach system, we developed a dataset and integrated Large Language Models such as ChatGPT and Llama2, aiming to assess their effectiveness in communicative medical coaching tasks. Our comparative analysis demonstrates that instruction-tuned Llama2 significantly outperforms ChatGPT's prompting-based approaches.

Large Language Models (LLMs) have revolutionized the field of natural language processing, but they fall short in comprehending biological sequences such as proteins. To address this challenge, we propose InstructProtein, an innovative LLM that possesses bidirectional generation capabilities in both human and protein languages: (i) taking a protein sequence as input to predict its textual function description and (ii) using natural language to prompt protein sequence generation. To achieve this, we first pre-train an LLM on both protein and natural language corpora, enabling it to comprehend individual languages. Then supervised instruction tuning is employed to facilitate the alignment of these two distinct languages. Herein, we introduce a knowledge graph-based instruction generation framework to construct a high-quality instruction dataset, addressing annotation imbalance and instruction deficits in existing protein-text corpus. In particular, the instructions inherit the structural relations between proteins and function annotations in knowledge graphs, which empowers our model to engage in the causal modeling of protein functions, akin to the chain-of-thought processes in natural languages. Extensive experiments on bidirectional protein-text generation tasks show that InstructProtein outperforms state-of-the-art LLMs by large margins. Moreover, InstructProtein serves as a pioneering step towards text-based protein function prediction and sequence design, effectively bridging the gap between protein and human language understanding.

Large language models (LLMs) have shown incredible capabilities and transcended the natural language processing (NLP) community, with adoption throughout many services like healthcare, therapy, education, and customer service. Since users include people with critical information needs like students or patients engaging with chatbots, the safety of these systems is of prime importance. Therefore, a clear understanding of the capabilities and limitations of LLMs is necessary. To this end, we systematically evaluate toxicity in over half a million generations of ChatGPT, a popular dialogue-based LLM. We find that setting the system parameter of ChatGPT by assigning it a persona, say that of the boxer Muhammad Ali, significantly increases the toxicity of generations. Depending on the persona assigned to ChatGPT, its toxicity can increase up to 6x, with outputs engaging in incorrect stereotypes, harmful dialogue, and hurtful opinions. This may be potentially defamatory to the persona and harmful to an unsuspecting user. Furthermore, we find concerning patterns where specific entities (e.g., certain races) are targeted more than others (3x more) irrespective of the assigned persona, that reflect inherent discriminatory biases in the model. We hope that our findings inspire the broader AI community to rethink the efficacy of current safety guardrails and develop better techniques that lead to robust, safe, and trustworthy AI systems.

Large language models (LLMs) have made impressive progress in chemistry applications, including molecular property prediction, molecular generation, experimental protocol design, etc. However, the community lacks a dialogue-based model specifically designed for chemistry. The challenge arises from the fact that most chemical data and scientific knowledge are primarily stored in structured databases, and the direct use of these structured data compromises the model's ability to maintain coherent dialogue. To tackle this issue, we develop a novel template-based instruction construction method that transforms structured knowledge into plain dialogue, making it suitable for language model training. By leveraging this approach, we develop ChemLLM, the first large language model dedicated to chemistry, capable of performing various tasks across chemical disciplines with smooth dialogue interaction. ChemLLM beats GPT-3.5 on all three principal tasks in chemistry, i.e., name conversion, molecular caption, and reaction prediction, and surpasses GPT-4 on two of them. Remarkably, ChemLLM also shows exceptional adaptability to related mathematical and physical tasks despite being trained mainly on chemical-centric corpora. Furthermore, ChemLLM demonstrates proficiency in specialized NLP tasks within chemistry, such as literature translation and cheminformatic programming. ChemLLM opens up a new avenue for exploration within chemical studies, while our method of integrating structured chemical knowledge into dialogue systems sets a new frontier for developing LLMs across various scientific fields. Codes, Datasets, and Model weights are publicly accessible at hf.co/AI4Chem/ChemLLM-7B-Chat.

Understanding and designing biomolecules, such as proteins and small molecules, is central to advancing drug discovery, synthetic biology, and enzyme engineering. Recent breakthroughs in Artificial Intelligence (AI) have revolutionized biomolecular research, achieving remarkable accuracy in biomolecular prediction and design. However, a critical gap remains between AI's computational power and researchers' intuition, using natural language to align molecular complexity with human intentions. Large Language Models (LLMs) have shown potential to interpret human intentions, yet their application to biomolecular research remains nascent due to challenges including specialized knowledge requirements, multimodal data integration, and semantic alignment between natural language and biomolecules. To address these limitations, we present InstructBioMol, a novel LLM designed to bridge natural language and biomolecules through a comprehensive any-to-any alignment of natural language, molecules, and proteins. This model can integrate multimodal biomolecules as input, and enable researchers to articulate design goals in natural language, providing biomolecular outputs that meet precise biological needs. Experimental results demonstrate InstructBioMol can understand and design biomolecules following human instructions. Notably, it can generate drug molecules with a 10% improvement in binding affinity and design enzymes that achieve an ESP Score of 70.4, making it the only method to surpass the enzyme-substrate interaction threshold of 60.0 recommended by the ESP developer. This highlights its potential to transform real-world biomolecular research.

Software engineering is a domain characterized by intricate decision-making processes, often relying on nuanced intuition and consultation. Recent advancements in deep learning have started to revolutionize software engineering practices through elaborate designs implemented at various stages of software development. In this paper, we present an innovative paradigm that leverages large language models (LLMs) throughout the entire software development process, streamlining and unifying key processes through natural language communication, thereby eliminating the need for specialized models at each phase. At the core of this paradigm lies ChatDev, a virtual chat-powered software development company that mirrors the established waterfall model, meticulously dividing the development process into four distinct chronological stages: designing, coding, testing, and documenting. Each stage engages a team of agents, such as programmers, code reviewers, and test engineers, fostering collaborative dialogue and facilitating a seamless workflow. The chat chain acts as a facilitator, breaking down each stage into atomic subtasks. This enables dual roles, allowing for proposing and validating solutions through context-aware communication, leading to efficient resolution of specific subtasks. The instrumental analysis of ChatDev highlights its remarkable efficacy in software generation, enabling the completion of the entire software development process in under seven minutes at a cost of less than one dollar. It not only identifies and alleviates potential vulnerabilities but also rectifies potential hallucinations while maintaining commendable efficiency and cost-effectiveness. The potential of ChatDev unveils fresh possibilities for integrating LLMs into the realm of software development.

Foundation models (FMs) have exhibited remarkable performance across a wide range of downstream tasks in many domains. Nevertheless, general-purpose FMs often face challenges when confronted with domain-specific problems, due to their limited access to the proprietary training data in a particular domain. In biomedicine, there are various biological modalities, such as molecules, proteins, and cells, which are encoded by the language of life and exhibit significant modality gaps with human natural language. In this paper, we introduce BioMedGPT, an open multimodal generative pre-trained transformer (GPT) for biomedicine, to bridge the gap between the language of life and human natural language. BioMedGPT allows users to easily ``communicate'' with diverse biological modalities through free text, which is the first of its kind. BioMedGPT aligns different biological modalities with natural language via a large generative language model, namely, BioMedGPT-LM. We publish BioMedGPT-10B, which unifies the feature spaces of molecules, proteins, and natural language via encoding and alignment. Through fine-tuning, BioMedGPT-10B outperforms or is on par with human and significantly larger general-purpose foundation models on the biomedical QA task. It also demonstrates promising performance in the molecule QA and protein QA tasks, which could greatly accelerate the discovery of new drugs and therapeutic targets. In addition, BioMedGPT-LM-7B is the first large generative language model based on Llama2 in the biomedical domain, therefore is commercial friendly. Both BioMedGPT-10B and BioMedGPT-LM-7B are open-sourced to the research community. In addition, we publish the datasets that are meticulously curated for the alignment of multi-modalities, i.e., PubChemQA and UniProtQA. All the models, codes, and datasets are available at https://github.com/PharMolix/OpenBioMed.

Building a general-purpose task model similar to ChatGPT has been an important research direction for gene large language models. Instruction fine-tuning is a key component in building ChatGPT, but existing instructions are primarily based on natural language. Natural language and gene sequences have significant differences in tokenization and encoding. Therefore, constructing a multilingual model that can handle both natural language and gene sequences is crucial for solving this problem.In this paper, we expand the capabilities of the LLaMA large language model to include gene language. This involves expanding the vocabulary using the Byte Pair Encoding (BPE) method, specifically tailored for DNA and protein sequences, and conducting further pre-training on these sequences. We then convert various downstream gene task data into a unified format for instruction fine-tuning and further fine-tune the model on this data.Our study demonstrates that a mixed model of gene and natural language, fine-tuned with instructions, achieves results comparable to the current state-of-the-art (SOTA) in tasks such as gene classification and gene sequence interaction. This provides a promising direction for building a unified large language model for gene tasks.

With the advancements in conversational AI, such as ChatGPT, this paper focuses on exploring developing Large Language Models (LLMs) for non-English languages, especially emphasizing alignment with human preferences. We introduce a computationally efficient method, leveraging chat vector, to synergize pre-existing knowledge and behaviors in LLMs, restructuring the conventional training paradigm from continual pre-train -> SFT -> RLHF to continual pre-train + chat vector. Our empirical studies, primarily focused on Traditional Chinese, employ LLaMA2 as the base model and acquire the chat vector by subtracting the pre-trained weights, LLaMA2, from the weights of LLaMA2-chat. Evaluating from three distinct facets, which are toxicity, ability of instruction following, and multi-turn dialogue demonstrates the chat vector's superior efficacy in chatting. To confirm the adaptability of our approach, we extend our experiments to include models pre-trained in both Korean and Simplified Chinese, illustrating the versatility of our methodology. Overall, we present a significant solution in aligning LLMs with human preferences efficiently across various languages, accomplished by the chat vector.

Current Large Language Models (LLMs) for understanding proteins primarily treats amino acid sequences as a text modality. Meanwhile, Protein Language Models (PLMs), such as ESM-2, have learned massive sequential evolutionary knowledge from the universe of natural protein sequences. Furthermore, structure-based encoders like ProteinMPNN learn the structural information of proteins through Graph Neural Networks. However, whether the incorporation of protein encoders can enhance the protein understanding of LLMs has not been explored. To bridge this gap, we propose EvoLlama, a multimodal framework that connects a structure-based encoder, a sequence-based protein encoder and an LLM for protein understanding. EvoLlama consists of a ProteinMPNN structure encoder, an ESM-2 protein sequence encoder, a multimodal projector to align protein and text representations and a Llama-3 text decoder. To train EvoLlama, we fine-tune it on protein-oriented instructions and protein property prediction datasets verbalized via natural language instruction templates. Our experiments show that EvoLlama's protein understanding capabilities have been significantly enhanced, outperforming other fine-tuned protein-oriented LLMs in zero-shot settings by an average of 1%-8% and surpassing the state-of-the-art baseline with supervised fine-tuning by an average of 6%. On protein property prediction datasets, our approach achieves promising results that are competitive with state-of-the-art task-specific baselines. We will release our code in a future version.

Proteins are fundamental to biology, executing diverse functions through complex physicochemical interactions, and they hold transformative potential across medicine, materials science, and environmental applications. Protein Language Models (pLMs) aim to unlock insights from the vast space of unlabeled protein sequences by learning rich, semantic representations from primary sequences via masked language modeling. However, these models typically exhibit limited generative capacity. In this work, we introduce the Diffusion Sequence Model (DSM), a novel pLM trained with masked diffusion to enable both high-quality representation learning and generative protein design. DSM builds upon the ESM2 architecture by incorporating a masked forward diffusion process inspired by the LLaDA framework. After training, DSM is capable of generating diverse, biomimetic sequences that align with expected amino acid compositions, secondary structures, and predicted functions, even with 90\% token corruption. Furthermore, DSM's learned representations match or exceed those of similarly sized pLMs on downstream tasks. We also introduce DSM(ppi), a variant fine-tuned to generate protein binders by attending to target sequences. We demonstrate DSM(ppi)'s effectiveness on the challenging Bench-tested Binder Benchmark (BenchBB), where both DSM and DSM(ppi) produce candidates with superior predicted binding affinity compared to known binders. Our results establish masked diffusion as a powerful paradigm for unifying protein representation and generation in a single framework.

Large-scale language models (LLMs), such as ChatGPT, are becoming increasingly sophisticated and exhibit human-like capabilities, playing an essential role in assisting humans in a variety of everyday tasks. An important application of AI is interactive recommendation systems that respond to human inquiries and make recommendations tailored to the user. In most conventional interactive recommendation systems, the language model is used only as a dialogue model, and there is a separate recommendation system. This is due to the fact that the language model used as a dialogue system does not have the capability to serve as a recommendation system. Therefore, we will realize the construction of a dialogue system with recommendation capability by using OpenAI's Chat-GPT, which has a very high inference capability as a dialogue system and the ability to generate high-quality sentences, and verify the effectiveness of the system.

Instant messaging has become a predominant form of communication, with texts and emoticons enabling users to express emotions and ideas efficiently. Emoticons, in particular, have gained significant traction as a medium for conveying sentiments and information, leading to the growing importance of emoticon retrieval and recommendation systems. However, one of the key challenges in this area has been the absence of datasets that capture both the temporal dynamics and user-specific interactions with emoticons, limiting the progress of personalized user modeling and recommendation approaches. To address this, we introduce the emoticon dataset, a comprehensive resource that includes time-based data along with anonymous user identifiers across different conversations. As the largest publicly accessible emoticon dataset to date, it comprises 22K unique users, 370K emoticons, and 8.3M messages. The data was collected from a widely-used messaging platform across 67 conversations and 720 hours of crawling. Strict privacy and safety checks were applied to ensure the integrity of both text and image data. Spanning across 10 distinct domains, the emoticon dataset provides rich insights into temporal, multilingual, and cross-domain behaviors, which were previously unavailable in other emoticon-based datasets. Our in-depth experiments, both quantitative and qualitative, demonstrate the dataset's potential in modeling user behavior and personalized recommendation systems, opening up new possibilities for research in personalized retrieval and conversational AI. The dataset is freely accessible.

Large language models (LLMs) like ChatGPT and Gemini have significantly advanced natural language processing, enabling various applications such as chatbots and automated content generation. However, these models can be exploited by malicious individuals who craft toxic prompts to elicit harmful or unethical responses. These individuals often employ jailbreaking techniques to bypass safety mechanisms, highlighting the need for robust toxic prompt detection methods. Existing detection techniques, both blackbox and whitebox, face challenges related to the diversity of toxic prompts, scalability, and computational efficiency. In response, we propose ToxicDetector, a lightweight greybox method designed to efficiently detect toxic prompts in LLMs. ToxicDetector leverages LLMs to create toxic concept prompts, uses embedding vectors to form feature vectors, and employs a Multi-Layer Perceptron (MLP) classifier for prompt classification. Our evaluation on various versions of the LLama models, Gemma-2, and multiple datasets demonstrates that ToxicDetector achieves a high accuracy of 96.39\% and a low false positive rate of 2.00\%, outperforming state-of-the-art methods. Additionally, ToxicDetector's processing time of 0.0780 seconds per prompt makes it highly suitable for real-time applications. ToxicDetector achieves high accuracy, efficiency, and scalability, making it a practical method for toxic prompt detection in LLMs.

Recent advances in large language models (LLMs) have enabled increasingly capable chatbots. However, most existing systems focus on single-user settings and do not generalize well to multi-user group chats, where agents require more proactive and accurate intervention under complex, evolving contexts. Existing approaches typically rely on LLMs for both reasoning and generation, leading to high token consumption, limited scalability, and potential privacy risks. To address these challenges, we propose GroupGPT, a token-efficient and privacy-preserving agentic framework for multi-user chat assistant. GroupGPT adopts a small-large model collaborative architecture to decouple intervention timing from response generation, enabling efficient and accurate decision-making. The framework also supports multimodal inputs, including memes, images, videos, and voice messages. We further introduce MUIR, a benchmark dataset for multi-user chat assistant intervention reasoning. MUIR contains 2,500 annotated group chat segments with intervention labels and rationales, supporting evaluation of timing accuracy and response quality. We evaluate a range of models on MUIR, from large language models to smaller counterparts. Extensive experiments demonstrate that GroupGPT produces accurate and well-timed responses, achieving an average score of 4.72/5.0 in LLM-based evaluation, and is well received by users across diverse group chat scenarios. Moreover, GroupGPT reduces token usage by up to 3 times compared to baseline methods, while providing privacy sanitization of user messages before cloud transmission. Code is available at: https://github.com/Eliot-Shen/GroupGPT .

We introduce a protein language model for determining the complete sequence of a peptide based on measurement of a limited set of amino acids. To date, protein sequencing relies on mass spectrometry, with some novel edman degregation based platforms able to sequence non-native peptides. Current protein sequencing techniques face limitations in accurately identifying all amino acids, hindering comprehensive proteome analysis. Our method simulates partial sequencing data by selectively masking amino acids that are experimentally difficult to identify in protein sequences from the UniRef database. This targeted masking mimics real-world sequencing limitations. We then modify and finetune a ProtBert derived transformer-based model, for a new downstream task predicting these masked residues, providing an approximation of the complete sequence. Evaluating on three bacterial Escherichia species, we achieve per-amino-acid accuracy up to 90.5% when only four amino acids ([KCYM]) are known. Structural assessment using AlphaFold and TM-score validates the biological relevance of our predictions. The model also demonstrates potential for evolutionary analysis through cross-species performance. This integration of simulated experimental constraints with computational predictions offers a promising avenue for enhancing protein sequence analysis, potentially accelerating advancements in proteomics and structural biology by providing a probabilistic reconstruction of the complete protein sequence from limited experimental data.

This technical paper introduces a chatting robot system that utilizes recent advancements in large-scale language models (LLMs) such as GPT-3 and ChatGPT. The system is integrated with a co-speech gesture generation system, which selects appropriate gestures based on the conceptual meaning of speech. Our motivation is to explore ways of utilizing the recent progress in LLMs for practical robotic applications, which benefits the development of both chatbots and LLMs. Specifically, it enables the development of highly responsive chatbot systems by leveraging LLMs and adds visual effects to the user interface of LLMs as an additional value. The source code for the system is available on GitHub for our in-house robot (https://github.com/microsoft/LabanotationSuite/tree/master/MSRAbotChatSimulation) and GitHub for Toyota HSR (https://github.com/microsoft/GPT-Enabled-HSR-CoSpeechGestures).

Understanding the 3D structures of protein multimers is crucial, as they play a vital role in regulating various cellular processes. It has been empirically confirmed that the multimer structure prediction~(MSP) can be well handled in a step-wise assembly fashion using provided dimer structures and predicted protein-protein interactions~(PPIs). However, due to the biological gap in the formation of dimers and larger multimers, directly applying PPI prediction techniques can often cause a poor generalization to the MSP task. To address this challenge, we aim to extend the PPI knowledge to multimers of different scales~(i.e., chain numbers). Specifically, we propose \textsc{PromptMSP}, a pre-training and Prompt tuning framework for Multimer Structure Prediction. First, we tailor the source and target tasks for effective PPI knowledge learning and efficient inference, respectively. We design PPI-inspired prompt learning to narrow the gaps of two task formats and generalize the PPI knowledge to multimers of different scales. We provide a meta-learning strategy to learn a reliable initialization of the prompt model, enabling our prompting framework to effectively adapt to limited data for large-scale multimers. Empirically, we achieve both significant accuracy (RMSD and TM-Score) and efficiency improvements compared to advanced MSP models. The code, data and checkpoints are released at https://github.com/zqgao22/PromptMSP.

Large Language Models (LLMs), including GPT-x and LLaMA2, have achieved remarkable performance in multiple Natural Language Processing (NLP) tasks. Under the premise that protein sequences constitute the protein language, Protein Large Language Models (ProLLMs) trained on protein corpora excel at de novo protein sequence generation. However, as of now, unlike LLMs in NLP, no ProLLM is capable of multiple tasks in the Protein Language Processing (PLP) field. This prompts us to delineate the inherent limitations in current ProLLMs: (i) the lack of natural language capabilities, (ii) insufficient instruction understanding, and (iii) high training resource demands. To address these challenges, we introduce a training framework to transform any general LLM into a ProLLM capable of handling multiple PLP tasks. Specifically, our framework utilizes low-rank adaptation and employs a two-stage training approach, and it is distinguished by its universality, low overhead, and scalability. Through training under this framework, we propose the ProLLaMA model, the first known ProLLM to handle multiple PLP tasks simultaneously. Experiments show that ProLLaMA achieves state-of-the-art results in the unconditional protein sequence generation task. In the controllable protein sequence generation task, ProLLaMA can design novel proteins with desired functionalities. In the protein property prediction task, ProLLaMA achieves nearly 100\% accuracy across many categories. The latter two tasks are beyond the reach of other ProLLMs. Code is available at https://github.com/Lyu6PosHao/ProLLaMA.

Dialogue systems are a popular natural language processing (NLP) task as it is promising in real-life applications. It is also a complicated task since many NLP tasks deserving study are involved. As a result, a multitude of novel works on this task are carried out, and most of them are deep learning based due to the outstanding performance. In this survey, we mainly focus on the deep learning based dialogue systems. We comprehensively review state-of-the-art research outcomes in dialogue systems and analyze them from two angles: model type and system type. Specifically, from the angle of model type, we discuss the principles, characteristics, and applications of different models that are widely used in dialogue systems. This will help researchers acquaint these models and see how they are applied in state-of-the-art frameworks, which is rather helpful when designing a new dialogue system. From the angle of system type, we discuss task-oriented and open-domain dialogue systems as two streams of research, providing insight into the hot topics related. Furthermore, we comprehensively review the evaluation methods and datasets for dialogue systems to pave the way for future research. Finally, some possible research trends are identified based on the recent research outcomes. To the best of our knowledge, this survey is the most comprehensive and up-to-date one at present for deep learning based dialogue systems, extensively covering the popular techniques. We speculate that this work is a good starting point for academics who are new to the dialogue systems or those who want to quickly grasp up-to-date techniques in this area.

Large Language Models (LLMs), with their flexible generation abilities, can be powerful data sources in domains with few or no available corpora. However, problems like hallucinations and biases limit such applications. In this case study, we pick nutrition counselling, a domain lacking any public resource, and show that high-quality datasets can be gathered by combining LLMs, crowd-workers and nutrition experts. We first crowd-source and cluster a novel dataset of diet-related issues, then work with experts to prompt ChatGPT into producing related supportive text. Finally, we let the experts evaluate the safety of the generated text. We release HAI-coaching, the first expert-annotated nutrition counselling dataset containing ~2.4K dietary struggles from crowd workers, and ~97K related supportive texts generated by ChatGPT. Extensive analysis shows that ChatGPT while producing highly fluent and human-like text, also manifests harmful behaviours, especially in sensitive topics like mental health, making it unsuitable for unsupervised use.

Proteins are essential macromolecules defined by their amino acid sequences, which determine their three-dimensional structures and, consequently, their functions in all living organisms. Therefore, generative protein modeling necessitates a multimodal approach to simultaneously model, understand, and generate both sequences and structures. However, existing methods typically use separate models for each modality, limiting their ability to capture the intricate relationships between sequence and structure. This results in suboptimal performance in tasks that requires joint understanding and generation of both modalities. In this paper, we introduce DPLM-2, a multimodal protein foundation model that extends discrete diffusion protein language model (DPLM) to accommodate both sequences and structures. To enable structural learning with the language model, 3D coordinates are converted to discrete tokens using a lookup-free quantization-based tokenizer. By training on both experimental and high-quality synthetic structures, DPLM-2 learns the joint distribution of sequence and structure, as well as their marginals and conditionals. We also implement an efficient warm-up strategy to exploit the connection between large-scale evolutionary data and structural inductive biases from pre-trained sequence-based protein language models. Empirical evaluation shows that DPLM-2 can simultaneously generate highly compatible amino acid sequences and their corresponding 3D structures eliminating the need for a two-stage generation approach. Moreover, DPLM-2 demonstrates competitive performance in various conditional generation tasks, including folding, inverse folding, and scaffolding with multimodal motif inputs, as well as providing structure-aware representations for predictive tasks.

People are increasingly seeking healthcare information from large language models (LLMs) via interactive chatbots, yet the nature and inherent risks of these conversations remain largely unexplored. In this paper, we filter large-scale conversational AI datasets to achieve HealthChat-11K, a curated dataset of 11K real-world conversations composed of 25K user messages. We use HealthChat-11K and a clinician-driven taxonomy for how users interact with LLMs when seeking healthcare information in order to systematically study user interactions across 21 distinct health specialties. Our analysis reveals insights into the nature of how and why users seek health information, such as common interactions, instances of incomplete context, affective behaviors, and interactions (e.g., leading questions) that can induce sycophancy, underscoring the need for improvements in the healthcare support capabilities of LLMs deployed as conversational AI. Code and artifacts to retrieve our analyses and combine them into a curated dataset can be found here: https://github.com/yahskapar/HealthChat

Applications that could benefit from automatic understanding of human-human conversations often come with challenges associated with private information in real-world data such as call center or clinical conversations. Working with protected data also increases costs of annotation, which limits technology development. To address these challenges, we propose DIALGEN, a human-in-the-loop semi-automated dialogue generation framework. DIALGEN uses a language model (ChatGPT) that can follow schema and style specifications to produce fluent conversational text, generating a complex conversation through iteratively generating subdialogues and using human feedback to correct inconsistencies or redirect the flow. In experiments on structured summarization of agent-client information gathering calls, framed as dialogue state tracking, we show that DIALGEN data enables significant improvement in model performance.

System-prompting is a standard tool for customizing language-model chatbots, enabling them to follow a specific instruction. An implicit assumption in the use of system prompts is that they will be stable, so the chatbot will continue to generate text according to the stipulated instructions for the duration of a conversation. We propose a quantitative benchmark to test this assumption, evaluating instruction stability via self-chats between two instructed chatbots. Testing popular models like LLaMA2-chat-70B and GPT-3.5, we reveal a significant instruction drift within eight rounds of conversations. An empirical and theoretical analysis of this phenomenon suggests the transformer attention mechanism plays a role, due to attention decay over long exchanges. To combat attention decay and instruction drift, we propose a lightweight method called split-softmax, which compares favorably against two strong baselines.

Large language models (LLMs) have demonstrated their significant potential to be applied for addressing various application tasks. However, traditional recommender systems continue to face great challenges such as poor interactivity and explainability, which actually also hinder their broad deployment in real-world systems. To address these limitations, this paper proposes a novel paradigm called Chat-Rec (ChatGPT Augmented Recommender System) that innovatively augments LLMs for building conversational recommender systems by converting user profiles and historical interactions into prompts. Chat-Rec is demonstrated to be effective in learning user preferences and establishing connections between users and products through in-context learning, which also makes the recommendation process more interactive and explainable. What's more, within the Chat-Rec framework, user's preferences can transfer to different products for cross-domain recommendations, and prompt-based injection of information into LLMs can also handle the cold-start scenarios with new items. In our experiments, Chat-Rec effectively improve the results of top-k recommendations and performs better in zero-shot rating prediction task. Chat-Rec offers a novel approach to improving recommender systems and presents new practical scenarios for the implementation of AIGC (AI generated content) in recommender system studies.

The success of language models, especially transformer-based architectures, has trickled into other domains giving rise to "scientific language models" that operate on small molecules, proteins or polymers. In chemistry, language models contribute to accelerating the molecule discovery cycle as evidenced by promising recent findings in early-stage drug discovery. Here, we review the role of language models in molecular discovery, underlining their strength in de novo drug design, property prediction and reaction chemistry. We highlight valuable open-source software assets thus lowering the entry barrier to the field of scientific language modeling. Last, we sketch a vision for future molecular design that combines a chatbot interface with access to computational chemistry tools. Our contribution serves as a valuable resource for researchers, chemists, and AI enthusiasts interested in understanding how language models can and will be used to accelerate chemical discovery.

Multimodal protein language models (PLMs) integrate sequence and token-based structural information, serving as a powerful foundation for protein modeling, generation, and design. However, the reliance on tokenizing 3D structures into discrete tokens causes substantial loss of fidelity about fine-grained structural details and correlations. In this paper, we systematically elucidate the design space of multimodal PLMs to overcome their limitations. We identify tokenization loss and inaccurate structure token predictions by the PLMs as major bottlenecks. To address these, our proposed design space covers improved generative modeling, structure-aware architectures and representation learning, and data exploration. Our advancements approach finer-grained supervision, demonstrating that token-based multimodal PLMs can achieve robust structural modeling. The effective design methods dramatically improve the structure generation diversity, and notably, folding abilities of our 650M model by reducing the RMSD from 5.52 to 2.36 on PDB testset, even outperforming 3B baselines and on par with the specialized folding models.

Traditional dialog systems used in goal-oriented applications require a lot of domain-specific handcrafting, which hinders scaling up to new domains. End-to-end dialog systems, in which all components are trained from the dialogs themselves, escape this limitation. But the encouraging success recently obtained in chit-chat dialog may not carry over to goal-oriented settings. This paper proposes a testbed to break down the strengths and shortcomings of end-to-end dialog systems in goal-oriented applications. Set in the context of restaurant reservation, our tasks require manipulating sentences and symbols, so as to properly conduct conversations, issue API calls and use the outputs of such calls. We show that an end-to-end dialog system based on Memory Networks can reach promising, yet imperfect, performance and learn to perform non-trivial operations. We confirm those results by comparing our system to a hand-crafted slot-filling baseline on data from the second Dialog State Tracking Challenge (Henderson et al., 2014a). We show similar result patterns on data extracted from an online concierge service.

Recent advancements in large language models (LLMs) have provided a new avenue for chatbot development. Most existing research, however, has primarily centered on single-user chatbots that determine "What" to answer. This paper highlights the complexity of multi-user chatbots, introducing the 3W design dimensions: "What" to say, "When" to respond, and "Who" to answer. Additionally, we proposed Multi-User Chat Assistant (MUCA), an LLM-based framework tailored for group discussions. MUCA consists of three main modules: Sub-topic Generator, Dialog Analyzer, and Conversational Strategies Arbitrator. These modules jointly determine suitable response contents, timings, and appropriate addressees. This paper further proposes an LLM-based Multi-User Simulator (MUS) to ease MUCA's optimization, enabling faster simulation of conversations between the chatbot and simulated users, and speeding up MUCA's early development. In goal-oriented conversations with a small to medium number of participants, MUCA demonstrates effectiveness in tasks like chiming in at appropriate timings, generating relevant content, and improving user engagement, as shown by case studies and user studies.

The recent success of large language models (LLMs) has shown great potential to develop more powerful conversational recommender systems (CRSs), which rely on natural language conversations to satisfy user needs. In this paper, we embark on an investigation into the utilization of ChatGPT for conversational recommendation, revealing the inadequacy of the existing evaluation protocol. It might over-emphasize the matching with the ground-truth items or utterances generated by human annotators, while neglecting the interactive nature of being a capable CRS. To overcome the limitation, we further propose an interactive Evaluation approach based on LLMs named iEvaLM that harnesses LLM-based user simulators. Our evaluation approach can simulate various interaction scenarios between users and systems. Through the experiments on two publicly available CRS datasets, we demonstrate notable improvements compared to the prevailing evaluation protocol. Furthermore, we emphasize the evaluation of explainability, and ChatGPT showcases persuasive explanation generation for its recommendations. Our study contributes to a deeper comprehension of the untapped potential of LLMs for CRSs and provides a more flexible and easy-to-use evaluation framework for future research endeavors. The codes and data are publicly available at https://github.com/RUCAIBox/iEvaLM-CRS.

While deep learning has revolutionized the prediction of rigid protein structures, modelling the conformational ensembles of Intrinsically Disordered Proteins (IDPs) remains a key frontier. Current AI paradigms present a trade-off: Protein Language Models (PLMs) capture evolutionary statistics but lack explicit physical grounding, while generative models trained to model full ensembles are computationally expensive. In this work we critically assess these limits and propose a path forward. We introduce GeoGraph, a simulation-informed surrogate trained to predict ensemble-averaged statistics of residue-residue contact-map topology directly from sequence. By featurizing coarse-grained molecular dynamics simulations into residue- and sequence-level graph descriptors, we create a robust and information-rich learning target. Our evaluation demonstrates that this approach yields representations that are more predictive of key biophysical properties than existing methods.

Antibodies are proteins produced by the immune system that can identify and neutralise a wide variety of antigens with high specificity and affinity, and constitute the most successful class of biotherapeutics. With the advent of next-generation sequencing, billions of antibody sequences have been collected in recent years, though their application in the design of better therapeutics has been constrained by the sheer volume and complexity of the data. To address this challenge, we present IgBert and IgT5, the best performing antibody-specific language models developed to date which can consistently handle both paired and unpaired variable region sequences as input. These models are trained comprehensively using the more than two billion unpaired sequences and two million paired sequences of light and heavy chains present in the Observed Antibody Space dataset. We show that our models outperform existing antibody and protein language models on a diverse range of design and regression tasks relevant to antibody engineering. This advancement marks a significant leap forward in leveraging machine learning, large scale data sets and high-performance computing for enhancing antibody design for therapeutic development.

Large language models (LLMs) chatbots like ChatGPT are increasingly used for mental health support. They offer accessible, therapeutic support but also raise concerns about misinformation, over-reliance, and risks in high-stakes contexts of mental health. We crowdsource large-scale users' posts from six major social media platforms to examine how people discuss their interactions with LLM chatbots across different mental health conditions. Through an LLM-assisted pipeline grounded in Value-Sensitive Design (VSD), we mapped the relationships across user-reported sentiments, mental health conditions, perspectives, and values. Our results reveal that the use of LLM chatbots is condition-specific. Users with neurodivergent conditions (e.g., ADHD, ASD) report strong positive sentiments and instrumental or appraisal support, whereas higher-risk disorders (e.g., schizophrenia, bipolar disorder) show more negative sentiments. We further uncover how user perspectives co-occur with underlying values, such as identity, autonomy, and privacy. Finally, we discuss shifting from "one-size-fits-all" chatbot design toward condition-specific, value-sensitive LLM design.

Understanding the relationships between protein sequence, structure and function is a long-standing biological challenge with manifold implications from drug design to our understanding of evolution. Recently, protein language models have emerged as the preferred method for this challenge, thanks to their ability to harness large sequence databases. Yet, their reliance on expansive sequence data and parameter sets limits their flexibility and practicality in real-world scenarios. Concurrently, the recent surge in computationally predicted protein structures unlocks new opportunities in protein representation learning. While promising, the computational burden carried by such complex data still hinders widely-adopted practical applications. To address these limitations, we introduce a novel framework that enhances protein language models by integrating protein structural data. Drawing from recent advances in graph transformers, our approach refines the self-attention mechanisms of pretrained language transformers by integrating structural information with structure extractor modules. This refined model, termed Protein Structure Transformer (PST), is further pretrained on a small protein structure database, using the same masked language modeling objective as traditional protein language models. Empirical evaluations of PST demonstrate its superior parameter efficiency relative to protein language models, despite being pretrained on a dataset comprising only 542K structures. Notably, PST consistently outperforms the state-of-the-art foundation model for protein sequences, ESM-2, setting a new benchmark in protein function prediction. Our findings underscore the potential of integrating structural information into protein language models, paving the way for more effective and efficient protein modeling Code and pretrained models are available at https://github.com/BorgwardtLab/PST.

The chit-chat-based conversational recommendation systems (CRS) provide item recommendations to users through natural language interactions. To better understand user's intentions, external knowledge graphs (KG) have been introduced into chit-chat-based CRS. However, existing chit-chat-based CRS usually generate repetitive item recommendations, and they cannot properly infuse knowledge from KG into CRS to generate informative responses. To remedy these issues, we first reformulate the conversational recommendation task to highlight that the recommended items should be new and possibly interested by users. Then, we propose the Knowledge-Enriched Conversational Recommendation System (KECRS). Specifically, we develop the Bag-of-Entity (BOE) loss and the infusion loss to better integrate KG with CRS for generating more diverse and informative responses. BOE loss provides an additional supervision signal to guide CRS to learn from both human-written utterances and KG. Infusion loss bridges the gap between the word embeddings and entity embeddings by minimizing distances of the same words in these two embeddings. Moreover, we facilitate our study by constructing a high-quality KG, \ie The Movie Domain Knowledge Graph (TMDKG). Experimental results on a large-scale dataset demonstrate that KECRS outperforms state-of-the-art chit-chat-based CRS, in terms of both recommendation accuracy and response generation quality.

Recent Multi-Party Conversation (MPC) models typically rely on graph-based approaches to capture dialogue structures. However, these methods have limitations, such as information loss during the projection of utterances into structural embeddings and constraints in leveraging pre-trained language models directly. In this paper, we propose SS-MPC, a response generation model for MPC that eliminates the need for explicit graph structures. Unlike existing models that depend on graphs to analyze conversation structures, SS-MPC internally encodes the dialogue structure as a sequential input, enabling direct utilization of pre-trained language models. Experimental results show that SS-MPC achieves 15.60\% BLEU-1 and 12.44\% ROUGE-L score, outperforming the current state-of-the-art MPC response generation model by 3.91\%p in BLEU-1 and 0.62\%p in ROUGE-L. Additionally, human evaluation confirms that SS-MPC generates more fluent and accurate responses compared to existing MPC models.

This paper introduces ChatbotManip, a novel dataset for studying manipulation in Chatbots. It contains simulated generated conversations between a chatbot and a (simulated) user, where the chatbot is explicitly asked to showcase manipulation tactics, persuade the user towards some goal, or simply be helpful. We consider a diverse set of chatbot manipulation contexts, from consumer and personal advice to citizen advice and controversial proposition argumentation. Each conversation is annotated by human annotators for both general manipulation and specific manipulation tactics. Our research reveals three key findings. First, Large Language Models (LLMs) can be manipulative when explicitly instructed, with annotators identifying manipulation in approximately 84\% of such conversations. Second, even when only instructed to be ``persuasive'' without explicit manipulation prompts, LLMs frequently default to controversial manipulative strategies, particularly gaslighting and fear enhancement. Third, small fine-tuned open source models, such as BERT+BiLSTM have a performance comparable to zero-shot classification with larger models like Gemini 2.5 pro in detecting manipulation, but are not yet reliable for real-world oversight. Our work provides important insights for AI safety research and highlights the need of addressing manipulation risks as LLMs are increasingly deployed in consumer-facing applications.

Large language models (LLMs) have demonstrated significant success in natural language processing (NLP) tasks and have shown promising results in other domains such as protein sequence generation. However, there remain salient differences between LLMs used for NLP, which effectively handle multiple tasks and are available in small sizes, and protein language models that are often specialized for specific tasks and only exist in larger sizes. In this work, we introduce two small protein language models, based on Llama-3-8B and Phi-3-mini, that are capable of both uncontrollable and controllable protein generation. For the uncontrollable generation task, our best model achieves an average pLDDT score of 69.75, demonstrating robust performance in generating viable protein structures. For the controllable generation task, in which the model generates proteins according to properties specified in the prompt, we achieve a remarkable average TM-Score of 0.84, indicating high structural similarity to target proteins. We chose 10 properties, including six classes of enzymes, to extend the capabilities of prior protein language models. Our approach utilizes the Low-Rank Adaptor (LoRA) technique, reducing trainable parameters to just 4% of the original model size, lowering computational requirements. By using a subset of the UniRef50 dataset and small models, we reduced the overall training time by 70% without compromising performance. Notably, Phi-3-mini reduced trainable parameters by 60%, decreasing training cost by 30% compared to Llama 3. Consequently, Phi-3 achieved a comparable TM-Score of 0.81, demonstrating that smaller models can match the performance of larger ones, like Llama 3. We also demonstrate the deployment of our models on the energy efficient ET-SoC-1 chip, significantly improving the TPS/W by a factor of 3.

Here we show that a Large Language Model (LLM) can serve as a foundation model for a Chemical Language Model (CLM) which performs at or above the level of CLMs trained solely on chemical SMILES string data. Using supervised fine-tuning (SFT) and direct preference optimization (DPO) on the open-source Llama LLM, we demonstrate that we can train an LLM to respond to prompts such as generating molecules with properties of interest to drug development. This overall framework allows an LLM to not just be a chatbot client for chemistry and materials tasks, but can be adapted to speak more directly as a CLM which can generate molecules with user-specified properties.

Machine Learning (ML) models are increasingly used to make critical decisions in real-world applications, yet they have become more complex, making them harder to understand. To this end, researchers have proposed several techniques to explain model predictions. However, practitioners struggle to use these explainability techniques because they often do not know which one to choose and how to interpret the results of the explanations. In this work, we address these challenges by introducing TalkToModel: an interactive dialogue system for explaining machine learning models through conversations. Specifically, TalkToModel comprises of three key components: 1) a natural language interface for engaging in conversations, making ML model explainability highly accessible, 2) a dialogue engine that adapts to any tabular model and dataset, interprets natural language, maps it to appropriate explanations, and generates text responses, and 3) an execution component that constructs the explanations. We carried out extensive quantitative and human subject evaluations of TalkToModel. Overall, we found the conversational system understands user inputs on novel datasets and models with high accuracy, demonstrating the system's capacity to generalize to new situations. In real-world evaluations with humans, 73% of healthcare workers (e.g., doctors and nurses) agreed they would use TalkToModel over baseline point-and-click systems for explainability in a disease prediction task, and 85% of ML professionals agreed TalkToModel was easier to use for computing explanations. Our findings demonstrate that TalkToModel is more effective for model explainability than existing systems, introducing a new category of explainability tools for practitioners. Code & demo released here: https://github.com/dylan-slack/TalkToModel.

Medical dialogue systems (MDSs) aim to assist doctors and patients with a range of professional medical services, i.e., diagnosis, treatment and consultation. The development of MDSs is hindered because of a lack of resources. In particular. (1) there is no dataset with large-scale medical dialogues that covers multiple medical services and contains fine-grained medical labels (i.e., intents, actions, slots, values), and (2) there is no set of established benchmarks for MDSs for multi-domain, multi-service medical dialogues. In this paper, we present ReMeDi, a set of resource for medical dialogues. ReMeDi consists of two parts, the ReMeDi dataset and the ReMeDi benchmarks. The ReMeDi dataset contains 96,965 conversations between doctors and patients, including 1,557 conversations with fine-gained labels. It covers 843 types of diseases, 5,228 medical entities, and 3 specialties of medical services across 40 domains. To the best of our knowledge, the ReMeDi dataset is the only medical dialogue dataset that covers multiple domains and services, and has fine-grained medical labels. The second part of the ReMeDi resources consists of a set of state-of-the-art models for (medical) dialogue generation. The ReMeDi benchmark has the following methods: (1) pretrained models (i.e., BERT-WWM, BERT-MED, GPT2, and MT5) trained, validated, and tested on the ReMeDi dataset, and (2) a self-supervised contrastive learning(SCL) method to expand the ReMeDi dataset and enhance the training of the state-of-the-art pretrained models. We describe the creation of the ReMeDi dataset, the ReMeDi benchmarking methods, and establish experimental results using the ReMeDi benchmarking methods on the ReMeDi dataset for future research to compare against. With this paper, we share the dataset, implementations of the benchmarks, and evaluation scripts.

Protein representation learning is critical for numerous biological tasks. Recently, large transformer-based protein language models (pLMs) pretrained on large scale protein sequences have demonstrated significant success in sequence-based tasks. However, pLMs lack structural context. Conversely, graph neural networks (GNNs) designed to leverage 3D structural information have shown promising generalization in protein-related prediction tasks, but their effectiveness is often constrained by the scarcity of labeled structural data. Recognizing that sequence and structural representations are complementary perspectives of the same protein entity, we propose a multimodal bidirectional hierarchical fusion framework to effectively merge these modalities. Our framework employs attention and gating mechanisms to enable effective interaction between pLMs-generated sequential representations and GNN-extracted structural features, improving information exchange and enhancement across layers of the neural network. This bidirectional and hierarchical (Bi-Hierarchical) fusion approach leverages the strengths of both modalities to capture richer and more comprehensive protein representations. Based on the framework, we further introduce local Bi-Hierarchical Fusion with gating and global Bi-Hierarchical Fusion with multihead self-attention approaches. Our method demonstrates consistent improvements over strong baselines and existing fusion techniques in a variety of protein representation learning benchmarks, including enzyme EC classification, model quality assessment, protein-ligand binding affinity prediction, protein-protein binding site prediction, and B cell epitopes prediction. Our method establishes a new state-of-the-art for multimodal protein representation learning, emphasizing the efficacy of Bi-Hierarchical Fusion in bridging sequence and structural modalities.

Large Language Models (LLMs) have become instrumental across various applications, with the customization of these models to specific scenarios becoming increasingly critical. System message, a fundamental component of LLMs, is consist of carefully crafted instructions that guide the behavior of model to meet intended goals. Despite the recognized potential of system messages to optimize AI-driven solutions, there is a notable absence of a comprehensive benchmark for evaluating how well different LLMs follow these system messages. To fill this gap, we introduce SysBench, a benchmark that systematically analyzes system message following ability in terms of three challenging aspects: constraint complexity, instruction misalignment and multi-turn stability. In order to enable effective evaluation, SysBench constructs multi-turn user conversations covering various interaction relationships, based on six common types of constraints from system messages in real-world scenarios. Our dataset contains 500 system messages from various domains, each paired with 5 turns of user conversations, which have been manually formulated and checked to guarantee high quality. SysBench provides extensive evaluation across various LLMs, measuring their ability to follow specified constraints given in system messages. The results highlight both the strengths and weaknesses of existing models, offering key insights and directions for future research. The open source library SysBench is available at https://github.com/PKU-Baichuan-MLSystemLab/SysBench.

We describe the accurate prediction of ligand-protein interaction (LPI) affinities, also known as drug-target interactions (DTI), with instruction fine-tuned pretrained generative small language models (SLMs). We achieved accurate predictions for a range of affinity values associated with ligand-protein interactions on out-of-sample data in a zero-shot setting. Only the SMILES string of the ligand and the amino acid sequence of the protein were used as the model inputs. Our results demonstrate a clear improvement over machine learning (ML) and free-energy perturbation (FEP+) based methods in accurately predicting a range of ligand-protein interaction affinities, which can be leveraged to further accelerate drug discovery campaigns against challenging therapeutic targets.

Generative protein language models are a natural way to design new proteins with desired functions. However, current models are either difficult to direct to produce a protein from a specific family of interest, or must be trained on a large multiple sequence alignment (MSA) from the specific family of interest, making them unable to benefit from transfer learning across families. To address this, we propose Protein Evolutionary Transformer (PoET), an autoregressive generative model of whole protein families that learns to generate sets of related proteins as sequences-of-sequences across tens of millions of natural protein sequence clusters. PoET can be used as a retrieval-augmented language model to generate and score arbitrary modifications conditioned on any protein family of interest, and can extrapolate from short context lengths to generalize well even for small families. This is enabled by a unique Transformer layer; we model tokens sequentially within sequences while attending between sequences order invariantly, allowing PoET to scale to context lengths beyond those used during training. In extensive experiments on deep mutational scanning datasets, we show that PoET outperforms existing protein language models and evolutionary sequence models for variant function prediction across proteins of all MSA depths. We also demonstrate PoET's ability to controllably generate new protein sequences.

There has been a growing effort to replace hand extraction of data from research papers with automated data extraction based on natural language processing, language models, and recently, large language models (LLMs). Although these methods enable efficient extraction of data from large sets of research papers, they require a significant amount of up-front effort, expertise, and coding. In this work we propose the ChatExtract method that can fully automate very accurate data extraction with minimal initial effort and background, using an advanced conversational LLM. ChatExtract consists of a set of engineered prompts applied to a conversational LLM that both identify sentences with data, extract that data, and assure the data's correctness through a series of follow-up questions. These follow-up questions largely overcome known issues with LLMs providing factually inaccurate responses. ChatExtract can be applied with any conversational LLMs and yields very high quality data extraction. In tests on materials data we find precision and recall both close to 90% from the best conversational LLMs, like ChatGPT-4. We demonstrate that the exceptional performance is enabled by the information retention in a conversational model combined with purposeful redundancy and introducing uncertainty through follow-up prompts. These results suggest that approaches similar to ChatExtract, due to their simplicity, transferability, and accuracy are likely to become powerful tools for data extraction in the near future. Finally, databases for critical cooling rates of metallic glasses and yield strengths of high entropy alloys are developed using ChatExtract.

Modern AI technologies for drug discovery are distributed across heterogeneous platforms-including web applications, desktop environments, and code libraries-leading to fragmented workflows, inconsistent interfaces, and high integration overhead. We present an agentic end-to-end drug design framework that leverages a Large Language Model (LLM) in conjunction with the Model Context Protocol (MCP) to dynamically coordinate access to biochemical databases, modular toolchains, and task-specific AI models. The system integrates four state-of-the-art components: MaSIF (MaSIF-site and MaSIF-seed-search) for geometric deep learning-based identification of protein-protein interaction (PPI) sites, Rosetta for grafting protein fragments onto protein backbones to form mini proteins, ProteinMPNN for amino acid sequences redesign, and AlphaFold3 for near-experimental accuracy in complex structure prediction. Starting from a target structure, the framework supports de novo binder generation via surface analysis, scaffold grafting and pose construction, sequence optimization, and structure prediction. Additionally, by replacing rigid, script-based workflows with a protocol-driven, LLM-coordinated architecture, the framework improves reproducibility, reduces manual overhead, and ensures extensibility, portability, and auditability across the entire drug design process.

There has been an increasing research interest in developing specialized dialogue systems that can offer mental health support. However, gathering large-scale and real-life multi-turn conversations for mental health support poses challenges due to the sensitivity of personal information, as well as the time and cost involved. To address these issues, we introduce the SMILE approach, an inclusive language expansion technique that employs ChatGPT to extend public single-turn dialogues into multi-turn ones. Our research first presents a preliminary exploratory study that validates the effectiveness of the SMILE approach. Furthermore, we conduct a comprehensive and systematic contrastive analysis of datasets generated with and without the SMILE approach, demonstrating that the SMILE method results in a large-scale, diverse, and close-to-real-life multi-turn mental health support conversation corpus, including dialog topics, lexical and semantic features. Finally, we use the collected corpus (SMILECHAT) to develop a more effective dialogue system that offers emotional support and constructive suggestions in multi-turn conversations for mental health support.

Protein language models (PLMs) have advanced computational protein science through large-scale pretraining and scalable architectures. In parallel, reinforcement learning (RL) has broadened exploration and enabled precise multi-objective optimization in protein design. Yet whether RL can push PLMs beyond their pretraining priors to uncover latent sequence-structure-function rules remains unclear. We address this by pairing RL with PLMs across four domains: antimicrobial peptide design, kinase variant optimization, antibody engineering, and inverse folding. Using diverse RL algorithms and model classes, we ask if RL improves sampling efficiency and, more importantly, if it reveals capabilities not captured by supervised learning. Across benchmarks, RL consistently boosts success rates and sample efficiency. Performance follows a three-factor interaction: task headroom, reward fidelity, and policy capacity jointly determine gains. When rewards are accurate and informative, policies have sufficient capacity, and tasks leave room beyond supervised baselines, improvements scale; when rewards are noisy or capacity is constrained, gains saturate despite exploration. This view yields practical guidance for RL in protein design: prioritize reward modeling and calibration before scaling policy size, match algorithm and regularization strength to task difficulty, and allocate capacity where marginal gains are largest. Implementation is available at https://github.com/chq1155/RL-PLM.

Peptides are essential in biological processes and therapeutics. In this study, we introduce Multi-Peptide, an innovative approach that combines transformer-based language models with Graph Neural Networks (GNNs) to predict peptide properties. We combine PeptideBERT, a transformer model tailored for peptide property prediction, with a GNN encoder to capture both sequence-based and structural features. By employing Contrastive Language-Image Pre-training (CLIP), Multi-Peptide aligns embeddings from both modalities into a shared latent space, thereby enhancing the model's predictive accuracy. Evaluations on hemolysis and nonfouling datasets demonstrate Multi-Peptide's robustness, achieving state-of-the-art 86.185% accuracy in hemolysis prediction. This study highlights the potential of multimodal learning in bioinformatics, paving the way for accurate and reliable predictions in peptide-based research and applications.

The parallels between protein sequences and natural language in their sequential structures have inspired the application of large language models (LLMs) to protein understanding. Despite the success of LLMs in NLP, their effectiveness in comprehending protein sequences remains an open question, largely due to the absence of datasets linking protein sequences to descriptive text. Researchers have then attempted to adapt LLMs for protein understanding by integrating a protein sequence encoder with a pre-trained LLM. However, this adaptation raises a fundamental question: "Can LLMs, originally designed for NLP, effectively comprehend protein sequences as a form of language?" Current datasets fall short in addressing this question due to the lack of a direct correlation between protein sequences and corresponding text descriptions, limiting the ability to train and evaluate LLMs for protein understanding effectively. To bridge this gap, we introduce ProteinLMDataset, a dataset specifically designed for further self-supervised pretraining and supervised fine-tuning (SFT) of LLMs to enhance their capability for protein sequence comprehension. Specifically, ProteinLMDataset includes 17.46 billion tokens for pretraining and 893,000 instructions for SFT. Additionally, we present ProteinLMBench, the first benchmark dataset consisting of 944 manually verified multiple-choice questions for assessing the protein understanding capabilities of LLMs. ProteinLMBench incorporates protein-related details and sequences in multiple languages, establishing a new standard for evaluating LLMs' abilities in protein comprehension. The large language model InternLM2-7B, pretrained and fine-tuned on the ProteinLMDataset, outperforms GPT-4 on ProteinLMBench, achieving the highest accuracy score. The dataset and the benchmark are available at https://huggingface.co/datasets/tsynbio/ProteinLMBench.

Perception and expression of emotion are key factors to the success of dialogue systems or conversational agents. However, this problem has not been studied in large-scale conversation generation so far. In this paper, we propose Emotional Chatting Machine (ECM) that can generate appropriate responses not only in content (relevant and grammatical) but also in emotion (emotionally consistent). To the best of our knowledge, this is the first work that addresses the emotion factor in large-scale conversation generation. ECM addresses the factor using three new mechanisms that respectively (1) models the high-level abstraction of emotion expressions by embedding emotion categories, (2) captures the change of implicit internal emotion states, and (3) uses explicit emotion expressions with an external emotion vocabulary. Experiments show that the proposed model can generate responses appropriate not only in content but also in emotion.

Proteins, as essential biomolecules, play a central role in biological processes, including metabolic reactions and DNA replication. Accurate prediction of their properties and functions is crucial in biological applications. Recent development of protein language models (pLMs) with supervised fine tuning provides a promising solution to this problem. However, the fine-tuned model is tailored for particular downstream prediction task, and achieving general-purpose protein understanding remains a challenge. In this paper, we introduce Structure-Enhanced Protein Instruction Tuning (SEPIT) framework to bridge this gap. Our approach integrates a noval structure-aware module into pLMs to inform them with structural knowledge, and then connects these enhanced pLMs to large language models (LLMs) to generate understanding of proteins. In this framework, we propose a novel two-stage instruction tuning pipeline that first establishes a basic understanding of proteins through caption-based instructions and then refines this understanding using a mixture of experts (MoEs) to learn more complex properties and functional information with the same amount of activated parameters. Moreover, we construct the largest and most comprehensive protein instruction dataset to date, which allows us to train and evaluate the general-purpose protein understanding model. Extensive experimental results on open-ended generation and closed-set answer tasks demonstrate the superior performance of SEPIT over both closed-source general LLMs and open-source LLMs trained with protein knowledge.

Over the last few years, large language models (LLMs) have emerged as the most important breakthroughs in natural language processing (NLP) that fundamentally transform research and developments in the field. ChatGPT represents one of the most exciting LLM systems developed recently to showcase impressive skills for language generation and highly attract public attention. Among various exciting applications discovered for ChatGPT in English, the model can process and generate texts for multiple languages due to its multilingual training data. Given the broad adoption of ChatGPT for English in different problems and areas, a natural question is whether ChatGPT can also be applied effectively for other languages or it is necessary to develop more language-specific technologies. The answer to this question requires a thorough evaluation of ChatGPT over multiple tasks with diverse languages and large datasets (i.e., beyond reported anecdotes), which is still missing or limited in current research. Our work aims to fill this gap for the evaluation of ChatGPT and similar LLMs to provide more comprehensive information for multilingual NLP applications. While this work will be an ongoing effort to include additional experiments in the future, our current paper evaluates ChatGPT on 7 different tasks, covering 37 diverse languages with high, medium, low, and extremely low resources. We also focus on the zero-shot learning setting for ChatGPT to improve reproducibility and better simulate the interactions of general users. Compared to the performance of previous models, our extensive experimental results demonstrate a worse performance of ChatGPT for different NLP tasks and languages, calling for further research to develop better models and understanding for multilingual learning.

Studying how people interact with large language models (LLMs) in real-world scenarios is increasingly important due to their widespread use in various applications. In this paper, we introduce LMSYS-Chat-1M, a large-scale dataset containing one million real-world conversations with 25 state-of-the-art LLMs. This dataset is collected from 210K unique IP addresses in the wild on our Vicuna demo and Chatbot Arena website. We offer an overview of the dataset's content, including its curation process, basic statistics, and topic distribution, highlighting its diversity, originality, and scale. We demonstrate its versatility through four use cases: developing content moderation models that perform similarly to GPT-4, building a safety benchmark, training instruction-following models that perform similarly to Vicuna, and creating challenging benchmark questions. We believe that this dataset will serve as a valuable resource for understanding and advancing LLM capabilities. The dataset is publicly available at https://huggingface.co/datasets/lmsys/lmsys-chat-1m.

Interacting with human via high-quality multi-turn dialogues is a key feature of large language models (LLMs). However, human-based evaluation of such capability involves intensive manual labor. This report provides a preliminary evaluation of existing large language models for human-style multi-turn chatting, through an LLM-based approach. We start from real-world human dialogues and keep the very first utterances as the ChatSEED. Then we prompt LLMs to generate a full multi-turn dialogue (tens of utterances) based on the ChatSEED, utterance by utterance. Finally, we adopt state-of-the-art LLMs (GPT-4, \etc) as the judge to evaluate the generated dialogues. With different evaluation protocols, we come to substantially identical conclusions. We find that GPT-4 can generate human-style multi-turn dialogues with impressive quality, significantly outperforms its counterparts. It's difficult for a discriminator to distinguish between GPT-4 generated dialogues and human dialogues. In contrast, other LLMs struggle to generate multi-turn dialogues of satisfactory quality due to poor instruction-following capability, tendency to generate lengthy utterances, or limited general capability. All data and codes will be provided in https://github.com/open-compass/BotChat/ and we hope they can serve as a valuable resource for evaluating multi-turn chatting capabilities of LLMs.

Conversational recommender system is an emerging area that has garnered an increasing interest in the community, especially with the advancements in large language models (LLMs) that enable diverse reasoning over conversational input. Despite the progress, the field has many aspects left to explore. The currently available public datasets for conversational recommendation lack specific user preferences and explanations for recommendations, hindering high-quality recommendations. To address such challenges, we present a novel conversational recommendation dataset named PEARL, synthesized with persona- and knowledge-augmented LLM simulators. We obtain detailed persona and knowledge from real-world reviews and construct a large-scale dataset with over 57k dialogues. Our experimental results demonstrate that utterances in PEARL include more specific user preferences, show expertise in the target domain, and provide recommendations more relevant to the dialogue context than those in prior datasets.

In this paper, we propose MPC (Modular Prompted Chatbot), a new approach for creating high-quality conversational agents without the need for fine-tuning. Our method utilizes pre-trained large language models (LLMs) as individual modules for long-term consistency and flexibility, by using techniques such as few-shot prompting, chain-of-thought (CoT), and external memory. Our human evaluation results show that MPC is on par with fine-tuned chatbot models in open-domain conversations, making it an effective solution for creating consistent and engaging chatbots.

Conversational Recommender System (CRS), which aims to recommend high-quality items to users through interactive conversations, has gained great research interest recently. A CRS is usually composed of a recommendation module and a generation module. In the previous work, these two modules are loosely connected in the model training and are shallowly integrated during inference, where a simple switching or copy mechanism is adopted to incorporate recommended items into generated responses. Moreover, the current end-to-end neural models trained on small crowd-sourcing datasets (e.g., 10K dialogs in the ReDial dataset) tend to overfit and have poor chit-chat ability. In this work, we propose a novel unified framework that integrates recommendation into the dialog (RecInDial) generation by introducing a vocabulary pointer. To tackle the low-resource issue in CRS, we finetune the large-scale pretrained language models to generate fluent and diverse responses, and introduce a knowledge-aware bias learned from an entity-oriented knowledge graph to enhance the recommendation performance. Furthermore, we propose to evaluate the CRS models in an end-to-end manner, which can reflect the overall performance of the entire system rather than the performance of individual modules, compared to the separate evaluations of the two modules used in previous work. Experiments on the benchmark dataset ReDial show our RecInDial model significantly surpasses the state-of-the-art methods. More extensive analyses show the effectiveness of our model.

Conversational recommender systems (CRS) aim to recommend relevant items to users by eliciting user preference through natural language conversation. Prior work often utilizes external knowledge graphs for items' semantic information, a language model for dialogue generation, and a recommendation module for ranking relevant items. This combination of multiple components suffers from a cumbersome training process, and leads to semantic misalignment issues between dialogue generation and item recommendation. In this paper, we represent items in natural language and formulate CRS as a natural language processing task. Accordingly, we leverage the power of pre-trained language models to encode items, understand user intent via conversation, perform item recommendation through semantic matching, and generate dialogues. As a unified model, our PECRS (Parameter-Efficient CRS), can be optimized in a single stage, without relying on non-textual metadata such as a knowledge graph. Experiments on two benchmark CRS datasets, ReDial and INSPIRED, demonstrate the effectiveness of PECRS on recommendation and conversation. Our code is available at: https://github.com/Ravoxsg/efficient_unified_crs.

Therapeutic development is a costly and high-risk endeavor that is often plagued by high failure rates. To address this, we introduce TxGemma, a suite of efficient, generalist large language models (LLMs) capable of therapeutic property prediction as well as interactive reasoning and explainability. Unlike task-specific models, TxGemma synthesizes information from diverse sources, enabling broad application across the therapeutic development pipeline. The suite includes 2B, 9B, and 27B parameter models, fine-tuned from Gemma-2 on a comprehensive dataset of small molecules, proteins, nucleic acids, diseases, and cell lines. Across 66 therapeutic development tasks, TxGemma achieved superior or comparable performance to the state-of-the-art generalist model on 64 (superior on 45), and against state-of-the-art specialist models on 50 (superior on 26). Fine-tuning TxGemma models on therapeutic downstream tasks, such as clinical trial adverse event prediction, requires less training data than fine-tuning base LLMs, making TxGemma suitable for data-limited applications. Beyond these predictive capabilities, TxGemma features conversational models that bridge the gap between general LLMs and specialized property predictors. These allow scientists to interact in natural language, provide mechanistic reasoning for predictions based on molecular structure, and engage in scientific discussions. Building on this, we further introduce Agentic-Tx, a generalist therapeutic agentic system powered by Gemini 2.5 that reasons, acts, manages diverse workflows, and acquires external domain knowledge. Agentic-Tx surpasses prior leading models on the Humanity's Last Exam benchmark (Chemistry & Biology) with 52.3% relative improvement over o3-mini (high) and 26.7% over o3-mini (high) on GPQA (Chemistry) and excels with improvements of 6.3% (ChemBench-Preference) and 2.4% (ChemBench-Mini) over o3-mini (high).

Attention-based models trained on protein sequences have demonstrated incredible success at classification and generation tasks relevant for artificial intelligence-driven protein design. However, we lack a sufficient understanding of how very large-scale models and data play a role in effective protein model development. We introduce a suite of protein language models, named ProGen2, that are scaled up to 6.4B parameters and trained on different sequence datasets drawn from over a billion proteins from genomic, metagenomic, and immune repertoire databases. ProGen2 models show state-of-the-art performance in capturing the distribution of observed evolutionary sequences, generating novel viable sequences, and predicting protein fitness without additional finetuning. As large model sizes and raw numbers of protein sequences continue to become more widely accessible, our results suggest that a growing emphasis needs to be placed on the data distribution provided to a protein sequence model. We release the ProGen2 models and code at https://github.com/salesforce/progen.

Recommender systems are software applications that help users to find items of interest in situations of information overload. Current research often assumes a one-shot interaction paradigm, where the users' preferences are estimated based on past observed behavior and where the presentation of a ranked list of suggestions is the main, one-directional form of user interaction. Conversational recommender systems (CRS) take a different approach and support a richer set of interactions. These interactions can, for example, help to improve the preference elicitation process or allow the user to ask questions about the recommendations and to give feedback. The interest in CRS has significantly increased in the past few years. This development is mainly due to the significant progress in the area of natural language processing, the emergence of new voice-controlled home assistants, and the increased use of chatbot technology. With this paper, we provide a detailed survey of existing approaches to conversational recommendation. We categorize these approaches in various dimensions, e.g., in terms of the supported user intents or the knowledge they use in the background. Moreover, we discuss technological approaches, review how CRS are evaluated, and finally identify a number of gaps that deserve more research in the future.

Conversational systems based on Large Language Models (LLMs), such as ChatGPT, show exceptional proficiency in context understanding and response generation. However, despite their impressive capabilities, they still possess limitations, such as providing randomly-guessed answers to ambiguous queries or failing to refuse users' requests, both of which are considered aspects of a conversational agent's proactivity. This raises the question of whether LLM-based conversational systems are equipped to handle proactive dialogue problems. In this work, we conduct a comprehensive analysis of LLM-based conversational systems, specifically focusing on three aspects of proactive dialogue systems: clarification, target-guided, and non-collaborative dialogues. To trigger the proactivity of LLMs, we propose the Proactive Chain-of-Thought prompting scheme, which augments LLMs with the goal planning capability over descriptive reasoning chains. Empirical findings are discussed to promote future studies on LLM-based proactive dialogue systems.

Existing dialog system models require extensive human annotations and are difficult to generalize to different tasks. The recent success of large pre-trained language models such as BERT and GPT-2 (Devlin et al., 2019; Radford et al., 2019) have suggested the effectiveness of incorporating language priors in down-stream NLP tasks. However, how much pre-trained language models can help dialog response generation is still under exploration. In this paper, we propose a simple, general, and effective framework: Alternating Roles Dialog Model (ARDM). ARDM models each speaker separately and takes advantage of the large pre-trained language model. It requires no supervision from human annotations such as belief states or dialog acts to achieve effective conversations. ARDM outperforms or is on par with state-of-the-art methods on two popular task-oriented dialog datasets: CamRest676 and MultiWOZ. Moreover, we can generalize ARDM to more challenging, non-collaborative tasks such as persuasion. In persuasion tasks, ARDM is capable of generating human-like responses to persuade people to donate to a charity.

There has been growing interest in using neural networks and deep learning techniques to create dialogue systems. Conversational recommendation is an interesting setting for the scientific exploration of dialogue with natural language as the associated discourse involves goal-driven dialogue that often transforms naturally into more free-form chat. This paper provides two contributions. First, until now there has been no publicly available large-scale dataset consisting of real-world dialogues centered around recommendations. To address this issue and to facilitate our exploration here, we have collected ReDial, a dataset consisting of over 10,000 conversations centered around the theme of providing movie recommendations. We make this data available to the community for further research. Second, we use this dataset to explore multiple facets of conversational recommendations. In particular we explore new neural architectures, mechanisms, and methods suitable for composing conversational recommendation systems. Our dataset allows us to systematically probe model sub-components addressing different parts of the overall problem domain ranging from: sentiment analysis and cold-start recommendation generation to detailed aspects of how natural language is used in this setting in the real world. We combine such sub-components into a full-blown dialogue system and examine its behavior.

ChatGPT is a large language model (LLM) created by OpenAI that has been carefully trained on a large amount of data. It has revolutionized the field of natural language processing (NLP) and has pushed the boundaries of LLM capabilities. ChatGPT has played a pivotal role in enabling widespread public interaction with generative artificial intelligence (GAI) on a large scale. It has also sparked research interest in developing similar technologies and investigating their applications and implications. In this paper, our primary goal is to provide a concise survey on the current lines of research on ChatGPT and its evolution. We considered both the glass box and black box views of ChatGPT, encompassing the components and foundational elements of the technology, as well as its applications, impacts, and implications. The glass box approach focuses on understanding the inner workings of the technology, and the black box approach embraces it as a complex system, and thus examines its inputs, outputs, and effects. This paves the way for a comprehensive exploration of the technology and provides a road map for further research and experimentation. We also lay out essential foundational literature on LLMs and GAI in general and their connection with ChatGPT. This overview sheds light on existing and missing research lines in the emerging field of LLMs, benefiting both public users and developers. Furthermore, the paper delves into the broad spectrum of applications and significant concerns in fields such as education, research, healthcare, finance, etc.

Target proteins that lack accessible binding pockets and conformational stability have posed increasing challenges for drug development. Induced proximity strategies, such as PROTACs and molecular glues, have thus gained attention as pharmacological alternatives, but still require small molecule docking at binding pockets for targeted protein degradation (TPD). The computational design of protein-based binders presents unique opportunities to access undruggable targets, but have often relied on stable 3D structures or predictions for effective binder generation. Recently, we have leveraged the expressive latent spaces of protein language models (pLMs) for the prioritization of peptide binders from sequence alone, which we have then fused to E3 ubiquitin ligase domains, creating a CRISPR-analogous TPD system for target proteins. However, our methods rely on training discriminator models for ranking heuristically or unconditionally-derived guide peptides for their target binding capability. In this work, we introduce PepMLM, a purely target sequence-conditioned de novo generator of linear peptide binders. By employing a novel masking strategy that uniquely positions cognate peptide sequences at the terminus of target protein sequences, PepMLM tasks the state-of-the-art ESM-2 pLM to fully reconstruct the binder region, achieving low perplexities matching or improving upon previously-validated peptide-protein sequence pairs. After successful in silico benchmarking with AlphaFold-Multimer, we experimentally verify PepMLM's efficacy via fusion of model-derived peptides to E3 ubiquitin ligase domains, demonstrating endogenous degradation of target substrates in cellular models. In total, PepMLM enables the generative design of candidate binders to any target protein, without the requirement of target structure, empowering downstream programmable proteome editing applications.

ChatGPT is attracting a cross-field interest as it provides a language interface with remarkable conversational competency and reasoning capabilities across many domains. However, since ChatGPT is trained with languages, it is currently not capable of processing or generating images from the visual world. At the same time, Visual Foundation Models, such as Visual Transformers or Stable Diffusion, although showing great visual understanding and generation capabilities, they are only experts on specific tasks with one-round fixed inputs and outputs. To this end, We build a system called Visual ChatGPT, incorporating different Visual Foundation Models, to enable the user to interact with ChatGPT by 1) sending and receiving not only languages but also images 2) providing complex visual questions or visual editing instructions that require the collaboration of multiple AI models with multi-steps. 3) providing feedback and asking for corrected results. We design a series of prompts to inject the visual model information into ChatGPT, considering models of multiple inputs/outputs and models that require visual feedback. Experiments show that Visual ChatGPT opens the door to investigating the visual roles of ChatGPT with the help of Visual Foundation Models. Our system is publicly available at https://github.com/microsoft/visual-chatgpt.

Large language models like ChatGPT have recently demonstrated impressive capabilities in natural language understanding and generation, enabling various applications including translation, essay writing, and chit-chatting. However, there is a concern that they can be misused for malicious purposes, such as fraud or denial-of-service attacks. Therefore, it is crucial to develop methods for detecting whether the party involved in a conversation is a bot or a human. In this paper, we propose a framework named FLAIR, Finding Large language model Authenticity via a single Inquiry and Response, to detect conversational bots in an online manner. Specifically, we target a single question scenario that can effectively differentiate human users from bots. The questions are divided into two categories: those that are easy for humans but difficult for bots (e.g., counting, substitution, positioning, noise filtering, and ASCII art), and those that are easy for bots but difficult for humans (e.g., memorization and computation). Our approach shows different strengths of these questions in their effectiveness, providing a new way for online service providers to protect themselves against nefarious activities and ensure that they are serving real users. We open-sourced our dataset on https://github.com/hongwang600/FLAIR and welcome contributions from the community to enrich such detection datasets.

Despite end-to-end neural systems making significant progress in the last decade for task-oriented as well as chit-chat based dialogue systems, most dialogue systems rely on hybrid approaches which use a combination of rule-based, retrieval and generative approaches for generating a set of ranked responses. Such dialogue systems need to rely on a fallback mechanism to respond to out-of-domain or novel user queries which are not answerable within the scope of the dialog system. While, dialog systems today rely on static and unnatural responses like "I don't know the answer to that question" or "I'm not sure about that", we design a neural approach which generates responses which are contextually aware with the user query as well as say no to the user. Such customized responses provide paraphrasing ability and contextualization as well as improve the interaction with the user and reduce dialogue monotonicity. Our simple approach makes use of rules over dependency parses and a text-to-text transformer fine-tuned on synthetic data of question-response pairs generating highly relevant, grammatical as well as diverse questions. We perform automatic and manual evaluations to demonstrate the efficacy of the system.

In precision medicine, quantitative multi-omic features, topological context, and textual biological knowledge play vital roles in identifying disease-critical signaling pathways and targets. Existing pipelines capture only part of these-numerical omics ignore topological context, text-centric LLMs lack quantitative grounded reasoning, and graph-only models underuse node semantics and the generalization of LLMs-limiting mechanistic interpretability. Although Process Reward Models (PRMs) aim to guide reasoning in LLMs, they remain limited by unreliable intermediate evaluation, and vulnerability to reward hacking with computational cost. These gaps motivate integrating quantitative multi-omic signals, topological structure with node annotations, and literature-scale text via LLMs, using subgraph reasoning as the principle bridge linking numeric evidence, topological knowledge and language context. Therefore, we propose GALAX (Graph Augmented LAnguage model with eXplainability), an innovative framework that integrates pretrained Graph Neural Networks (GNNs) into Large Language Models (LLMs) via reinforcement guided by a Graph Process Reward Model (GPRM), which generates disease-relevant subgraphs in a step-wise manner initiated by an LLM and iteratively evaluated by a pretrained GNN, enabling process-level supervision without explicit intermediate reasoning annotations. As an application, we also introduced Target-QA, a benchmark combining CRISPR-identified targets, multi-omic profiles, and biomedical graph knowledge across diverse cancer cell lines, which enables GNN pretraining for supervising step-wise graph construction and supports long-context reasoning over text-numeric graphs (TNGs), providing a scalable and biologically grounded framework for explainable, reinforcement-guided subgraph reasoning toward reliable and interpretable target and pathway discovery in precision medicine.

Recommendation systems have witnessed significant advancements and have been widely used over the past decades. However, most traditional recommendation methods are task-specific and therefore lack efficient generalization ability. Recently, the emergence of ChatGPT has significantly advanced NLP tasks by enhancing the capabilities of conversational models. Nonetheless, the application of ChatGPT in the recommendation domain has not been thoroughly investigated. In this paper, we employ ChatGPT as a general-purpose recommendation model to explore its potential for transferring extensive linguistic and world knowledge acquired from large-scale corpora to recommendation scenarios. Specifically, we design a set of prompts and evaluate ChatGPT's performance on five recommendation scenarios. Unlike traditional recommendation methods, we do not fine-tune ChatGPT during the entire evaluation process, relying only on the prompts themselves to convert recommendation tasks into natural language tasks. Further, we explore the use of few-shot prompting to inject interaction information that contains user potential interest to help ChatGPT better understand user needs and interests. Comprehensive experimental results on Amazon Beauty dataset show that ChatGPT has achieved promising results in certain tasks and is capable of reaching the baseline level in others. We conduct human evaluations on two explainability-oriented tasks to more accurately evaluate the quality of contents generated by different models. And the human evaluations show ChatGPT can truly understand the provided information and generate clearer and more reasonable results. We hope that our study can inspire researchers to further explore the potential of language models like ChatGPT to improve recommendation performance and contribute to the advancement of the recommendation systems field.

Large language models (LLMs) provide a new way to build chatbots by accepting natural language prompts. Yet, it is unclear how to design prompts to power chatbots to carry on naturalistic conversations while pursuing a given goal, such as collecting self-report data from users. We explore what design factors of prompts can help steer chatbots to talk naturally and collect data reliably. To this aim, we formulated four prompt designs with different structures and personas. Through an online study (N = 48) where participants conversed with chatbots driven by different designs of prompts, we assessed how prompt designs and conversation topics affected the conversation flows and users' perceptions of chatbots. Our chatbots covered 79% of the desired information slots during conversations, and the designs of prompts and topics significantly influenced the conversation flows and the data collection performance. We discuss the opportunities and challenges of building chatbots with LLMs.

Recent AI advances have enabled multi-modal systems to model and translate diverse information spaces. Extending beyond text and vision, we introduce OneProt, a multi-modal AI for proteins that integrates structural, sequence, alignment, and binding site data. Using the ImageBind framework, OneProt aligns the latent spaces of modality encoders along protein sequences. It demonstrates strong performance in retrieval tasks and surpasses state-of-the-art methods in various downstream tasks, including metal ion binding classification, gene-ontology annotation, and enzyme function prediction. This work expands multi-modal capabilities in protein models, paving the way for applications in drug discovery, biocatalytic reaction planning, and protein engineering.

Generalization beyond training data remains a central challenge in machine learning for biology. A common way to enhance generalization is self-supervised pre-training on large datasets. However, aiming to perform well on all possible proteins can limit a model's capacity to excel on any specific one, whereas experimentalists typically need accurate predictions for individual proteins they study, often not covered in training data. To address this limitation, we propose a method that enables self-supervised customization of protein language models to one target protein at a time, on the fly, and without assuming any additional data. We show that our Protein Test-Time Training (ProteinTTT) method consistently enhances generalization across different models, their sizes, and datasets. ProteinTTT improves structure prediction for challenging targets, achieves new state-of-the-art results on protein fitness prediction, and enhances function prediction on two tasks. Through two challenging case studies, we also show that customization via ProteinTTT achieves more accurate antibody-antigen loop modeling and enhances 19% of structures in the Big Fantastic Virus Database, delivering improved predictions where general-purpose AlphaFold2 and ESMFold struggle.