Generalize Drug Response Prediction by Latent Independent Projection for Asymmetric Constrained Domain Generalization

The accurate prediction of drug responses remains a formidable challenge, particularly at the single-cell level and in clinical treatment contexts. Some studies employ transfer learning techniques to predict drug responses in individual cells and patients, but they require access to target-domain data during training, which is often unavailable or only obtainable in future. In this study, we propose a novel domain generalization framework, termed panCancerDR, to address this challenge. We conceptualize each cancer type as a distinct source domain, with its cell lines serving as domain-specific samples. Our primary objective is to extract domain-invariant features from the expression profiles of cell lines across diverse cancer types, thereby generalize the predictive capacity to out-of-distribution samples. To enhance robustness, we introduce a latent independence projection (LIP) module that encourages the encoder to extract informative yet non-redundant features. Also, we propose an asymmetric adaptive clustering constraint, which clusters drug-sensitive samples into a compact group while drives resistant samples dispersed across separate clusters in the latent space. Our empirical experiments demonstrate that panCancerDR effectively learns task-relevant features from diverse source domains, and achieves accurate predictions of drug response for unseen cancer type during training. Furthermore, when evaluated on single-cell and patient-level prediction tasks, our model-trained solely on in vitro cell line data without access to target-domain information-consistently outperforms and matched current state-of-the-art methods. These findings highlights the potential of our method for real-world clinical applications.

Baichuan-Omni-1.5 Technical Report

We introduce Baichuan-Omni-1.5, an omni-modal model that not only has omni-modal understanding capabilities but also provides end-to-end audio generation capabilities. To achieve fluent and high-quality interaction across modalities without compromising the capabilities of any modality, we prioritized optimizing three key aspects. First, we establish a comprehensive data cleaning and synthesis pipeline for multimodal data, obtaining about 500B high-quality data (text, audio, and vision). Second, an audio-tokenizer (Baichuan-Audio-Tokenizer) has been designed to capture both semantic and acoustic information from audio, enabling seamless integration and enhanced compatibility with MLLM. Lastly, we designed a multi-stage training strategy that progressively integrates multimodal alignment and multitask fine-tuning, ensuring effective synergy across all modalities. Baichuan-Omni-1.5 leads contemporary models (including GPT4o-mini and MiniCPM-o 2.6) in terms of comprehensive omni-modal capabilities. Notably, it achieves results comparable to leading models such as Qwen2-VL-72B across various multimodal medical benchmarks.

Computational Protein Science in the Era of Large Language Models (LLMs)

Considering the significance of proteins, computational protein science has always been a critical scientific field, dedicated to revealing knowledge and developing applications within the protein sequence-structure-function paradigm. In the last few decades, Artificial Intelligence (AI) has made significant impacts in computational protein science, leading to notable successes in specific protein modeling tasks. However, those previous AI models still meet limitations, such as the difficulty in comprehending the semantics of protein sequences, and the inability to generalize across a wide range of protein modeling tasks. Recently, LLMs have emerged as a milestone in AI due to their unprecedented language processing & generalization capability. They can promote comprehensive progress in fields rather than solving individual tasks. As a result, researchers have actively introduced LLM techniques in computational protein science, developing protein Language Models (pLMs) that skillfully grasp the foundational knowledge of proteins and can be effectively generalized to solve a diversity of sequence-structure-function reasoning problems. While witnessing prosperous developments, it's necessary to present a systematic overview of computational protein science empowered by LLM techniques. First, we summarize existing pLMs into categories based on their mastered protein knowledge, i.e., underlying sequence patterns, explicit structural and functional information, and external scientific languages. Second, we introduce the utilization and adaptation of pLMs, highlighting their remarkable achievements in promoting protein structure prediction, protein function prediction, and protein design studies. Then, we describe the practical application of pLMs in antibody design, enzyme design, and drug discovery. Finally, we specifically discuss the promising future directions in this fast-growing field.

Reasoning with Graphs: Structuring Implicit Knowledge to Enhance LLMs Reasoning

Large language models (LLMs) have demonstrated remarkable success across a wide range of tasks; however, they still encounter challenges in reasoning tasks that require understanding and inferring relationships between distinct pieces of information within text sequences. This challenge is particularly pronounced in tasks involving multi-step processes, such as logical reasoning and multi-hop question answering, where understanding implicit relationships between entities and leveraging multi-hop connections in the given context are crucial. Graphs, as fundamental data structures, explicitly represent pairwise relationships between entities, thereby offering the potential to enhance LLMs' reasoning capabilities. External graphs have proven effective in supporting LLMs across multiple tasks. However, in many reasoning tasks, no pre-existing graph structure is provided. Can we structure implicit knowledge derived from context into graphs to assist LLMs in reasoning? In this paper, we propose Reasoning with Graphs (RwG) by first constructing explicit graphs from the context and then leveraging these graphs to enhance LLM reasoning performance on reasoning tasks. Extensive experiments demonstrate the effectiveness of the proposed method in improving both logical reasoning and multi-hop question answering tasks.

Learning Cross-Domain Representations for Transferable Drug Perturbations on Single-Cell Transcriptional Responses

Phenotypic drug discovery has attracted widespread attention because of its potential to identify bioactive molecules. Transcriptomic profiling provides a comprehensive reflection of phenotypic changes in cellular responses to external perturbations. In this paper, we propose XTransferCDR, a novel generative framework designed for feature decoupling and transferable representation learning across domains. Given a pair of perturbed expression profiles, our approach decouples the perturbation representations from basal states through domain separation encoders and then cross-transfers them in the latent space. The transferred representations are then used to reconstruct the corresponding perturbed expression profiles via a shared decoder. This cross-transfer constraint effectively promotes the learning of transferable drug perturbation representations. We conducted extensive evaluations of our model on multiple datasets, including single-cell transcriptional responses to drugs and single- and combinatorial genetic perturbations. The experimental results show that XTransferCDR achieved better performance than current state-of-the-art methods, showcasing its potential to advance phenotypic drug discovery.

Unpacking Political Bias in Large Language Models: Insights Across Topic Polarization

Large Language Models (LLMs) have been widely used to generate responses on social topics due to their world knowledge and generative capabilities. Beyond reasoning and generation performance, political bias is an essential issue that warrants attention. Political bias, as a universal phenomenon in human society, may be transferred to LLMs and distort LLMs' behaviors of information acquisition and dissemination with humans, leading to unequal access among different groups of people. To prevent LLMs from reproducing and reinforcing political biases, and to encourage fairer LLM-human interactions, comprehensively examining political bias in popular LLMs becomes urgent and crucial. In this study, we systematically measure the political biases in a wide range of LLMs, using a curated set of questions addressing political bias in various contexts. Our findings reveal distinct patterns in how LLMs respond to political topics. For highly polarized topics, most LLMs exhibit a pronounced left-leaning bias. Conversely, less polarized topics elicit greater consensus, with similar response patterns across different LLMs. Additionally, we analyze how LLM characteristics, including release date, model scale, and region of origin affect political bias. The results indicate political biases evolve with model scale and release date, and are also influenced by regional factors of LLMs.

Ask-Before-Detection: Identifying and Mitigating Conformity Bias in LLM-Powered Error Detector for Math Word Problem Solutions

The rise of large language models (LLMs) offers new opportunities for automatic error detection in education, particularly for math word problems (MWPs). While prior studies demonstrate the promise of LLMs as error detectors, they overlook the presence of multiple valid solutions for a single MWP. Our preliminary analysis reveals a significant performance gap between conventional and alternative solutions in MWPs, a phenomenon we term conformity bias in this work. To mitigate this bias, we introduce the Ask-Before-Detect (AskBD) framework, which generates adaptive reference solutions using LLMs to enhance error detection. Experiments on 200 examples of GSM8K show that AskBD effectively mitigates bias and improves performance, especially when combined with reasoning-enhancing techniques like chain-of-thought prompting.

A Survey of Calibration Process for Black-Box LLMs

Large Language Models (LLMs) demonstrate remarkable performance in semantic understanding and generation, yet accurately assessing their output reliability remains a significant challenge. While numerous studies have explored calibration techniques, they primarily focus on White-Box LLMs with accessible parameters. Black-Box LLMs, despite their superior performance, pose heightened requirements for calibration techniques due to their API-only interaction constraints. Although recent researches have achieved breakthroughs in black-box LLMs calibration, a systematic survey of these methodologies is still lacking. To bridge this gap, we presents the first comprehensive survey on calibration techniques for black-box LLMs. We first define the Calibration Process of LLMs as comprising two interrelated key steps: Confidence Estimation and Calibration. Second, we conduct a systematic review of applicable methods within black-box settings, and provide insights on the unique challenges and connections in implementing these key steps. Furthermore, we explore typical applications of Calibration Process in black-box LLMs and outline promising future research directions, providing new perspectives for enhancing reliability and human-machine alignment. This is our GitHub link: https://github.com/LiangruXie/Calibration-Process-in-Black-Box-LLMs

Dynamic Prompt Allocation and Tuning for Continual Test-Time Adaptation

Continual test-time adaptation (CTTA) has recently emerged to adapt a pre-trained source model to continuously evolving target distributions, which accommodates the dynamic nature of real-world environments. To mitigate the risk of catastrophic forgetting in CTTA, existing methods typically incorporate explicit regularization terms to constrain the variation of model parameters. However, they cannot fundamentally resolve catastrophic forgetting because they rely on a single shared model to adapt across all target domains, which inevitably leads to severe inter-domain interference. In this paper, we introduce learnable domain-specific prompts that guide the model to adapt to corresponding target domains, thereby partially disentangling the parameter space of different domains. In the absence of domain identity for target samples, we propose a novel dynamic Prompt AllocatIon aNd Tuning (PAINT) method, which utilizes a query mechanism to dynamically determine whether the current samples come from a known domain or an unexplored one. For known domains, the corresponding domain-specific prompt is directly selected, while for previously unseen domains, a new prompt is allocated. Prompt tuning is subsequently performed using mutual information maximization along with structural regularization. Extensive experiments on three benchmark datasets demonstrate the effectiveness of our PAINT method for CTTA. We have released our code at https://github.com/Cadezzyr/PAINT.

Mixed Blessing: Class-Wise Embedding guided Instance-Dependent Partial Label Learning

In partial label learning (PLL), every sample is associated with a candidate label set comprising the ground-truth label and several noisy labels. The conventional PLL assumes the noisy labels are randomly generated (instance-independent), while in practical scenarios, the noisy labels are always instance-dependent and are highly related to the sample features, leading to the instance-dependent partial label learning (IDPLL) problem. Instance-dependent noisy label is a double-edged sword. On one side, it may promote model training as the noisy labels can depict the sample to some extent. On the other side, it brings high label ambiguity as the noisy labels are quite undistinguishable from the ground-truth label. To leverage the nuances of IDPLL effectively, for the first time we create class-wise embeddings for each sample, which allow us to explore the relationship of instance-dependent noisy labels, i.e., the class-wise embeddings in the candidate label set should have high similarity, while the class-wise embeddings between the candidate label set and the non-candidate label set should have high dissimilarity. Moreover, to reduce the high label ambiguity, we introduce the concept of class prototypes containing global feature information to disambiguate the candidate label set. Extensive experimental comparisons with twelve methods on six benchmark data sets, including four fine-grained data sets, demonstrate the effectiveness of the proposed method. The code implementation is publicly available at https://github.com/Yangfc-ML/CEL.