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Licheng Zong

Publications and source records attributed to Licheng Zong.

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Search-R2: Enhancing Search-Integrated Reasoning via Actor-Refiner Collaboration

Search-integrated reasoning enables language agents to transcend static parametric knowledge by actively querying external sources. However, training these agents via reinforcement learning is hindered by the multi-scale credit assignment problem: existing methods typically rely on sparse, trajectory-level rewards that fail to distinguish between high-quality reasoning and fortuitous guesses, leading to redundant or misleading search behaviors. To address this, we propose Search-R2, a novel Actor-Refiner collaboration framework that enhances reasoning through targeted intervention, with both components jointly optimized during training. Our approach decomposes the generation process into an Actor, which produces initial reasoning trajectories, and a Meta-Refiner, which selectively diagnoses and repairs flawed steps via a 'cut-and-regenerate' mechanism. To provide fine-grained supervision, we introduce a hybrid reward design that couples outcome correctness with a dense process reward quantifying the information density of retrieved evidence. Theoretically, we formalize the Actor-Refiner interaction as a smoothed mixture policy, proving that selective correction yields strict performance gains over strong baselines. Extensive experiments across various general and multi-hop QA datasets demonstrate that Search-R2 consistently outperforms strong RAG and RL-based baselines across model scales, achieving superior reasoning accuracy with minimal overhead.

cs.AI

Benchmarking Large Language Models on Multiple Tasks in Bioinformatics NLP with Prompting

Large language models (LLMs) have become important tools in solving biological problems, offering improvements in accuracy and adaptability over conventional methods. Several benchmarks have been proposed to evaluate the performance of these LLMs. However, current benchmarks can hardly evaluate the performance of these models across diverse tasks effectively. In this paper, we introduce a comprehensive prompting-based benchmarking framework, termed Bio-benchmark, which includes 30 key bioinformatics tasks covering areas such as proteins, RNA, drugs, electronic health records, and traditional Chinese medicine. Using this benchmark, we evaluate six mainstream LLMs, including GPT-4o and Llama-3.1-70b, etc., using 0-shot and few-shot Chain-of-Thought (CoT) settings without fine-tuning to reveal their intrinsic capabilities. To improve the efficiency of our evaluations, we demonstrate BioFinder, a new tool for extracting answers from LLM responses, which increases extraction accuracy by round 30% compared to existing methods. Our benchmark results show the biological tasks suitable for current LLMs and identify specific areas requiring enhancement. Furthermore, we propose targeted prompt engineering strategies for optimizing LLM performance in these contexts. Based on these findings, we provide recommendations for the development of more robust LLMs tailored for various biological applications. This work offers a comprehensive evaluation framework and robust tools to support the application of LLMs in bioinformatics.

cs.CL

SeRTS: Self-Rewarding Tree Search for Biomedical Retrieval-Augmented Generation

Large Language Models (LLMs) have shown great potential in the biomedical domain with the advancement of retrieval-augmented generation (RAG). However, existing retrieval-augmented approaches face challenges in addressing diverse queries and documents, particularly for medical knowledge queries, resulting in sub-optimal performance. To address these limitations, we propose a novel plug-and-play LLM-based retrieval method called Self-Rewarding Tree Search (SeRTS) based on Monte Carlo Tree Search (MCTS) and a self-rewarding paradigm. By combining the reasoning capabilities of LLMs with the effectiveness of tree search, SeRTS boosts the zero-shot performance of retrieving high-quality and informative results for RAG. We further enhance retrieval performance by fine-tuning LLMs with Proximal Policy Optimization (PPO) objectives using the trajectories collected by SeRTS as feedback. Controlled experiments using the BioASQ-QA dataset with GPT-3.5-Turbo and LLama2-7b demonstrate that our method significantly improves the performance of the BM25 retriever and surpasses the strong baseline of self-reflection in both efficiency and scalability. Moreover, SeRTS generates higher-quality feedback for PPO training than self-reflection. Our proposed method effectively adapts LLMs to document retrieval tasks, enhancing their ability to retrieve highly relevant documents for RAG in the context of medical knowledge queries. This work presents a significant step forward in leveraging LLMs for accurate and comprehensive biomedical question answering.

cs.CL

ProNet DB: A proteome-wise database for protein surface property representations and RNA-binding profiles

The rapid growth in the number of experimental and predicted protein structures and more complicated protein structures challenge users in computational biology for utilizing the structural information and protein surface property representation. Recently, AlphaFold2 released the comprehensive proteome of various species, and protein surface property representation plays a crucial role in protein-molecule interaction prediction such as protein-protein interaction, protein-nucleic acid interaction, and protein-compound interaction. Here, we proposed the first comprehensive database, namely ProNet DB, which incorporates multiple protein surface representations and RNA-binding landscape for more than 326,175 protein structures covering 16 model organism proteomes from AlphaFold Protein Structure Database (AlphaFold DB) and experimentally validated protein structures deposited in Protein Data Bank (PDB). For each protein, we provided the original protein structure, surface property representation including hydrophobicity, charge distribution, hydrogen bond, interacting face, and RNA-binding landscape such as RNA binding sites and RNA binding preference. To interpret protein surface property representation and RNA binding landscape intuitively, we also integrate Mol* and Online 3D Viewer to visualize the representation on the protein surface. The pre-computed features are available for the users instantaneously and boost computational biology development including molecular mechanism exploration, geometry-based drug discovery and novel therapeutics development. The server is now available on https://proj.cse.cuhk.edu.hk/aihlab/pronet/.

q-bio.QM

Interpretable RNA Foundation Model from Unannotated Data for Highly Accurate RNA Structure and Function Predictions

Non-coding RNA structure and function are essential to understanding various biological processes, such as cell signaling, gene expression, and post-transcriptional regulations. These are all among the core problems in the RNA field. With the rapid growth of sequencing technology, we have accumulated a massive amount of unannotated RNA sequences. On the other hand, expensive experimental observatory results in only limited numbers of annotated data and 3D structures. Hence, it is still challenging to design computational methods for predicting their structures and functions. The lack of annotated data and systematic study causes inferior performance. To resolve the issue, we propose a novel RNA foundation model (RNA-FM) to take advantage of all the 23 million non-coding RNA sequences through self-supervised learning. Within this approach, we discover that the pre-trained RNA-FM could infer sequential and evolutionary information of non-coding RNAs without using any labels. Furthermore, we demonstrate RNA-FM's effectiveness by applying it to the downstream secondary/3D structure prediction, SARS-CoV-2 genome structure and evolution prediction, protein-RNA binding preference modeling, and gene expression regulation modeling. The comprehensive experiments show that the proposed method improves the RNA structural and functional modelling results significantly and consistently. Despite only being trained with unlabelled data, RNA-FM can serve as the foundational model for the field.

q-bio.QM

Protein-RNA interaction prediction with deep learning: Structure matters

Protein-RNA interactions are of vital importance to a variety of cellular activities. Both experimental and computational techniques have been developed to study the interactions. Due to the limitation of the previous database, especially the lack of protein structure data, most of the existing computational methods rely heavily on the sequence data, with only a small portion of the methods utilizing the structural information. Recently, AlphaFold has revolutionized the entire protein and biology field. Foreseeably, the protein-RNA interaction prediction will also be promoted significantly in the upcoming years. In this work, we give a thorough review of this field, surveying both the binding site and binding preference prediction problems and covering the commonly used datasets, features, and models. We also point out the potential challenges and opportunities in this field. This survey summarizes the development of the RBP-RNA interaction field in the past and foresees its future development in the post-AlphaFold era.

q-bio.BM

HMD-AMP: Protein Language-Powered Hierarchical Multi-label Deep Forest for Annotating Antimicrobial Peptides

Identifying the targets of an antimicrobial peptide is a fundamental step in studying the innate immune response and combating antibiotic resistance, and more broadly, precision medicine and public health. There have been extensive studies on the statistical and computational approaches to identify (i) whether a peptide is an antimicrobial peptide (AMP) or a non-AMP and (ii) which targets are these sequences effective to (Gram-positive, Gram-negative, etc.). Despite the existing deep learning methods on this problem, most of them are unable to handle the small AMP classes (anti-insect, anti-parasite, etc.). And more importantly, some AMPs can have multiple targets, which the previous methods fail to consider. In this study, we build a diverse and comprehensive multi-label protein sequence database by collecting and cleaning amino acids from various AMP databases. To generate efficient representations and features for the small classes dataset, we take advantage of a protein language model trained on 250 million protein sequences. Based on that, we develop an end-to-end hierarchical multi-label deep forest framework, HMD-AMP, to annotate AMP comprehensively. After identifying an AMP, it further predicts what targets the AMP can effectively kill from eleven available classes. Extensive experiments suggest that our framework outperforms state-of-the-art models in both the binary classification task and the multi-label classification task, especially on the minor classes.The model is robust against reduced features and small perturbations and produces promising results. We believe HMD-AMP contributes to both the future wet-lab investigations of the innate structural properties of different antimicrobial peptides and build promising empirical underpinnings for precise medicine with antibiotics.

cs.LG

Model Adaption Object Detection System for Robot

Object detection for robot guidance is a crucial mission for autonomous robots, which has provoked extensive attention for researchers. However, the changing view of robot movement and limited available data hinder the research in this area. To address these matters, we proposed a new vision system for robots, the model adaptation object detection system. Instead of using a single one to solve problems, We made use of different object detection neural networks to guide the robot in accordance with various situations, with the help of a meta neural network to allocate the object detection neural networks. Furthermore, taking advantage of transfer learning technology and depthwise separable convolutions, our model is easy to train and can address small dataset problems.

cs.CV