arXiv subjects

Zhihan Zhou

Publications and source records attributed to Zhihan Zhou.

At least 19 recordsLinked to original sources

arXiv2026

DeepVRegulome: DNABERT-based deep-learning framework for predicting the functional impact of short genomic variants on the human regulome

Whole-genome sequencing (WGS) has revealed numerous non-coding short variants whose functional impacts remain poorly understood. Despite recent advances in deep-learning genomic approaches, accurately predicting and prioritizing clinically relevant mutations in gene regulatory regions remains a major challenge. We developed DeepVRegulome, a computational framework integrating 464 fine-tuned DNABERT models (458 transcription factor, 4 histone mark, and 2 splice site models) trained on ENCODE and GENCODE datasets. The framework pairs these deep learning models with a suite of analytical tools: quantitative variant scoring via log-odds ratios to assess functional impact, attention-based motif analysis to identify disrupted sequence patterns, and survival analysis using Kaplan-Meier and Cox proportional hazards models to link high-impact variants with clinical outcomes. To ensure the framework accurately captures variant effects on baseline binding status, we benchmarked DeepVRegulome against an independent experimental assay of allele-specific transcription factor binding (SNP-SELEX) data and compared its performance to four established variant-effect predictors. The analysis identified 572 splice-disrupting and 9,837 transcription-factor binding site-altering mutations occurring in greater than 10 percentage of glioblastoma samples. Survival analysis linked 1352 mutations and 563 disrupted regulatory regions to patient outcomes, enabling stratification via non-coding mutation signatures. All the code, fine-tuned models, and an interactive data portal are publicly available.

q-bio.GN↗

arXiv2026

Genome-Factory: A Library for Tuning, Deploying, and Interpreting Genomic Foundation Models

We introduce Genome-Factory, the first integrated Python library for tuning, deploying, and interpreting genomic foundation models. Our core contribution is to simplify and unify the workflow for genomic model development: data collection, model tuning, inference, benchmarking, and interpretability. For data collection, Genome-Factory offers an automated pipeline to download genomic sequences and preprocess them. For model tuning, Genome-Factory supports both full and parameter-efficient fine-tuning across diverse genomic models. For inference, Genome-Factory enables both embedding extraction and DNA sequence generation. For benchmarking, we include two existing benchmarks and provide a flexible interface to incorporate additional benchmarks. For interpretability, Genome-Factory introduces an open-source biological interpreter based on a sparse auto-encoder. We validate the utility of Genome-Factory across three dimensions: (i) Compatibility with diverse models and fine-tuning methods; (ii) Benchmarking downstream performance using two open-source benchmarks; (iii) Biological interpretation of learned representations with DNABERT-2. These results highlight its practical value for real-world genomic analysis. GitHub: https://github.com/WeiminWu2000/Genome_Factory.

q-bio.GN↗

arXiv2026

Micro-Macro Retrieval: Reducing Long-Form Hallucination in Large Language Models

Large Language Models (LLMs) achieve impressive performance across many tasks but remain prone to hallucination, especially in long-form generation where redundant retrieved contexts and lengthy reasoning chains amplify factual errors. Recent studies highlight a critical phenomenon: the closer key information appears to the model outputs, the higher the factual accuracy. However, existing retrieval-augmented language models (RALMs) lack effective mechanisms to ensure this proximity - external evidence is injected into reasoning via multi-turn retrieval, but this cannot ensure key information stays close to the outputs. We propose Micro-Macro Retrieval (M2R), a novel retrieve-while-generate framework to fill this gap. At the macro level, M2R retrieves coarse-grained evidence from external sources; at the micro level, it extracts essential results from a key information repository built during reasoning and reuses them while generating answers. This design directly addresses the key-information-to-output proximity bottleneck, effectively reducing hallucination in long-form tasks. M2R is trained with a curriculum learning-based reinforcement learning strategy using customized rule-based rewards, enabling stable acquisition of retrieval and grounding skills. Extensive experiments across different benchmarks demonstrate the effectiveness of M2R, especially in lengthy-context settings.

cs.CL↗

arXiv2025

AncientBench: Towards Comprehensive Evaluation on Excavated and Transmitted Chinese Corpora

Comprehension of ancient texts plays an important role in archaeology and understanding of Chinese history and civilization. The rapid development of large language models needs benchmarks that can evaluate their comprehension of ancient characters. Existing Chinese benchmarks are mostly targeted at modern Chinese and transmitted documents in ancient Chinese, but the part of excavated documents in ancient Chinese is not covered. To meet this need, we propose the AncientBench, which aims to evaluate the comprehension of ancient characters, especially in the scenario of excavated documents. The AncientBench is divided into four dimensions, which correspond to the four competencies of ancient character comprehension: glyph comprehension, pronunciation comprehension, meaning comprehension, and contextual comprehension. The benchmark also contains ten tasks, including radical, phonetic radical, homophone, cloze, translation, and more, providing a comprehensive framework for evaluation. We convened archaeological researchers to conduct experimental evaluations, proposed an ancient model as baseline, and conducted extensive experiments on the currently best-performing large language models. The experimental results reveal the great potential of large language models in ancient textual scenarios as well as the gap with humans. Our research aims to promote the development and application of large language models in the field of archaeology and ancient Chinese language.

cs.CL↗

arXiv2025

Learning to Instruct for Visual Instruction Tuning

We propose L2T, an advancement of visual instruction tuning (VIT). While VIT equips Multimodal LLMs (MLLMs) with promising multimodal capabilities, the current design choices for VIT often result in overfitting and shortcut learning, potentially degrading performance. This gap arises from an overemphasis on instruction-following abilities, while neglecting the proactive understanding of visual information. Inspired by this, L2T adopts a simple yet effective approach by incorporating the loss function into both the instruction and response sequences. It seamlessly expands the training data, and regularizes the MLLMs from overly relying on language priors. Based on this merit, L2T achieves a significant relative improvement of up to 9% on comprehensive multimodal benchmarks, requiring no additional training data and incurring negligible computational overhead. Surprisingly, L2T attains exceptional fundamental visual capabilities, yielding up to an 18% improvement in captioning performance, while simultaneously alleviating hallucination in MLLMs. Github code: https://github.com/Feng-Hong/L2T.

cs.CV↗

arXiv2025

Dual-granularity Sinkhorn Distillation for Enhanced Learning from Long-tailed Noisy Data

Real-world datasets for deep learning frequently suffer from the co-occurring challenges of class imbalance and label noise, hindering model performance. While methods exist for each issue, effectively combining them is non-trivial, as distinguishing genuine tail samples from noisy data proves difficult, often leading to conflicting optimization strategies. This paper presents a novel perspective: instead of primarily developing new complex techniques from scratch, we explore synergistically leveraging well-established, individually 'weak' auxiliary models - specialized for tackling either class imbalance or label noise but not both. This view is motivated by the insight that class imbalance (a distributional-level concern) and label noise (a sample-level concern) operate at different granularities, suggesting that robustness mechanisms for each can in principle offer complementary strengths without conflict. We propose Dual-granularity Sinkhorn Distillation (D-SINK), a novel framework that enhances dual robustness by distilling and integrating complementary insights from such 'weak', single-purpose auxiliary models. Specifically, D-SINK uses an optimal transport-optimized surrogate label allocation to align the target model's sample-level predictions with a noise-robust auxiliary and its class distributions with an imbalance-robust one. Extensive experiments on benchmark datasets demonstrate that D-SINK significantly improves robustness and achieves strong empirical performance in learning from long-tailed noisy data.

cs.LG↗

arXiv2025

Cost-Effective Active Labeling for Data-Efficient Cervical Cell Classification

Information on the number and category of cervical cells is crucial for the diagnosis of cervical cancer. However, existing classification methods capable of automatically measuring this information require the training dataset to be representative, which consumes an expensive or even unaffordable human cost. We herein propose active labeling that enables us to construct a representative training dataset using a much smaller human cost for data-efficient cervical cell classification. This cost-effective method efficiently leverages the classifier's uncertainty on the unlabeled cervical cell images to accurately select images that are most beneficial to label. With a fast estimation of the uncertainty, this new algorithm exhibits its validity and effectiveness in enhancing the representative ability of the constructed training dataset. The extensive empirical results confirm its efficacy again in navigating the usage of human cost, opening the avenue for data-efficient cervical cell classification.

cs.CV↗

arXiv2025

InteChar: A Unified Oracle Bone Character List for Ancient Chinese Language Modeling

Constructing historical language models (LMs) plays a crucial role in aiding archaeological provenance studies and understanding ancient cultures. However, existing resources present major challenges for training effective LMs on historical texts. First, the scarcity of historical language samples renders unsupervised learning approaches based on large text corpora highly inefficient, hindering effective pre-training. Moreover, due to the considerable temporal gap and complex evolution of ancient scripts, the absence of comprehensive character encoding schemes limits the digitization and computational processing of ancient texts, particularly in early Chinese writing. To address these challenges, we introduce InteChar, a unified and extensible character list that integrates unencoded oracle bone characters with traditional and modern Chinese. InteChar enables consistent digitization and representation of historical texts, providing a foundation for robust modeling of ancient scripts. To evaluate the effectiveness of InteChar, we construct the Oracle Corpus Set (OracleCS), an ancient Chinese corpus that combines expert-annotated samples with LLM-assisted data augmentation, centered on Chinese oracle bone inscriptions. Extensive experiments show that models trained with InteChar on OracleCS achieve substantial improvements across various historical language understanding tasks, confirming the effectiveness of our approach and establishing a solid foundation for future research in ancient Chinese NLP.

cs.CL↗

arXiv2025

MathReal: We Keep It Real! A Real Scene Benchmark for Evaluating Math Reasoning in Multimodal Large Language Models

Multimodal Large Language Models (MLLMs) have demonstrated remarkable capabilities in visual mathematical reasoning across various existing benchmarks. However, these benchmarks are predominantly based on clean or processed multimodal inputs, without incorporating the images provided by real-world Kindergarten through 12th grade (K-12) educational users. To address this gap, we introduce MathReal, a meticulously curated dataset comprising 2,000 mathematical questions with images captured by handheld mobile devices in authentic scenarios. Each question is an image, containing the question text and visual element. We systematically classify the real images into three primary categories: image quality degradation, perspective variation, and irrelevant content interference, which are further delineated into 14 subcategories. Additionally, MathReal spans five core knowledge and ability categories, which encompass three question types and are divided into three difficulty levels. To comprehensively evaluate the multimodal mathematical reasoning abilities of state-of-the-art MLLMs in real-world scenarios, we design six experimental settings that enable a systematic analysis of their performance. Through extensive experimentation, we find that the problem-solving abilities of existing MLLMs are significantly challenged in realistic educational contexts. Based on this, we conduct a thorough analysis of their performance and error patterns, providing insights into their recognition, comprehension, and reasoning capabilities, and outlining directions for future improvements. Data and code: https://github.com/junfeng0288/MathReal.

cs.CV↗

arXiv2025

Ancient Script Image Recognition and Processing: A Review

Ancient scripts, e.g., Egyptian hieroglyphs, Oracle Bone Inscriptions, and Ancient Greek inscriptions, serve as vital carriers of human civilization, embedding invaluable historical and cultural information. Automating ancient script image recognition has gained importance, enabling large-scale interpretation and advancing research in archaeology and digital humanities. With the rise of deep learning, this field has progressed rapidly, with numerous script-specific datasets and models proposed. While these scripts vary widely, spanning phonographic systems with limited glyphs to logographic systems with thousands of complex symbols, they share common challenges and methodological overlaps. Moreover, ancient scripts face unique challenges, including imbalanced data distribution and image degradation, which have driven the development of various dedicated methods. This survey provides a comprehensive review of ancient script image recognition methods. We begin by categorizing existing studies based on script types and analyzing respective recognition methods, highlighting both their differences and shared strategies. We then focus on challenges unique to ancient scripts, systematically examining their impact and reviewing recent solutions, including few-shot learning and noise-robust techniques. Finally, we summarize current limitations and outline promising future directions. Our goal is to offer a structured, forward-looking perspective to support ongoing advancements in the recognition, interpretation, and decipherment of ancient scripts.

cs.CV↗

arXiv2025

Fast and Low-Cost Genomic Foundation Models via Outlier Removal

To address the challenge of scarce computational resources in genomic modeling, we introduce GERM, a genomic foundation model with strong compression performance and fast adaptability. GERM improves upon models like DNABERT-2 by eliminating outliers that hinder low-rank adaptation and post-training quantization, enhancing both efficiency and robustness. We replace the vanilla attention layer with an outlier-free mechanism inspired by associative memory models. By removing outliers during both pre-training and fine-tuning, this approach accelerates adaptation, reduces computational costs, and enhances quantization robustness within acceptable loss margins. Additionally, we propose GERM-T, a strategy that employs small-step continual learning within the outlier-free framework, leveraging original checkpoints to avoid retraining from scratch. Empirically, GERM improves fine-tuning performance by 37.98% and quantization by 64.34% over the baseline model. It also reduces average kurtosis by 92.14% and maximum infinity norm by 82.77%. Compared to leading methods, GERM consistently delivers superior performance, offering a practical solution for genomic modeling in resource-constrained settings. Code is available at https://github.com/MAGICS-LAB/GERM.

cs.LG↗

arXiv2024

DNABERT-S: Pioneering Species Differentiation with Species-Aware DNA Embeddings

We introduce DNABERT-S, a tailored genome model that develops species-aware embeddings to naturally cluster and segregate DNA sequences of different species in the embedding space. Differentiating species from genomic sequences (i.e., DNA and RNA) is vital yet challenging, since many real-world species remain uncharacterized, lacking known genomes for reference. Embedding-based methods are therefore used to differentiate species in an unsupervised manner. DNABERT-S builds upon a pre-trained genome foundation model named DNABERT-2. To encourage effective embeddings to error-prone long-read DNA sequences, we introduce Manifold Instance Mixup (MI-Mix), a contrastive objective that mixes the hidden representations of DNA sequences at randomly selected layers and trains the model to recognize and differentiate these mixed proportions at the output layer. We further enhance it with the proposed Curriculum Contrastive Learning (C$^2$LR) strategy. Empirical results on 23 diverse datasets show DNABERT-S's effectiveness, especially in realistic label-scarce scenarios. For example, it identifies twice more species from a mixture of unlabeled genomic sequences, doubles the Adjusted Rand Index (ARI) in species clustering, and outperforms the top baseline's performance in 10-shot species classification with just a 2-shot training. Model, codes, and data are publicly available at \url{https://github.com/MAGICS-LAB/DNABERT_S}.

q-bio.GN↗

arXiv2024

General-Purpose User Modeling with Behavioral Logs: A Snapchat Case Study

Learning general-purpose user representations based on user behavioral logs is an increasingly popular user modeling approach. It benefits from easily available, privacy-friendly yet expressive data, and does not require extensive re-tuning of the upstream user model for different downstream tasks. While this approach has shown promise in search engines and e-commerce applications, its fit for instant messaging platforms, a cornerstone of modern digital communication, remains largely uncharted. We explore this research gap using Snapchat data as a case study. Specifically, we implement a Transformer-based user model with customized training objectives and show that the model can produce high-quality user representations across a broad range of evaluation tasks, among which we introduce three new downstream tasks that concern pivotal topics in user research: user safety, engagement and churn. We also tackle the challenge of efficient extrapolation of long sequences at inference time, by applying a novel positional encoding method.

cs.HC↗

arXiv2024

USE: Dynamic User Modeling with Stateful Sequence Models

User embeddings play a crucial role in user engagement forecasting and personalized services. Recent advances in sequence modeling have sparked interest in learning user embeddings from behavioral data. Yet behavior-based user embedding learning faces the unique challenge of dynamic user modeling. As users continuously interact with the apps, user embeddings should be periodically updated to account for users' recent and long-term behavior patterns. Existing methods highly rely on stateless sequence models that lack memory of historical behavior. They have to either discard historical data and use only the most recent data or reprocess the old and new data jointly. Both cases incur substantial computational overhead. To address this limitation, we introduce User Stateful Embedding (USE). USE generates user embeddings and reflects users' evolving behaviors without the need for exhaustive reprocessing by storing previous model states and revisiting them in the future. Furthermore, we introduce a novel training objective named future W-behavior prediction to transcend the limitations of next-token prediction by forecasting a broader horizon of upcoming user behaviors. By combining it with the Same User Prediction, a contrastive learning-based objective that predicts whether different segments of behavior sequences belong to the same user, we further improve the embeddings' distinctiveness and representativeness. We conducted experiments on 8 downstream tasks using Snapchat users' behavioral logs in both static (i.e., fixed user behavior sequences) and dynamic (i.e., periodically updated user behavior sequences) settings. We demonstrate USE's superior performance over established baselines. The results underscore USE's effectiveness and efficiency in integrating historical and recent user behavior sequences into user embeddings in dynamic user modeling.

cs.SI↗

arXiv2024

DNABERT-2: Efficient Foundation Model and Benchmark For Multi-Species Genome

Decoding the linguistic intricacies of the genome is a crucial problem in biology, and pre-trained foundational models such as DNABERT and Nucleotide Transformer have made significant strides in this area. Existing works have largely hinged on k-mer, fixed-length permutations of A, T, C, and G, as the token of the genome language due to its simplicity. However, we argue that the computation and sample inefficiencies introduced by k-mer tokenization are primary obstacles in developing large genome foundational models. We provide conceptual and empirical insights into genome tokenization, building on which we propose to replace k-mer tokenization with Byte Pair Encoding (BPE), a statistics-based data compression algorithm that constructs tokens by iteratively merging the most frequent co-occurring genome segment in the corpus. We demonstrate that BPE not only overcomes the limitations of k-mer tokenization but also benefits from the computational efficiency of non-overlapping tokenization. Based on these insights, we introduce DNABERT-2, a refined genome foundation model that adapts an efficient tokenizer and employs multiple strategies to overcome input length constraints, reduce time and memory expenditure, and enhance model capability. Furthermore, we identify the absence of a comprehensive and standardized benchmark for genome understanding as another significant impediment to fair comparative analysis. In response, we propose the Genome Understanding Evaluation (GUE), a comprehensive multi-species genome classification dataset that amalgamates $36$ distinct datasets across $9$ tasks, with input lengths ranging from $70$ to $10000$. Through comprehensive experiments on the GUE benchmark, we demonstrate that DNABERT-2 achieves comparable performance to the state-of-the-art model with $21 \times$ fewer parameters and approximately $92 \times$ less GPU time in pre-training.

q-bio.GN↗

arXiv2023

Combating Representation Learning Disparity with Geometric Harmonization

Self-supervised learning (SSL) as an effective paradigm of representation learning has achieved tremendous success on various curated datasets in diverse scenarios. Nevertheless, when facing the long-tailed distribution in real-world applications, it is still hard for existing methods to capture transferable and robust representation. Conventional SSL methods, pursuing sample-level uniformity, easily leads to representation learning disparity where head classes dominate the feature regime but tail classes passively collapse. To address this problem, we propose a novel Geometric Harmonization (GH) method to encourage category-level uniformity in representation learning, which is more benign to the minority and almost does not hurt the majority under long-tailed distribution. Specially, GH measures the population statistics of the embedding space on top of self-supervised learning, and then infer an fine-grained instance-wise calibration to constrain the space expansion of head classes and avoid the passive collapse of tail classes. Our proposal does not alter the setting of SSL and can be easily integrated into existing methods in a low-cost manner. Extensive results on a range of benchmark datasets show the effectiveness of GH with high tolerance to the distribution skewness. Our code is available at https://github.com/MediaBrain-SJTU/Geometric-Harmonization.

cs.LG↗

arXiv2023

Efficient Action Robust Reinforcement Learning with Probabilistic Policy Execution Uncertainty

Robust reinforcement learning (RL) aims to find a policy that optimizes the worst-case performance in the face of uncertainties. In this paper, we focus on action robust RL with the probabilistic policy execution uncertainty, in which, instead of always carrying out the action specified by the policy, the agent will take the action specified by the policy with probability $1-ρ$ and an alternative adversarial action with probability $ρ$. We establish the existence of an optimal policy on the action robust MDPs with probabilistic policy execution uncertainty and provide the action robust Bellman optimality equation for its solution. Furthermore, we develop Action Robust Reinforcement Learning with Certificates (ARRLC) algorithm that achieves minimax optimal regret and sample complexity. Furthermore, we conduct numerical experiments to validate our approach's robustness, demonstrating that ARRLC outperforms non-robust RL algorithms and converges faster than the robust TD algorithm in the presence of action perturbations.

cs.LG↗

arXiv2023

KGML-xDTD: A Knowledge Graph-based Machine Learning Framework for Drug Treatment Prediction and Mechanism Description

Background: Computational drug repurposing is a cost- and time-efficient approach that aims to identify new therapeutic targets or diseases (indications) of existing drugs/compounds. It is especially critical for emerging and/or orphan diseases due to its cheaper investment and shorter research cycle compared with traditional wet-lab drug discovery approaches. However, the underlying mechanisms of action (MOAs) between repurposed drugs and their target diseases remain largely unknown, which is still a main obstacle for computational drug repurposing methods to be widely adopted in clinical settings. Results: In this work, we propose KGML-xDTD: a Knowledge Graph-based Machine Learning framework for explainably predicting Drugs Treating Diseases. It is a two-module framework that not only predicts the treatment probabilities between drugs/compounds and diseases but also biologically explains them via knowledge graph (KG) path-based, testable mechanisms of action (MOAs). We leverage knowledge-and-publication based information to extract biologically meaningful "demonstration paths" as the intermediate guidance in the Graph-based Reinforcement Learning (GRL) path-finding process. Comprehensive experiments and case study analyses show that the proposed framework can achieve state-of-the-art performance in both predictions of drug repurposing and recapitulation of human-curated drug MOA paths. Conclusions: KGML-xDTD is the first model framework that can offer KG-path explanations for drug repurposing predictions by leveraging the combination of prediction outcomes and existing biological knowledge and publications. We believe it can effectively reduce "black-box" concerns and increase prediction confidence for drug repurposing based on predicted path-based explanations, and further accelerate the process of drug discovery for emerging diseases.

q-bio.QM↗