arXiv subjects

Ahmadreza Argha

Publications and source records attributed to Ahmadreza Argha.

15 recordsLinked to original sources

arXiv2026

Transcriptomic Models for Immunotherapy Response Prediction Show Limited Cross-cohort Generalisability

Immune checkpoint inhibitors (ICIs) have transformed cancer therapy; yet substantial proportion of patients exhibit intrinsic or acquired resistance, making accurate pre-treatment response prediction a critical unmet need. Transcriptomics-based biomarkers derived from bulk and single-cell RNA sequencing (scRNA-seq) offer a promising avenue for capturing tumour-immune interactions, yet the cross-cohort generalisability of existing prediction models remains unclear.We systematically benchmark nine state-of-the-art transcriptomic ICI response predictors, five bulk RNA-seq-based models (COMPASS, IRNet, NetBio, IKCScore, and TNBC-ICI) and four scRNA-seq-based models (PRECISE, DeepGeneX, Tres and scCURE), using publicly available independent datasets unseen during model development. Overall, predictive performance was modest: bulk RNA-seq models performed at or near chance level across most cohorts, while scRNA-seq models showed only marginal improvements. Pathway-level analyses revealed sparse and inconsistent biomarker signals across models. Although scRNA-seq-based predictors converged on immune-related programs such as allograft rejection, bulk RNA-seq-based models exhibited little reproducible overlap. PRECISE and NetBio identified the most coherent immune-related themes, whereas IRNet predominantly captured metabolic pathways weakly aligned with ICI biology. Together, these findings demonstrate the limited cross-cohort robustness and biological consistency of current transcriptomic ICI prediction models, underscoring the need for improved domain adaptation, standardised preprocessing, and biologically grounded model design.

q-bio.GN↗

arXiv2026

Large Language Model Agents for Evidence Based Genetic Disease Severity Classification

Disease severity classification for genetic conditions is subjective and labor-intensive, creating bottlenecks in genomic screening, where commercial panels vary widely in size and overlap. We developed an autonomous AI agent integrating Reasoning and Acting (ReAct) with Retrieval-Augmented Generation (RAG) to classify 10,211 Human Phenotype Ontology terms. It uses American College of Medical Genetics (ACMG)-endorsed severity guidelines and American College of Obstetricians and Gynecologists (ACOG) quality-of-life criteria to retrieve PubMed literature, generate interpretable reasoning chains, and independently verify claims. At the phenotype level, using expert-curated cohorts, the agent achieved 93.55% accuracy (MCC 0.9237) with 82.6% to 91.4% of claims supported by direct evidence or valid inferences. Gene-level severity was aggregated across 8,738 pairs, identifying 3,283 autosomal recessive pairs with severe or profound presentations. External validation showed 95.2% concordance with Mackenzie's Mission gene list. This system enables standardized panel design by providing reliable, automated classification supported by direct evidence.

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arXiv2026

Harmonised benchmarking of foundation models for single-cell and spatial transcriptomics reveals context-dependent generalisation

Single-cell and spatial foundation models promise transferable biological representations, yet their generality remains largely untested across modalities, biological domains and analytical tasks. We benchmarked six representative models, Nicheformer, CellPLM, scGPT-spatial, GenePT, scELMo and Novae, using a harmonised framework spanning scRNA-seq, spatial transcriptomics and Perturb-seq. We evaluated zero-shot and continually pretrained clustering, supervised annotation, marker-gene concordance and perturbation prediction. Model performance was strongly conditional: expression-trained cell-level transformers best resolved many cell-identity tasks, spatial and graph-aware models better preserved tissue architecture, and language-derived gene embeddings were competitive for selected perturbation-response metrics. No model dominated across tasks, and rankings shifted with modality, preprocessing, tokenisation, biological prior, domain shift and metric choice. This benchmark provides practical guidance for model selection and argues that future models should be judged by biological generalisation, interpretability and perturbation-grounded validity, not by scale or leaderboard performance alone.

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arXiv2026

Beyond Quantity: Trajectory Diversity Scaling for Code Agents

As code large language models (LLMs) evolve into tool-interactive agents via the Model Context Protocol (MCP), their generalization is increasingly limited by low-quality synthetic data and the diminishing returns of quantity scaling. Moreover, quantity-centric scaling exhibits an early bottleneck that underutilizes trajectory data. We propose TDScaling, a Trajectory Diversity Scaling-based data synthesis framework for code agents that scales performance through diversity rather than raw volume. Under a fixed training budget, increasing trajectory diversity yields larger gains than adding more trajectories, improving the performance-cost trade-off for agent training. TDScaling integrates four innovations: (1) a Business Cluster mechanism that captures real-service logical dependencies; (2) a blueprint-driven multi-agent paradigm that enforces trajectory coherence; (3) an adaptive evolution mechanism that steers synthesis toward long-tail scenarios using Domain Entropy, Reasoning Mode Entropy, and Cumulative Action Complexity to prevent mode collapse; and (4) a sandboxed code tool that mitigates catastrophic forgetting of intrinsic coding capabilities. Experiments on general tool-use benchmarks (BFCL, tau^2-Bench) and code agent tasks (RebenchT, CodeCI, BIRD) demonstrate a win-win outcome: TDScaling improves both tool-use generalization and inherent coding proficiency. We plan to release the full codebase and the synthesized dataset (including 30,000+ tool clusters) upon publication.

cs.AI↗

arXiv2026

Structuring Reasoning for Complex Rules Beyond Flat Representations

Large language models (LLMs) face significant challenges when processing complex rule systems, as they typically treat interdependent rules as unstructured textual data rather than as logically organized frameworks. This limitation results in reasoning divergence, where models often overlook critical rule dependencies essential for accurate interpretation. Although existing approaches such as Chain-of-Thought (CoT) reasoning have shown promise, they lack systematic methodologies for structured rule processing and are particularly susceptible to error propagation through sequential reasoning chains. To address these limitations, we propose the Dynamic Adjudication Template (DAT), a novel framework inspired by expert human reasoning processes. DAT structures the inference mechanism into three methodical stages: qualitative analysis, evidence gathering, and adjudication. During the qualitative analysis phase, the model comprehensively evaluates the contextual landscape. The subsequent evidence gathering phase involves the targeted extraction of pertinent information based on predefined template elements ([placeholder]), followed by systematic verification against applicable rules. Finally, in the adjudication phase, the model synthesizes these validated components to formulate a comprehensive judgment. Empirical results demonstrate that DAT consistently outperforms conventional CoT approaches in complex rule-based tasks. Notably, DAT enables smaller language models to match, and in some cases exceed, the performance of significantly larger LLMs, highlighting its efficiency and effectiveness in managing intricate rule systems.

cs.AI↗

arXiv2026

Expanding before Inferring: Enhancing Factuality in Large Language Models through Premature Layers Interpolation

Large Language Models (LLMs) demonstrate remarkable capabilities in text understanding and generation. However, their tendency to produce factually inconsistent outputs, commonly referred to as ''hallucinations'', remains a critical challenge. Existing approaches, such as retrieval-based and inference-time correction methods, primarily address this issue at the input or output level, often overlooking the intrinsic information refinement process and the role of premature layers. Meanwhile, alignment- and fine-tuning-based methods are resource-intensive. In this paper, we propose PLI (Premature Layers Interpolation), a novel, training-free, and plug-and-play intervention designed to enhance factuality. PLI mitigates hallucinations by inserting premature layers formed through mathematical interpolation with adjacent layers. Inspired by stable diffusion and sampling steps, PLI extends the depth of information processing and transmission in LLMs, improving factual coherence. Experiments on four publicly available datasets demonstrate that PLI effectively reduces hallucinations while outperforming existing baselines in most cases. Further analysis suggests that the success of layer interpolation is closely linked to LLMs' internal mechanisms. Our dataset and code are available at https://github.com/CuSO4-Chen/PLI.

cs.CL↗

arXiv2025

RxSafeBench: Identifying Medication Safety Issues of Large Language Models in Simulated Consultation

Numerous medical systems powered by Large Language Models (LLMs) have achieved remarkable progress in diverse healthcare tasks. However, research on their medication safety remains limited due to the lack of real world datasets, constrained by privacy and accessibility issues. Moreover, evaluation of LLMs in realistic clinical consultation settings, particularly regarding medication safety, is still underexplored. To address these gaps, we propose a framework that simulates and evaluates clinical consultations to systematically assess the medication safety capabilities of LLMs. Within this framework, we generate inquiry diagnosis dialogues with embedded medication risks and construct a dedicated medication safety database, RxRisk DB, containing 6,725 contraindications, 28,781 drug interactions, and 14,906 indication-drug pairs. A two-stage filtering strategy ensures clinical realism and professional quality, resulting in the benchmark RxSafeBench with 2,443 high-quality consultation scenarios. We evaluate leading open-source and proprietary LLMs using structured multiple choice questions that test their ability to recommend safe medications under simulated patient contexts. Results show that current LLMs struggle to integrate contraindication and interaction knowledge, especially when risks are implied rather than explicit. Our findings highlight key challenges in ensuring medication safety in LLM-based systems and provide insights into improving reliability through better prompting and task-specific tuning. RxSafeBench offers the first comprehensive benchmark for evaluating medication safety in LLMs, advancing safer and more trustworthy AI-driven clinical decision support.

cs.AI↗

arXiv2025

SemanticST: Spatially Informed Semantic Graph Learning for Clustering, Integration, and Scalable Analysis of Spatial Transcriptomics

Spatial transcriptomics (ST) technologies enable gene expression profiling with spatial resolution, offering unprecedented insights into tissue organization and disease heterogeneity. However, current analysis methods often struggle with noisy data, limited scalability, and inadequate modelling of complex cellular relationships. We present SemanticST, a biologically informed, graph-based deep learning framework that models diverse cellular contexts through multi-semantic graph construction. SemanticST builds multiple context-specific graphs capturing spatial proximity, gene expression similarity, and tissue domain structure, and learns disentangled embeddings for each. These are fused using an attention-inspired strategy to yield a unified, biologically meaningful representation. A community-aware min-cut loss improves robustness over contrastive learning, particularly in sparse ST data. SemanticST supports mini-batch training, making it the first graph neural network scalable to large-scale datasets such as Xenium (500,000 cells). Benchmarking across four platforms (Visium, Slide-seq, Stereo-seq, Xenium) and multiple human and mouse tissues shows consistent 20 percentage gains in ARI, NMI, and trajectory fidelity over DeepST, GraphST, and IRIS. In re-analysis of breast cancer Xenium data, SemanticST revealed rare and clinically significant niches, including triple receptor-positive clusters, spatially distinct DCIS-to-IDC transition zones, and FOXC2 tumour-associated myoepithelial cells, suggesting non-canonical EMT programs with stem-like features. SemanticST thus provides a scalable, interpretable, and biologically grounded framework for spatial transcriptomics analysis, enabling robust discovery across tissue types and diseases, and paving the way for spatially resolved tissue atlases and next-generation precision medicine.

q-bio.GN↗

arXiv2025

Lower Layers Matter: Alleviating Hallucination via Multi-Layer Fusion Contrastive Decoding with Truthfulness Refocused

Large Language Models (LLMs) have demonstrated exceptional performance across various natural language processing tasks. However, they occasionally generate inaccurate and counterfactual outputs, a phenomenon commonly referred to as "hallucinations''. To tackle this issue, recent studies have explored contrastive decoding between the original model and an amateur model with induced hallucination, showing promising results. Nevertheless, this approach can disrupt the original LLM's output distribution due to coarse contrast and simple subtraction operations, potentially leading to errors. In this paper, we introduce a novel contrastive decoding framework, termed LOL (LOwer Layer Matters). Unlike prior methods that focus solely on the final layer, our approach integrates contrastive information from lower layers to enable multi-layer fusion during contrastive decoding. Additionally, we incorporate a truthfulness refocused module that leverages instruction guidance to further improve truthfulness in contrastive decoding. Extensive experiments on four publicly available datasets demonstrate that the LOL framework significantly mitigates hallucination while outperforming existing baselines in most cases. For reproducibility, we will release our code and data upon acceptance.

cs.CL↗

arXiv2025

STORYTELLER: An Enhanced Plot-Planning Framework for Coherent and Cohesive Story Generation

Stories are central to human culture, serving to share ideas, preserve traditions, and foster connections. Automatic story generation, a key advancement in artificial intelligence (AI), offers new possibilities for creating personalized content, exploring creative ideas, and enhancing interactive experiences. However, existing methods struggle to maintain narrative coherence and logical consistency. This disconnect compromises the overall storytelling experience, underscoring the need for substantial improvements. Inspired by human cognitive processes, we introduce Storyteller, a novel approach that systemically improves the coherence and consistency of automatically generated stories. Storyteller introduces a plot node structure based on linguistically grounded subject verb object (SVO) triplets, which capture essential story events and ensure a consistent logical flow. Unlike previous methods, Storyteller integrates two dynamic modules, the STORYLINE and narrative entity knowledge graph (NEKG),that continuously interact with the story generation process. This integration produces structurally sound, cohesive and immersive narratives. Extensive experiments demonstrate that Storyteller significantly outperforms existing approaches, achieving an 84.33% average win rate through human preference evaluation. At the same time, it is also far ahead in other aspects including creativity, coherence, engagement, and relevance.

cs.CL↗

arXiv2025

Interpretable graph-based models on multimodal biomedical data integration: A technical review and benchmarking

Integrating heterogeneous biomedical data including imaging, omics, and clinical records supports accurate diagnosis and personalised care. Graph-based models fuse such non-Euclidean data by capturing spatial and relational structure, yet clinical uptake requires regulator-ready interpretability. We present the first technical survey of interpretable graph based models for multimodal biomedical data, covering 26 studies published between Jan 2019 and Sep 2024. Most target disease classification, notably cancer and rely on static graphs from simple similarity measures, while graph-native explainers are rare; post-hoc methods adapted from non-graph domains such as gradient saliency, and SHAP predominate. We group existing approaches into four interpretability families, outline trends such as graph-in-graph hierarchies, knowledge-graph edges, and dynamic topology learning, and perform a practical benchmark. Using an Alzheimer disease cohort, we compare Sensitivity Analysis, Gradient Saliency, SHAP and Graph Masking. SHAP and Sensitivity Analysis recover the broadest set of known AD pathways and Gene-Ontology terms, whereas Gradient Saliency and Graph Masking surface complementary metabolic and transport signatures. Permutation tests show all four beat random gene sets, but with distinct trade-offs: SHAP and Graph Masking offer deeper biology at higher compute cost, while Gradient Saliency and Sensitivity Analysis are quicker though coarser. We also provide a step-by-step flowchart covering graph construction, explainer choice and resource budgeting to help researchers balance transparency and performance. This review synthesises the state of interpretable graph learning for multimodal medicine, benchmarks leading techniques, and charts future directions, from advanced XAI tools to under-studied diseases, serving as a concise reference for method developers and translational scientists.

q-bio.GN↗

arXiv2025

PersonaMath: Boosting Mathematical Reasoning via Persona-Driven Data Augmentation

While closed-source Large Language Models (LLMs) demonstrate strong mathematical problem-solving abilities, open-source models still face challenges with such tasks. To bridge this gap, we propose a data augmentation approach and introduce PersonaMathQA, a dataset derived from MATH and GSM8K, on which we train the PersonaMath models. Our approach consists of two stages: the first stage focuses on learning from Persona Diversification, and the second stage emphasizes learning from Reflection. In the first stage, we regenerate detailed chain-of-thought (CoT) solutions as instructions using a closed-source LLM and introduce a persona-driven data augmentation technique. This technique innovatively classifies personas based on occupations, significantly enhancing the dataset's diversity and quality. In the second stage, we incorporate reflection to fully leverage more challenging and valuable questions. Evaluation of our PersonaMath models on MATH and GSM8K reveals that the PersonaMath-7B model (based on Qwen2.5-7B) achieves an accuracy of 61.2% on MATH and 87.8% on GSM8K, surpassing all baseline methods and achieving state-of-the-art performance. Notably, our dataset contains only 128.9K data points-merely 32.6% of MetaMathQA and 49.5% of MathInstruct-yet our model outperforms these baselines, demonstrating the high quality and diversity of our dataset, which enables more efficient model training. We open-source the PersonaMathQA dataset, PersonaMath models, and our code for public usage.

cs.CL↗

arXiv2025

xJailbreak: Representation Space Guided Reinforcement Learning for Interpretable LLM Jailbreaking

Safety alignment mechanism are essential for preventing large language models (LLMs) from generating harmful information or unethical content. However, cleverly crafted prompts can bypass these safety measures without accessing the model's internal parameters, a phenomenon known as black-box jailbreak. Existing heuristic black-box attack methods, such as genetic algorithms, suffer from limited effectiveness due to their inherent randomness, while recent reinforcement learning (RL) based methods often lack robust and informative reward signals. To address these challenges, we propose a novel black-box jailbreak method leveraging RL, which optimizes prompt generation by analyzing the embedding proximity between benign and malicious prompts. This approach ensures that the rewritten prompts closely align with the intent of the original prompts while enhancing the attack's effectiveness. Furthermore, we introduce a comprehensive jailbreak evaluation framework incorporating keywords, intent matching, and answer validation to provide a more rigorous and holistic assessment of jailbreak success. Experimental results show the superiority of our approach, achieving state-of-the-art (SOTA) performance on several prominent open and closed-source LLMs, including Qwen2.5-7B-Instruct, Llama3.1-8B-Instruct, and GPT-4o-0806. Our method sets a new benchmark in jailbreak attack effectiveness, highlighting potential vulnerabilities in LLMs. The codebase for this work is available at https://github.com/Aegis1863/xJailbreak.

cs.CL↗

arXiv2024

ETAGE: Enhanced Test Time Adaptation with Integrated Entropy and Gradient Norms for Robust Model Performance

Test time adaptation (TTA) equips deep learning models to handle unseen test data that deviates from the training distribution, even when source data is inaccessible. While traditional TTA methods often rely on entropy as a confidence metric, its effectiveness can be limited, particularly in biased scenarios. Extending existing approaches like the Pseudo Label Probability Difference (PLPD), we introduce ETAGE, a refined TTA method that integrates entropy minimization with gradient norms and PLPD, to enhance sample selection and adaptation. Our method prioritizes samples that are less likely to cause instability by combining high entropy with high gradient norms out of adaptation, thus avoiding the overfitting to noise often observed in previous methods. Extensive experiments on CIFAR-10-C and CIFAR-100-C datasets demonstrate that our approach outperforms existing TTA techniques, particularly in challenging and biased scenarios, leading to more robust and consistent model performance across diverse test scenarios. The codebase for ETAGE is available on https://github.com/afsharshamsi/ETAGE.

cs.LG↗

arXiv2023

Deep Learning in Spatially Resolved Transcriptomics: A Comprehensive Technical View

Spatially resolved transcriptomics (SRT) has evolved rapidly through various technologies, enabling scientists to investigate both morphological contexts and gene expression profiling at single-cell resolution in parallel. SRT data are complex and multi-modal, comprising gene expression matrices, spatial information, and often high-resolution histology images. Because of this complexity and multi-modality, sophisticated computational algorithms are required to accurately analyze SRT data. Most efforts in this domain have been made to utilize conventional machine learning and statistical approaches, exhibiting sub-optimal results due to the complicated nature of SRT datasets. To address these shortcomings, researchers have recently employed deep learning algorithms including various state-of-the-art methods mainly in spatial clustering, spatially variable gene identification, and alignment. While great progress has been made in developing deep learning-based models for SRT data analysis, further improvement is still needed to create more biologically aware models that consider aspects such as phylogeny-aware clustering or the analysis of small histology image patches. Additionally, strategies for batch effect removal, normalization, and handling overdispersion and zero inflation patterns of gene expression are still needed in the analysis of SRT data using deep learning methods. In this paper, we provide a comprehensive overview of these deep learning methods, including their strengths and limitations. We also highlight new frontiers, current challenges, limitations, and open questions in this field. Also, we provide a comprehensive list of all available SRT databases that can be used as an extensive resource for future studies.

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