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Received — 27 May 2026 ⏭

Interpreting Omics Data Analysis with Large Language Models for Disease Target and Drug Discovery

✇(Multiomics OR Omics) AND (Pancreatic)
By: Zixi Xu · Weihang Chen · Wuyu Ren · Tianqi Xu · Somadina Amaechina · Raad Khan · Yixin Chen · Michael Province · Philip Payne · Fuhai Li
18 May 2026 at 18:00

bioRxiv [Preprint]. 2026 May 5:2026.04.30.721768. doi: 10.64898/2026.04.30.721768.

ABSTRACT

In biomedical scientific discovery, synthesizing prior knowledge from the literature is an essential component of interpreting numerical omics data analyses for disease target identification and drug discovery. Large language models (LLMs) alone can rapidly retrieve disease mechanisms from biomedical text, but text-only outputs are general and unreliable for target and drug prioritization without cohort-specific quantitative evidence. Herein, we propose a provenance-aware Text-to-Target framework that couples schema-constrained multi-model LLM retrieval with numeric omics data analysis. The key design is a modality-aware fusion step: candidates are partitioned into overlap-supported anchors, retrieval-only hidden hubs, and network-emergent novelty nodes, then propagated into staged hypothesis and strategy generation under topology constraints. We evaluate the model in Alzheimer's disease (AD) and pancreatic ductal adenocarcinoma (PDAC). In PDAC, the workflow produced a balanced 75-gene candidate universe and a 23-strategy portfolio, with significant DepMap support at both target level and strategy level. In AD, stricter candidate controls yielded a compact 34-gene universe and 14 strategies; under an expanded CRISPRbrain registry, both target-level axes were significant, with strong strategy-level enrichment. Across both diseases, final strategies preserved full provenance closure to the candidate pool, enabling end-to-end auditability from retrieval artifacts to validation outputs. These results support a transferable discovery architecture in which omics evidence constrains biological activity, LLM retrieval expands mechanistic search space, and network-aware fusion preserves interpretability. The framework provides a reproducible basis for dual-disease target prioritization and motivates continuous literature-mechanism concordance with agentic evidence-refresh loops.

PMID:42146439 | PMC:PMC13174328 | DOI:10.64898/2026.04.30.721768

GPNMB Drives Brain Metastasis by Sculpting a Pathological Endothelial-Immune Interactome

✇Omics In Lung
By: Xuefei Liu · Jun Tan · Chun Wu · Guanyin Huang · Yixin Cheng · Jianyang Hu · Binyu Zhang · Mao Zhao · Boxi Zhao · Jingru Lian · Shuqian Zheng · Lin Zeng · Meng Xu · Yang Xu · Shan Zeng · Hao Yu · Hui Yang · Zhixiang Zuo · Chuanyu Liu · Weineng Feng · Weinan Guo · Chunying Li · Sai-Lan Liu · Qing Liu · Feiqiu Wen · Xin Hong
13 April 2026 at 18:00

Cancer Discov. 2026 Apr 15. doi: 10.1158/2159-8290.CD-25-1663. Online ahead of print.

ABSTRACT

Brain metastases (BM) remain a devastating disease with dismal prognosis. How circulating tumor cells (CTCs) penetrate the blood brain barrier (BBB) and reprogram the brain microenvironment remain unclear. Using spatially resolved multi-omic profiling of CTCs and brain metastases, integrated with experimental and clinical analyses, we identified Glycoprotein Non-Metastatic Melanoma Protein B (GPNMB) as a CTC-secreted driver of vascular disruption and brain colonization. CBX3 upregulation induced GPNMB expression, which bound endothelial EGFR, triggering CBL-mediated ubiquitination and degradation. Attenuated EGFR signaling suppressed FTO and disrupted endothelial junctions via YTHDF2-dependent TJP1 m6A methylation. Remarkably, GPNMB-induced BBB remodeling promoted immune infiltration via CXCL12-CXCR4 axis, and induced time course-dependent T cell exhaustion within the brain microenvironment. Clinically, elevated CBX3⁺GPNMB⁺ CTCs and plasma CXCL12 were significantly associated with BM progression in lung cancer and melanoma. Therapeutically, dual blockade of GPNMB and PD1 enhanced anti-BM efficacy in mice, unveiling GPNMB as a promising target for precision immunotherapy.

PMID:41973996 | DOI:10.1158/2159-8290.CD-25-1663

Received — 4 April 2026 ⏭

SHOE: Semantic HOI Open-Vocabulary Evaluation Metric

✇cs.AI, q-bio.NC updates on arXiv.org
By: Maja Noack · Qinqian Lei · Taipeng Tian · Bihan Dong · Robby T. Tan · Yixin Chen · John Young · Saijun Zhang · Bo Wang
3 April 2026 at 12:00
arXiv:2604.01586v1 Announce Type: cross Abstract: Open-vocabulary human-object interaction (HOI) detection is a step towards building scalable systems that generalize to unseen interactions in real-world scenarios and support grounded multimodal systems that reason about human-object relationships. However, standard evaluation metrics, such as mean Average Precision (mAP), treat HOI classes as discrete categorical labels and fail to credit semantically valid but lexically different predictions (e.g., "lean on couch" vs. "sit on couch"), limiting their applicability for evaluating open-vocabulary predictions that go beyond any predefined set of HOI labels. We introduce SHOE (Semantic HOI Open-Vocabulary Evaluation), a new evaluation framework that incorporates semantic similarity between predicted and ground-truth HOI labels. SHOE decomposes each HOI prediction into its verb and object components, estimates their semantic similarity using the average of multiple large language models (LLMs), and combines them into a similarity score to evaluate alignment beyond exact string match. This enables a flexible and scalable evaluation of both existing HOI detection methods and open-ended generative models using standard benchmarks such as HICO-DET. Experimental results show that SHOE scores align more closely with human judgments than existing metrics, including LLM-based and embedding-based baselines, achieving an agreement of 85.73% with the average human ratings. Our work underscores the need for semantically grounded HOI evaluation that better mirrors human understanding of interactions. We will release our evaluation metric to the public to facilitate future research.

Lifting Unlabeled Internet-level Data for 3D Scene Understanding

✇cs.AI, q-bio.NC updates on arXiv.org
By: Yixin Chen · Yaowei Zhang · Huangyue Yu · Junchao He · Yan Wang · Jiangyong Huang · Hongyu Shen · Junfeng Ni · Shaofei Wang · Baoxiong Jia · Song-Chun Zhu · Siyuan Huang
3 April 2026 at 12:00
arXiv:2604.01907v1 Announce Type: cross Abstract: Annotated 3D scene data is scarce and expensive to acquire, while abundant unlabeled videos are readily available on the internet. In this paper, we demonstrate that carefully designed data engines can leverage web-curated, unlabeled videos to automatically generate training data, to facilitate end-to-end models in 3D scene understanding alongside human-annotated datasets. We identify and analyze bottlenecks in automated data generation, revealing critical factors that determine the efficiency and effectiveness of learning from unlabeled data. To validate our approach across different perception granularities, we evaluate on three tasks spanning low-level perception, i.e., 3D object detection and instance segmentation, to high-evel reasoning, i.e., 3D spatial Visual Question Answering (VQA) and Vision-Lanugage Navigation (VLN). Models trained on our generated data demonstrate strong zero-shot performance and show further improvement after finetuning. This demonstrates the viability of leveraging readily available web data as a path toward more capable scene understanding systems.

Efficient Reasoning with Balanced Thinking

✇cs.AI, q-bio.NC updates on arXiv.org
By: Yulin Li · Tengyao Tu · Li Ding · Junjie Wang · Huiling Zhen · Yixin Chen · Yong Li · Zhuotao Tian
3 April 2026 at 12:00
arXiv:2603.12372v3 Announce Type: replace Abstract: Large Reasoning Models (LRMs) have shown remarkable reasoning capabilities, yet they often suffer from overthinking, expending redundant computational steps on simple problems, or underthinking, failing to explore sufficient reasoning paths despite inherent capabilities. These issues lead to inefficiencies and potential inaccuracies, limiting practical deployment in resource-constrained settings. Existing methods to mitigate overthinking, such as suppressing reflective keywords or adjusting reasoning length, may inadvertently induce underthinking, compromising accuracy. Therefore, we propose ReBalance, a training-free framework that achieves efficient reasoning with balanced thinking. ReBalance leverages confidence as a continuous indicator of reasoning dynamics, identifying overthinking through high confidence variance and underthinking via consistent overconfidence. By aggregating hidden states from a small-scale dataset into reasoning mode prototypes, we compute a steering vector to guide LRMs' reasoning trajectories. A dynamic control function modulates this vector's strength and direction based on real-time confidence, pruning redundancy during overthinking, and promoting exploration during underthinking. Extensive experiments conducted on four models ranging from 0.5B to 32B, and across nine benchmarks in math reasoning, general question answering, and coding tasks demonstrate that ReBalance effectively reduces output redundancy while improving accuracy, offering a general, training-free, and plug-and-play strategy for efficient and robust LRM deployment. Project page and code are available at https://rebalance-ai.github.io .
Received — 17 March 2026 ⏭

Efficient Reasoning with Balanced Thinking

✇cs.AI, q-bio.NC updates on arXiv.org
By: Yulin Li · Tengyao Tu · Li Ding · Junjie Wang · Huiling Zhen · Yixin Chen · Yong Li · Zhuotao Tian
16 March 2026 at 12:00
arXiv:2603.12372v1 Announce Type: new Abstract: Large Reasoning Models (LRMs) have shown remarkable reasoning capabilities, yet they often suffer from overthinking, expending redundant computational steps on simple problems, or underthinking, failing to explore sufficient reasoning paths despite inherent capabilities. These issues lead to inefficiencies and potential inaccuracies, limiting practical deployment in resource-constrained settings. Existing methods to mitigate overthinking, such as suppressing reflective keywords or adjusting reasoning length, may inadvertently induce underthinking, compromising accuracy. Therefore, we propose ReBalance, a training-free framework that achieves efficient reasoning with balanced thinking. ReBalance leverages confidence as a continuous indicator of reasoning dynamics, identifying overthinking through high confidence variance and underthinking via consistent overconfidence. By aggregating hidden states from a small-scale dataset into reasoning mode prototypes, we compute a steering vector to guide LRMs' reasoning trajectories. A dynamic control function modulates this vector's strength and direction based on real-time confidence, pruning redundancy during overthinking, and promoting exploration during underthinking. Extensive experiments conducted on four models ranging from 0.5B to 32B, and across nine benchmarks in math reasoning, general question answering, and coding tasks demonstrate that ReBalance effectively reduces output redundancy while improving accuracy, offering a general, training-free, and plug-and-play strategy for efficient and robust LRM deployment. Code is available at https://github.com/yu-lin-li/ReBalance .
Received — 5 March 2026 ⏭

RANGER: Sparsely-Gated Mixture-of-Experts with Adaptive Retrieval Re-ranking for Pathology Report Generation

✇cs.AI, q-bio.NC updates on arXiv.org
By: Yixin Chen · Ziyu Su · Hikmat Khan · Muhammad Khalid Khan Niazi
5 March 2026 at 13:00
arXiv:2603.04348v1 Announce Type: cross Abstract: Pathology report generation remains a relatively under-explored downstream task, primarily due to the gigapixel scale and complex morphological heterogeneity of Whole Slide Images (WSIs). Existing pathology report generation frameworks typically employ transformer architectures, relying on a homogeneous decoder architecture and static knowledge retrieval integration. Such architectures limit generative specialization and may introduce noisy external guidance during the report generation process. To address these limitations, we propose RANGER, a sparsely-gated Mixture-of-Experts (MoE) framework with adaptive retrieval re-ranking for pathology report generation. Specifically, we integrate a sparsely gated MoE into the decoder, along with noisy top-$k$ routing and load-balancing regularization, to enable dynamic expert specialization across various diagnostic patterns. Additionally, we introduce an adaptive retrieval re-ranking module that selectively refines retrieved memory from a knowledge base before integration, reducing noise and improving semantic alignment based on visual feature representations. We perform extensive experiments on the PathText-BRCA dataset and demonstrate consistent improvements over existing approaches across standard natural language generation metrics. Our full RANGER model achieves optimal performance on PathText dataset, reaching BLEU-1 to BLEU-4 scores of 0.4598, 0.3044, 0.2036, and 0.1435, respectively, with METEOR of 0.1883, and ROUGE-L of 0.3038, validating the effectiveness of dynamic expert routing and adaptive knowledge refinement for semantically grounded pathology report generation.
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