❌

Normal view

A nonlinear multi-omics data integration and classification model based on pathway self-attention and graph convolutional networks

Yi Chuan. 2026 Sep;48(9):931-945. doi: 10.16288/j.yczz.25-275.

ABSTRACT

The abundance of omics data has significantly advanced the development of multi-omics data integration techniques. Non-linear embedding approaches for data integration have gradually become the mainstream in multi-omics research, as these approaches can substantially improve cancer analysis by enhancing the quality of the embeddings. However, current multi-omics data integration methods are typically confined to omics measurements, neglecting domain-specific prior knowledge encompassing biological pathways. In this study, we proposed a multi-omics integrated classification model, PathTransGCN, based on pathway self-attention and graph convolutional networks (GCN). The model integrated biological pathway information into multi-omics data analysis with the aim of enhancing the accuracy of cancer classification. Multi-omics data for breast cancer (BRCA), non-small cell lung cancer (NSCLC), and low-grade glioma (LGG) were obtained from The Cancer Genome Atlas (TCGA) and UCSC Xena databases. These data included gene mutations, DNA methylation, copy number variations, and gene expression, and were used to assess the model's generalizability across different cancers. First, PathTransGCN employed a pathway self-attention module to learn latent representations of samples across different pathways, thereby obtaining multi-omics integration vectors. Concurrently, a patient similarity network (PSN) was constructed using the similarity network fusion (SNF) approach. Second, the integrated vectors and the PSN were jointly fed into a GCN for end-to-end training, enabling precise classification of cancer subtypes. Through multi-omics data analysis of the BRCA dataset, PathTransGCN outperformed several popular algorithms (such as MoGCN and DeePathNet) in the five-class classification of cancer subtypes, achieving an accuracy rate of 87.6% and an F1 score of 86.4%. Moreover, the model demonstrated robust generalization capabilities across both NSCLC and LGG datasets, while effectively identifying key disease-associated biomarkers at the pathway level. Experimental results demonstrate that PathTransGCN exhibits outstanding performance in integrating omics data and delivering interpretable classification outcomes, presenting significant potential for clinical applications.

PMID:42751828 | DOI:10.16288/j.yczz.25-275

Artificial Intelligence-Driven Multiomics and Clinical Investigation Identify Macrophage Migration Inhibitory Factor as a Pan-Cancer Biomarker

Phenomics. 2026 May 20;6(3):213-229. doi: 10.1007/s43657-026-00322-4. eCollection 2026 Jun.

ABSTRACT

Early cancer detection remains challenging due to the lack of reliable pan-cancer screening methods, particularly blood-based biomarkers. Using a novel three-tiered validation framework combining artificial intelligence (AI)-powered literature mining of 180,000 PubMed articles (1950-2024), multiomics integration across major databases, and extensive clinical validation, we identified macrophage migration inhibitory factor (MIF) as a promising blood-based biomarker for pan-cancer detection. Multiomics analysis revealed consistent MIF upregulation across 21 cancer types at the transcriptional level and across 12 cancer types at the protein level. Clinical validation in independent cohorts (n = 4,269) showed that serum MIF protein levels discriminated effectively between cancer patients and healthy controls (median AUC = 0.994) and between cancer and benign conditions (median AUC = 0.881). Notably, comparative analyses showed that MIF demonstrated superior or comparable performance to established cancer-specific markers, including AFP for hepatocellular carcinoma (MIF AUC = 0.885 vs. AFP AUC: 0.744-0.887) and CA125 for ovarian cancer (MIF AUC = 0.831 vs. CA125 AUC: 0.58-0.71). Meta-analysis of 28 cohorts (n = 5,347) confirmed the diagnostic efficacy of MIF (pooled AUC: 0.782). This cost-effective, blood-based ELISA approach establishes MIF as a valuable tool for broad applications in cancer screening.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s43657-026-00322-4.

PMID:42750739 | PMC:PMC13578188 | DOI:10.1007/s43657-026-00322-4

Levetiracetam therapeutically targets GABAergic synapses in diffuse midline glioma

Nature Medicine, Published online: 17 September 2026; doi:10.1038/s41591-026-04646-6

Results of this study show in experimental models and data from patient cohorts that the antiseizure medication levetiracetam is associated with longer survival and reduced tumor growth in diffuse midline glioma, but not hemispheric high-grade glioma, by selectively dampening GABAergic synaptic signaling, independently of its canonical SV2A-mediated primary antiseizure mechanism.

EBV reactivation priming of the peripheral immune system in multiple sclerosis relapse

Nature Medicine, Published online: 16 September 2026; doi:10.1038/s41591-026-04665-3

Increased expression of EBV reactivation genes in B cells and MS risk genes targeted by the EBV protein EBNA-2 precedes MS attacks, linking EBV reactivation and genetic risk to the development of MS relapses.

Factor IX Padua AAV gene therapy in adolescents with hemophilia B: a phase 1 trial

Nature Medicine, Published online: 16 September 2026; doi:10.1038/s41591-026-04636-8

In this single-arm phase 1 trial, an AAV gene therapy carrying the Padua variant of factor IX was well tolerated in 11 adolescents with hemophilia B and led to reductions in annualized bleeding rate.

ESAM reduces sensitivity to anti-HER2 therapy in HER2-positive breast cancer by activating the mTOR pathway

Cell Death Discovery, Published online: 16 September 2026; doi:10.1038/s41420-026-03349-8

ESAM reduces sensitivity to anti-HER2 therapy in HER2-positive breast cancer by activating the mTOR pathway

On-premise medical AI agents for reliable clinical decision-making

Nature Medicine, Published online: 15 September 2026; doi:10.1038/s41591-026-04609-x

An autonomous clinical AI agent enhances decision-making through on-premise deployment and reliability metrics, achieving high diagnostic accuracy and selective autonomy.

IFN-I induced-LAP3 promotes embryo resorption by inhibiting trophoblast mitophagy via targeting HSD17B10/PE pathway

Cell Death Discovery, Published online: 15 September 2026; doi:10.1038/s41420-026-03342-1

IFN-I induced-LAP3 promotes embryo resorption by inhibiting trophoblast mitophagy via targeting HSD17B10/PE pathway

Synthetic transcription factors designed by domain recombination enhance CAR T cell antitumor function

Recombining domains across an entire protein family, rather than relying on natural sequences shaped by evolution, generates synthetic “DESynR” transcription factors with enhanced function. DESynR AP-1 TFs reprogram CAR T cells into non-natural, therapeutically optimized states and outperform natural AP-1 factors in antitumor immunity.

Dietary arginine drives codon-dependent MHC class I translation and improves immunity in colon tumorigenesis and respiratory viral infection

Arginine availability regulates arginyl tRNA levels and codon-dependent translation of MHC class I, tuning antigen presentation and shaping anti-viral and anti-tumor immunity.

Advancing cancer detection and treatment using longitudinal routine clinical data

Liu et al. develop Oncoformer, a multimodal transformer that reads routine laboratory tests and chest X-rays already collected in everyday care. Across more than 3.6 million individuals, it detects cancer, infers tumor stage, and stratifies treatment response and recurrence risk, pointing toward risk-adapted cancer care built on data already in hand.

Digitally Adapting LGBTQ-Affirmative Cognitive Behavioral Therapy for Chinese Men Who Have Sex With Men Living With HIV: User-Centered Design Approach

Background: Chinese men who have sex with men living with HIV (MSMLWH) experience substantial psychological distress driven by minority stress and HIV-related challenges. However, culturally tailored digital mental health interventions that address HIV-specific maladaptive cognitive schemas and culturally specific psychosocial stressors remain scarce in China. Objective: This study aimed to systematically adapt an evidence-based cognitive behavioral therapy (CBT) intervention Effective Skills to Empower Effective Men (ESTEEM) into a WeChat (Tencent) Mini-Program–based intervention (iESTEEM) specifically for Chinese MSMLWH and to evaluate its preliminary feasibility and usability. Methods: We used a three-phase user-centered design approach guided by the Assessment, Decision, Adaptation, Production, Topical Experts, Integration, Training, and Testing (ADAPT-ITT) framework. The study proceeded in three phases: (1) a qualitative needs assessment using semistructured interviews with 20 MSMLWH (mean age 23.25, SD 3.08 years); (2) systematic intervention adaptation and platform development, including theater testing (n=5); and (3) a 2-week pilot study involving 10 MSMLWH and five counselors to evaluate feasibility, usability, and acceptability through focus groups and objective platform analytics. Results: Phase 1 identified 3 major themes of psychological distress: persistent health anxiety fueled by catastrophizing, intersectional stigma internalization, the disclosure dilemma, and intimacy barriers rooted in defectiveness and shame schemas. Participants also prioritized anonymity and bite-sized learning. Guided by these findings, iESTEEM was developed as a counselor-assisted, privacy-preserving WeChat Mini-Program incorporating HIV-specific scenarios, multimodal learning modules, and a back-end risk-alert system. During the 2-week pilot, participants logged into the platform 14.1 (SD 6.7) times per person and completed 134.3 (SD 103.1) minutes of learning activities; all participants accessed module 1, and 90% (9/10) accessed modules 2‐5. Anxiety scores decreased from 8.9 (SD 2.3) to 7.2 (SD 3.0), whereas depression scores remained stable. All participants expressed a willingness to continue using the program and to recommend it to peers. Participants and counselors endorsed its contextual relevance, privacy protections, and clinical utility. Conclusions: This study provides a theory- and evidence-informed model for culturally adapting digital mental health interventions for highly stigmatized populations. By integrating lesbian, gay, bisexual, transgender, and queer (LGBTQ)-affirmative CBT principles, HIV-specific adaptations, and a privacy-preserving, counselor-assisted WeChat Mini-Program, iESTEEM demonstrated promising preliminary feasibility, acceptability, and engagement among Chinese MSMLWH. These findings support the potential of culturally tailored digital interventions to expand access to psychological support for this stigmatized population in resource-constrained settings. Ongoing randomized controlled trials will further evaluate its efficacy, implementation outcomes, and mechanism of action. Trial Registration: Chinese Clinical Trial Registry ChiCTR2400080263; https://www.chictr.org.cn/showproj.html?proj=216926

Do Influence-Derived Data Perturbations Enable Machine Unlearning? A Controlled Study of Three Plausible Roles

arXiv:2609.12313v1 Announce Type: new Abstract: We evaluate Deep Perturbation Learning (DPL), which perturbs training images and labels along influence-derived directions, in three roles in which prior work has positioned it for machine unlearning: a direct deletion signal (the strongest claim), a utility-preserving regularizer, and a warm start for adversarial unlearning. Evidence for the weaker roles has been used to support the stronger one, so we test each role separately under a matched protocol with exact-seed retraining baselines. An audit of the public implementation identifies two correctness issues: image directions are computed on augmented, normalized tensors but applied to raw images, and the label perturbation falls below float32 resolution, leaving labels unchanged. After correcting the image-perturbation pipeline, DPL fails the direct-deletion criterion on CIFAR-10/ResNet-18 in all three paired seeds. Its utility effects are inconsistent in sign across seeds, and once direction-computation time is counted it underperforms simple warm-start baselines. A one-seed Tiny ImageNet check likewise does not favor DPL as a regularizer or warm start; preprocessing inconsistencies in the released code make the direct comparison there inconclusive. These results cover random instance deletion only and do not rule out influence-based methods in other deletion regimes. We release a role-matched evaluation protocol and an audit checklist for perturbation-based deletion claims.

BlueLM-GUI Technical Report: A Real-Device-Centric Flywheel for Self-Improving Mobile GUI Agents

arXiv:2609.12394v1 Announce Type: new Abstract: Mobile GUI agents are shifting from multi-module frameworks to native models trained end-to-end, yet industrial deployment faces three persistent gaps. Sandbox training produces a distribution mismatch with production environments; expensive real-device failures remain underutilized; and fixed benchmarks saturate, losing the power to guide iteration. We present BlueLM-GUI, a 35B-A3B mobile GUI agent built as a real-device-centric flywheel that closes these gaps through three principles. Every Sample Matters: a dual-track pipeline with Heterogeneous Triple-System Consensus evaluation and an Error Correction \& Derivation Module salvages every trajectory into usable supervision. Every Rollout Is Real: a three-stage recipe---continual pre-training, supervised fine-tuning, and agentic reinforcement learning on hundreds of real phones---grounds every rollout in real production environments, so the capability the model learns transfers directly to deployment. Every Query Evolves: a quota-driven benchmark methodology with three orthogonal axes enables precise attribution and allows the benchmark to be systematically upgraded as the model improves. BlueLM-GUI achieves 87.4 on MobileGUI-VBench, surpassing the best closed-source model by 5.1 points, and 84.9 on AndroidWorld, the best result among open-source models and competitive with closed-source models. These results demonstrate that grounding model training and iterative improvement in both real devices and the three Every principles yields strong, robust, and transferable mobile GUI capability.

SoK: Rethinking Jailbreaking in the Era of Agentic AI: Attacks, Defenses, and Practical Consideration

arXiv:2609.12413v1 Announce Type: new Abstract: Large language models (LLMs) are rapidly evolving from conversational assistants into agentic AI systems that reason, plan, invoke tools, maintain persistent memory, communicate with other agents, and execute multi-step tasks. At the same time, modern models exhibit substantially stronger native safety alignment than earlier generations on which many jailbreak attacks and defenses were originally studied. This shift raises a fundamental question: \textit{which established jailbreak-security findings remain valid in the era of modern LLMs and agentic AI?} We address this question through a Systematization of Knowledge (SoK) that reframes jailbreak security around the full agentic execution pipeline. We develop unified taxonomies of attacks and defenses spanning user interaction, planning and reasoning, memory, tool use, and inter-agent communication, and introduce a security--utility--efficiency evaluation framework that separates native harmful-prompt safety, adversarial jailbreak robustness, and agent-level security outcomes. We further conduct a controlled empirical study of representative attacks and defenses within a common agentic framework. Our results reveal three important gaps. First, strong native alignment does not imply robustness to adversarial jailbreaks. Second, defense effectiveness is highly model-, attack-, and component-dependent and can come at substantial cost in over-refusal, utility, and latency. Third, low final-response attack success can mask severe intermediate compromise: planning, memory, and tool interactions may remain unsafe even when the final response is successfully filtered. These findings motivate a shift from response-centric jailbreak defense toward cross-layer, execution-aware security that protects agent state, component transitions, and external actions while preserving practical utility and efficiency.

Do LLMs Trust the Accuser or the Accusation? Measuring Belief Shifts in Werewolf

arXiv:2609.12446v1 Announce Type: new Abstract: Social-deduction games such as Werewolf are increasingly used to evaluate LLM agents, but existing evaluations often rely on final game outcomes. We propose a belief-shift evaluation benchmark in Werewolf for analyzing communication skills through belief updating. Using LLM-played games, we annotate suspicion and accusation messages and measure how an observing village-side model's beliefs change after each message. We evaluate 40 open-weight LLM configurations on 1,224 annotated messages. Our results show that larger models better distinguish true wolves from villagers based on game history, but accusations still strongly influence their beliefs. Models become more suspicious of the accused target and less suspicious of the accuser, especially when the accuser is trusted, even if the accuser is wolf-aligned. Larger models better resist accusations from accusers they already distrust. Overall, our findings suggest that current open-weight LLMs up to 120B parameters still struggle to integrate accusation content with source trust in strategic communication. Our benchmark and code are available at https://rlg.iis.sinica.edu.tw/papers/werewolf-accusation-benchmark.

When Does AI Augment Work? A Workflow-Level Framework for Human-Agent Collaboration

arXiv:2609.12482v1 Announce Type: new Abstract: We aim to characterise the value of artificial intelligence in the workplace. Current studies largely measure this value in terms of the current automation capabilities and public adoption of AI. However, such metrics ignore the greater impacts of human--agent collaboration in transforming the nature of work. To account for this, we must expand the scope of our analysis beyond atomised tasks of today, and instead focus on how AI can augment entire workflows of the future. To ground this analysis, we establish a precise definition of AI augmentation comprising six conditions, spanning durable net value, meaningful human control, accountability and recovery, and long-term human development through learning, career pathways, and job purpose. We elaborate on these conditions and apply the framework in a case study of AI-mediated social surveys. We conclude by outlining how organisations, researchers, and government leaders can use this framework to make sense of the future of work.

SCQ: Stabilizing Conservative Q-Learning with Sigmoid-Bounded Entropy

arXiv:2609.12749v1 Announce Type: new Abstract: Offline-to-online reinforcement learning reduces interaction cost for real-world robot learning but suffers from persistent value estimation instability. Existing methods address this through pessimistic regularization, lower-bound calibration, and architectural normalization, but an overlooked source of instability lies in the entropy formulation: the standard log-entropy term can become negative, destabilizing policy updates. We introduce SCQ (Sigmoid-Bounded Conservative Q-Learning), which replaces this term with a sigmoid-bounded formulation that stays strictly positive. SCQ retains conservative Q regularization and return-based lower-bound calibration, stabilizing policy optimization without sacrificing exploration. We evaluate SCQ on D4RL (Minari) benchmarks under both single-demonstration and standard dataset settings, as well as on simulation and real-world visual tasks. SCQ matches or exceeds baseline performance while exhibiting more stable training dynamics across state-based and visual benchmarks, and transfers to four real-robot platforms including manipulation, wheeled, quadruped, and humanoid systems. A direct clipping intervention that removes negative log-probability contributions, together with gradient-matched positive-score controls, indicates that positivity rather than a particular score shape alone drives much of the improvement. Project website: https://scq-rl.github.io.

How Good Are Frontier Models at Physics? Expert Re-Grading Reveals Broken Evaluations and Near-Saturation of Leading Benchmarks

arXiv:2609.13009v1 Announce Type: new Abstract: Low reported scores on leading physics benchmarks, including those featured in the Artificial Analysis Intelligence Index (2026), suggest that frontier language models still struggle with advanced physics, a demanding test of their scientific reasoning and quantitative problem-solving abilities. Yet this impression does not always align with domain experts' experiences using these models in their work. We revisit these reported findings by evaluating frontier models on six widely used physics benchmarks and auditing them with experts, focusing on text-only problems with verifiable final answers. For each subfield of physics, faculty and graduate researchers with relevant expertise carefully review problem statements, reference solutions, and model responses to distinguish genuine model errors from grader errors, incorrect reference solutions, and ambiguous or underspecified questions. Most audited cases initially evaluated as incorrect reflect these benchmarking issues rather than errors in the models' physics reasoning. We then ask experts to address these benchmarking issues by correcting erroneous reference solutions and repairing or excluding flawed questions. We find that GPT-5.6-Sol's measured mean@4 rises from 47.3% to 78.7% on HLE-Physics and from 61.0% to 87.2% on CMT-Benchmark, while its corrected pass@4 reaches 94.4% on the 54 retained CritPt challenges. Corrected scores are computed on the retained evaluation subsets following expert review. Scores on the audited subsets of UGPhysics, PRISM-Physics, and PHYBench also rise substantially after correction. These findings suggest that current benchmarks substantially understate frontier models' ability to solve well-posed physics problems. Near-saturation on these closed-ended tasks highlights the need for more demanding, expert-validated evaluations.

UFO: Chain-of-Evaluation for Omni-Condition Alignment in Multi-Modal Image Generation

arXiv:2609.12397v1 Announce Type: cross Abstract: Multi-modal image generation, particularly subject-driven customization, has garnered growing attention in recent years. Despite the rapid advancement of generative models, their evaluation remains largely lagging. Existing methods, whether embedding-based or Multi-modal Large Language Model (MLLM)-based, evaluate alignment with each modal condition in isolation, which contradicts the simultaneous condition alignment objective of multi-modal image generation, leading to poor consistency with human judgments. To address this challenge, we propose UFO, the first unified framework for omni-condition alignment simultaneous evaluation. Specifically, UFO introduces a novel Atomized Chain-of-Evaluation paradigm, \emph{i.e.}, it first decomposes omni-condition alignment into a sequential chain of fine-grained, disentangled Atomic Evaluation Units (AEUs), categorizes them into distinct modality-relevance classes, and then employs general or dedicated functional calls for accurate verification of different AEU types. Experimental results demonstrate that UFO achieves the highest correlation with human evaluation preferences, delivering an average improvement of 15.25\%. Furthermore, we present UFO-Bench, a dedicated benchmark designed to holistically evaluate the performance of existing customization models under the diverse mutual interactions of textual and visual conditions.
❌