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Received — 18 September 2026 ⏭

Integrated multi-omic and functional profiling reveals a ZDHHC16-associated palmitoylation-proteostasis state in hepatocellular carcinoma

✇(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)
By: Lihua Zhang · Xiaolei Zhang · Caiqi Liu · Xiaofei Xin · Xinchi Luan · Jialin Song · Wensheng Qiu
15 September 2026 at 18:00

Discov Oncol. 2026 Aug 1;17(1):1333. doi: 10.1007/s12672-026-05700-y.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) remains biologically heterogeneous, and molecular states linking tumor-cell intrinsic programs with post-translational regulation, immune contexture and drug-specific vulnerability remain incompletely defined. ZDHHC16 is a DHHC-family palmitoyl acyltransferase, but its clinical relevance and biological context in HCC remain unclear.

METHODS: Public transcriptomic, clinical, single-cell, proteomic, palmitoylome, immune-related and pharmacogenomic datasets were integrated to characterize ZDHHC16 in HCC. ZDHHC16 expression, exploratory survival separation, cellular localization, pathway activity, palmitoylation-associated candidates, immune microenvironment features and predicted drug response were evaluated. siRNA-mediated knockdown, MTT assays and colony formation assays were performed in HepG2 and Huh7 cells.

RESULTS: ZDHHC16 was upregulated in HCC. In exploratory Kaplan-Meier analyses restricted to primary tumors and using endpoint-specific data-derived cutoffs, the curves showed expression-group separation for overall survival, disease-free interval and progression-free interval (unadjusted log-rank P = 0.019, 0.019 and 0.011, respectively). These analyses were not adjusted for clinical covariates and do not establish independent prognostic value. Single-cell analysis localized ZDHHC16 mainly to malignant epithelial-related compartments. ZDHHC16 knockdown reduced MTT-based cell viability and clonogenic growth in HepG2 and Huh7 cells. ZDHHC16-high tumors were enriched for cell-cycle progression, DNA replication, DNA repair, RNA processing, ubiquitin-mediated proteolysis and proteasome-related programs. After deduplication at the gene-symbol level, palmitoylome-guided integration nominated 28 transcriptionally correlated palmitoylation-associated candidates, including EZH2, PI4K2A and ZDHHC6; the screen did not establish direct ZDHHC16 substrates. ZDHHC16-high tumors also showed immune-remodeled features and drug-specific predicted IC50 patterns.

CONCLUSIONS: Integrated data support ZDHHC16 as a marker of a malignant epithelial, growth-associated HCC state accompanied by palmitoylation- and proteostasis-related programs, altered immune contexture and drug-specific predicted IC50 patterns. Direct ZDHHC16-dependent palmitoylation, independent prognostic value and therapeutic utility require biochemical and prospective clinical validation.

PMID:42742876 | PMC:PMC13578202 | DOI:10.1007/s12672-026-05700-y

Received — 27 May 2026 ⏭

Spatial multi-omics technologies in gastric cancer: applications and advances

✇Omics in Gastric
By: Qianqian Liu · Haowen Liu · Jing Lv · Jiashuo Li · Guangtan Du · Wensheng Qiu · Shasha Wang
30 April 2026 at 18:00

Front Immunol. 2026 Apr 14;17:1767512. doi: 10.3389/fimmu.2026.1767512. eCollection 2026.

ABSTRACT

Gastric cancer (GC) is plagued by profound intratumoral heterogeneity and a complex tumor microenvironment (TME), which are the core obstacles to precise diagnosis and treatment. Conventional bulk multi-omics technologies average molecular signals across tissues, thus masking cellular heterogeneity; single-cell multi-omics resolves cellular diversity but dissociates cells from their native spatial context, leading to the loss of critical information on intercellular crosstalk and molecular spatial distribution. These limitations result in an incomplete understanding of GC pathogenesis and TME regulatory networks. Spatial multi-omics technologies, integrating genomics, transcriptomics, proteomics, and metabolomics with high-resolution spatial localization, address these key scientific problems by preserving the native tissue architecture and elucidating the spatiotemporal dynamics of molecular and cellular events in GC. This review systematically synthesizes the latest advances in the application of four major spatial multi-omics modalities in GC research over the past 15 years, with a critical evaluation of the technical performance, methodological shortcomings, and clinical translation potential of existing studies. Unlike previous reviews that only summarize research findings, this work uniquely integrates technical principles, mechanistic discoveries, and clinical translation of spatial multi-omics in GC, deeply analyzes the practical barriers to clinical application, and systematically elaborates the integration of spatial multi-omics with artificial intelligence (AI). We also identify unresolved challenges in the field and propose future development directions, providing a comprehensive and in-depth reference for the advancement of GC precision medicine based on spatial multi-omics.

PMID:42058209 | PMC:PMC13120937 | DOI:10.3389/fimmu.2026.1767512

Received — 17 February 2026 ⏭

LLM-Confidence Reranker: A Training-Free Approach for Enhancing Retrieval-Augmented Generation Systems

✇cs.AI, q-bio.NC updates on arXiv.org
By: Zhipeng Song · Xiangyu Kong · Xinrui Bao · Yizhi Zhou · Jiulong Jiao · Sitong Liu · Yuhang Zhou · Heng Qi
17 February 2026 at 13:00
arXiv:2602.13571v1 Announce Type: cross Abstract: Large language models (LLMs) have revolutionized natural language processing, yet hallucinations in knowledge-intensive tasks remain a critical challenge. Retrieval-augmented generation (RAG) addresses this by integrating external knowledge, but its efficacy depends on accurate document retrieval and ranking. Although existing rerankers demonstrate effectiveness, they frequently necessitate specialized training, impose substantial computational expenses, and fail to fully exploit the semantic capabilities of LLMs, particularly their inherent confidence signals. We propose the LLM-Confidence Reranker (LCR), a training-free, plug-and-play algorithm that enhances reranking in RAG systems by leveraging black-box LLM confidence derived from Maximum Semantic Cluster Proportion (MSCP). LCR employs a two-stage process: confidence assessment via multinomial sampling and clustering, followed by binning and multi-level sorting based on query and document confidence thresholds. This approach prioritizes relevant documents while preserving original rankings for high-confidence queries, ensuring robustness. Evaluated on BEIR and TREC benchmarks with BM25 and Contriever retrievers, LCR--using only 7--9B-parameter pre-trained LLMs--consistently improves NDCG@5 by up to 20.6% across pre-trained LLM and fine-tuned Transformer rerankers, without degradation. Ablation studies validate the hypothesis that LLM confidence positively correlates with document relevance, elucidating LCR's mechanism. LCR offers computational efficiency, parallelism for scalability, and broad compatibility, mitigating hallucinations in applications like medical diagnosis.

An Agentic System for Rare Disease Diagnosis with Traceable Reasoning

✇cs.AI, q-bio.NC updates on arXiv.org
By: Weike Zhao · Chaoyi Wu · Yanjie Fan · Xiaoman Zhang · Pengcheng Qiu · Yuze Sun · Xiao Zhou · Yanfeng Wang · Xin Sun · Ya Zhang · Yongguo Yu · Kun Sun · Weidi Xie
17 February 2026 at 13:00
arXiv:2506.20430v3 Announce Type: replace-cross Abstract: Rare diseases affect over 300 million individuals worldwide, yet timely and accurate diagnosis remains an urgent challenge. Patients often endure a prolonged diagnostic odyssey exceeding five years, marked by repeated referrals, misdiagnoses, and unnecessary interventions, leading to delayed treatment and substantial emotional and economic burdens. Here we present DeepRare, a multi-agent system for rare disease differential diagnosis decision support powered by large language models, integrating over 40 specialized tools and up-to-date knowledge sources. DeepRare processes heterogeneous clinical inputs, including free-text descriptions, structured Human Phenotype Ontology terms, and genetic testing results, to generate ranked diagnostic hypotheses with transparent reasoning linked to verifiable medical evidence. Evaluated across nine datasets from literature, case reports and clinical centres across Asia, North America and Europe spanning 14 medical specialties, DeepRare demonstrates exceptional performance on 3,134 diseases. In human-phenotype-ontology-based tasks, it achieves an average Recall@1 of 57.18%, outperforming the next-best method by 23.79%; in multi-modal tests, it reaches 69.1% compared with Exomiser's 55.9% on 168 cases. Expert review achieved 95.4% agreement on its reasoning chains, confirming their validity and traceability. Our work not only advances rare disease diagnosis but also demonstrates how the latest powerful large-language-model-driven agentic systems can reshape current clinical workflows.
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