Communications Biology

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with poor prognosis and limited therapies. To elucidate its post-transcriptional regulation, ceRNA networks were reconstructed from TCGA-ACC and GTEx 2025 data. Tumor networks exhibited compact topology and tumor-specific hub miRNAs (miR-466, miR-940, miR-507), which were downregulated, inversely correlated with oncogenic transcripts, and associated with adverse survival. Candidate targets were identified through dual validation ...

Background and ObjectivesRecent large-scale studies have consistently linked healthy dietary patterns to improved cardiometabolic health; however, the underlying biological pathways remain largely unclear, especially in non-European populations. In this study, we leverage data from four population-based cohorts (UK Biobank, NEO study, GNHS, and 10K) to investigate both common and cohort-specific biological pathways linking healthy dietary patterns to cardiometabolic disease through multi-omics p...

Primary open-angle glaucoma (POAG) disproportionately affects individuals of African ancestry, yet rare coding variation in this population remains understudied. To address this gap, we performed a multi-cohort exome-wide meta-analysis across POAAGG, PMBB, All of Us, and UK Biobank, including 4,815 POAG cases and 22,922 controls of genetically inferred African ancestry. Although no gene reached exome-wide significance, we identified several suggestive gene-level associations driven by rare varia...

ImportanceGenome-wide association studies have identified hundreds of common single nucleotide polymorphisms (SNPs) and small insertions/deletions (indels) associated with primary open-angle glaucoma (POAG) risk, though these variants have modest effect sizes and individually may have minor contributions to disease development. As whole-genome sequencing data is becoming more readily available, structural variants and other complex genomic features can be interrogated for contribution to disease...

PurposeTo identify genetic variants associated with glucocorticoid (GC)-induced intraocular pressure (IOP) change using genome-wide association study (GWAS) and whole exome sequencing (WES) analyses. Methods530 participants from the Fluocinolone Acetonide in Diabetic Macular Edema (FAME) trials were analyzed, with replication performed in an independent cohort of 588 participants from the Mass Eye and Ear/Retina Health Center (MEE/RHC). All participants were exposed to GC, primarily via intravi...

An increased emphasis on disease prevention is essential to improve population health and reduce healthcare resource needs. Key requirements for effective population scale prevention programmes are an optimal balance between simplicity of screening and accuracy of risk prediction at individual level. We developed models of varying complexity to predict the incident risk of 24 diseases in the UK Biobank population, testing combinations of modalities including established clinical variable-based r...

The Endoplasmic Reticulum AminoPeptidase 2 (ERAP2) gene encodes an aminopeptidase involved in antigenic peptide processing for the MHC-I pathway. Genetic variants in the ERAP2 gene are associated with autoimmune conditions and infectious diseases. The linkage between genetic variants in the ERAP2 gene has given rise to the prevailing assumption that a single ERAP2 allotype with invariant amino acid sequence accounts for all immunological functions of ERAP2. Here, we show by analyzing exon-sequen...

BackgroundShort stature (SS) is associated with adverse clinical, psychosocial, and economic outcomes, and early identification of at-risk individuals may enable timely evaluation and intervention. Polygenic risk scores (PRS) for height offer a promising strategy for SS risk stratification. However, substantial ancestry-related differences in PRS distributions and predictive performance limit equitable clinical translation. Improving cross-ancestry generalizability is therefore essential for rel...

The integration of causal effect estimates from multiple Mendelian Randomization studies has become increasingly popular. However, the presence of overlapping databases compromises traditional meta-analysis, leading to inflated variance and reduced statistical power. Here, we propose JointMR, a joint likelihood-based approach designed to integrate multiple GWAS summary databases while explicitly accounting for the covariance matrix of the Wald ratio estimates. Specifically, to accommodate potent...

Polygenic scores (PGS) show promise for disease risk stratification but suffer from limited portability across populations. American Indians face a disproportionate burden of cardiovascular disease yet remain significantly underrepresented in genomic research, limiting equitable access to precision medicine. Here, we evaluate whether integrating specific lifestyle and clinical context variables with PGS enhances risk prediction for cardiometabolic traits in 424,622 European from UK Biobank (UKB)...

Genome-wide association studies (GWAS) are conventionally conducted in cohorts spanning a wide age-range. These studies typically assume that genetic associations are constant across different ages. Some traits, however, may have age-varying genetic associations. This has implications for the interpretation of genetic effects derived in downstream applications, such as Mendelian randomization (MR) analyses. In this study we conducted a series of age-stratified GWAS on individuals aged 40-69 year...

BackgroundGenomic assays such as Oncotype DX, MammaPrint, and Prosigna have transformed risk stratification and treatment selection in early-stage, estrogen receptor-positive (ER+), HER2-negative breast cancers by enabling more precise prognostication and chemotherapy de-escalation in selected patients. However, their clinical utility is limited in lymph nodes positive disease. A major unmet need is the development of compact, mechanistically grounded biomarkers that extend risk and treatment-re...

PURPOSEBEST1-associated inherited retinal disease constitutes one of the largest inherited retinal disease patient populations across the world. Innovative therapies are currently in development to address this significant unmet need. To better understand the scale of unmet need, and the distribution of phenotypes and genotypes, we conducted a meta-analysis of BEST1 patients reported in the literature to provide up-to-date patient number estimates. METHODSWe utilized the GeneScape(R) IRD Patien...

BackgroundPancreatic ductal adenocarcinoma is one of the most aggressive and lethal malignancies of the gastrointestinal tract. The poor prognosis is largely attributed to late-stage diagnosis, pronounced tumor heterogeneity, and limited therapeutic efficacy. These challenges underscore the urgent need for the identification of robust molecular biomarkers and novel therapeutic targets. MethodsGene expression data from a total of 146 pancreatic tissue samples, comprising 72 normal and 74 tumor s...

Genome-wide association studies of physical activity traits have mapped numerous loci, yet the molecular mechanisms through which exercise influences human biology remain poorly defined. Mechanistic progress has been limited by heritability-dominated signals, siloed single-omic analyses, and the lack of integrative models that connect genetic associations to causal, system-level pathways. We introduce the first deep learning, multi-omic framework for exercise genomics, unifying causal inference,...

ObjectiveProstate cancer (PCa) constitutes a considerable public health concern worldwide, primarily attributable to its elevated mortality rates. Changes in exosome are shown to significantly influence tumor development. This study aimed to investigate the prognostic value of exosome-related genes (ERGs) in PCa. MethodsPCa single-cell RNA sequencing (scRNA-seq) and transcriptome datasets were obtained from public databases, with ERGs extracted from existing literature. Candidate genes were ide...

Clear cell renal cell carcinoma (ccRCC) is the leading cause of kidney cancer-related death, but how the tumor microenvironment shapes patient survival is not completely understood. Here, we describe the characterization of ccRCC tumor ecosystems from 498 patients using imaging mass cytometry with a focus on tumor, myeloid, and T cell landscapes. Data from more than 3 million single cells is analyzed using machine-learning to identify key ecosystem features that outperform basic clinical data fo...

Cancer heterogeneity is traditionally attributed to multiple parallel signaling pathways. This belief is challenged here by proposing the ER/PR axis as the dominant pathway underlying the full spectrum of breast cancer. Absolutely quantitated ER, PR, Her2 and Ki67 protein levels were accumulated over 8 years from 1652 specimens collected non-selectively and measured with Quantitative Dot Blot (QDB) method over time. Cox analysis showed ER and Ki67 as independent adverse prognostic factors while ...

The use of semaglutide (SE), a glucagon-like peptide-1 receptor agonist (GLP-1RA) with glucose-lowering and weight-loss effects, has risen rapidly, particularly among women of reproductive age. While preclinical studies suggest benefits for ovarian function via the hypothalamic-pituitary-ovarian axis, its impact on the endometrial-embryo interface remains unclear. Here, we show that GLP-1R is dynamically expressed in fertile human endometrium, restricted to epithelial cells and markedly upregula...

Pathology classification of cancer tumor subtypes and benign tumors can be difficult due to cellular heterogeneity and similar morphological features. Renal Cell Cancer (RCC) poses a major challenge for uropathologists as advanced RCC is often incidentally diagnosed with complex histological characteristics. We hypothesised that molecular profiling of RCC and benign tumor specimen by mass spectrometry with machine learning methods enable accurate tumor classification and identification of candid...