Research articles

NIPBL perturbation activates long terminal repeat (LTR)-derived alternative promoters due to reorganization of chromatin’s hierarchical structure, leading to LTR co-option and oncogene activation in melanoma cell lines.

Single-cell RNA sequencing, whole-exome sequencing and spatial transcriptome sequencing of gallbladder adenocarcinomas from 75 patients stratifies the disease into groups with distinct clinical outcomes.

Single-cell and spatial transcriptomics analysis of stricturing Crohn’s disease highlights cellular heterogeneity in fibrotic tissue and identifies neighborhoods of fibroblasts and immune cells contributing to this severe disease complication.

Single-cell analyses of liver biopsies from patients with metabolic dysfunction-associated steatohepatitis and healthy controls identify cell-state-interacting expression quantitative trait loci with significant enrichment for disease heritability.

Here the authors show that chromosomal instability signatures can predict resistance to anthracycline-, taxane- and platinum-based chemotherapeutics in breast, ovarian and prostate cancer and sarcoma. Validation is performed through emulation of phase 2 and 3 clinical trials using real-world data.

This study integrates polygenic risk scores with four emulated clinical trials using FinnGen data and shows the feasibility of this approach while highlighting potential pitfalls.

Polygenic risk scores for Alzheimer’s disease derived from individuals of European ancestry can show improved performance in multiancestry settings after incorporating genome-wide association summary statistics from diverse populations.

A genome-wide screen using human gut epithelial organoids combined with transposon-directed insertion sequencing identifies over 100 Shigella flexneri genes required for epithelial colonization.

This study introduces pgBoost, a gradient boosting framework that predicts regulatory single-nucleotide polymorphism–gene links by combining existing linking scores from single-cell multiomics datasets and genomic distance.

This study maps regulatory variation in blood using whole-genome and transcriptome data from 614 South Africans, providing a resource to aid the interpretation of genome-wide association studies in African populations.

Comparison of genome-wide association studies of HTT CAG repeat expansion in blood to expansion-driven clinical traits in Huntington’s disease identifies shared and distinct modifiers implicating DNA mismatch repair with tissue and cell-type specificity.

The study reports the cloning of paired NLR genes CNL and NL from wild emmer wheat and demonstrates their coordinated function in conferring Yr84-mediated wheat stripe rust resistance.

The powdery mildew resistance of the MLIW170/PM26 locus, which originated from wild emmer wheat, is determined by a genetically linked atypical NLR gene pair, TdCNL1 and TdCNL5, with TdCNL1 encoding an atypical nucleotide-binding leucine-rich repeat protein integrating a potassium-dependent sodium-calcium exchanger ___domain.

Two genetically linked TdNLR genes from wild emmer wheat are both required for YrTD121-mediated stripe rust resistance. The TdNLR1 and TdNLR2 pair lacks an integrated ___domain, representing an uncommon architecture for paired NLRs in plants.

Multiomic analysis of blast-phase myeloproliferative neoplasms identifies a chromosome 21 amplicon harboring DYRK1A as a clonal and therapeutically targetable event in around a quarter of cases.

High-resolution, spatial transcriptomic analysis of colorectal cancers using matched sequencing- and imaging-based methods characterizes immune cells and their interactions with the tumor microenvironment.

KDM4C regulates cathepsin L-mediated histone H3 N-terminal tail clipping through grainyhead-like 2 (GRHL2) methylation in breast cancer. This link between the cellular redox state and chromatin remodeling might represent a therapeutic target in KDM4C-amplified tumors.

A pan-cancer analysis of genomic data from matched primary and metastatic tumors from 3,732 patients shows that increased genomic complexity and alterations that facilitate immune evasion are associated with disease progression.

Phylogenetic analyses in patients with cancer and xenograft models highlight heterogeneity within individual CTC clusters, providing insights into clonal dynamics during metastasis.

Genomic analyses focused on regions that form R-loops identify rare mutations in RNU2-2 and RNU5B-1 in individuals with neurodevelopmental disorders.