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Genome-wide analyses identify 30 independent loci associated with obsessive–compulsive disorder, highlighting genetic overlap with other psychiatric disorders and implicating putative effector genes and cell types contributing to its etiology.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare cancer. Here, the authors develop a NLPHL specific model to identify 34 distinct cell states across 14 cell types that co-occur within 3 lymphocyte predominant ecotypes (LPEs) for 171 cases.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

A new study from the eMERGE consortium provides insights on the development of a pipeline for the generation and reporting of polygenic risk scores for ten diseases to diverse populations in a clinical setting.

Abnormal, misfolded tau proteins are found in cognitively normal individuals and Tauopathies, suggesting not all tau species are pathogenic. Here, the authors show tau seeding and post-translational modification profiles were associated with Aβ neuritic plaque density and differentiated two tauopathies.

Golub and colleagues tested thousands of drugs not originally developed for oncology across 578 human cancer cell lines, revealing growth-inhibitory effects and providing a resource to identify drugs with the potential to be repurposed for cancer.

The capacity of brain networks to retain information during aging is crucial but not yet known. This study shows that the brain’s memory capacity, modelled with reservoir computing, offers new insights into aging, brain function and cognitive decline.

Surgery poses significant risks for patients, with attempts to mitigate these risks using multimodal perioperative care pathways. Here, the authors show that preoperative hypercaloric carbohydrate drinks not only alleviate surgical stress but also demonstrates the replicability of this protection using FGF21 treatment alone.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

A study comparing the pattern of single-nucleotide variation between unique and duplicated regions of the human genome shows that mutation rate and interlocus gene conversion are elevated in duplicated regions.

Frogs are an ancient and ecologically diverse group of amphibians that include important model systems. This paper reports genome sequences of multiple frog species, revealing remarkable stability of frog chromosomes and centromeres, along with highly recombinogenic extended subtelomeres.

Market integration may loosen the dense kinship networks maintaining high fertility among agriculturalists, but data are lacking. Here, Colleran shows that in 22 rural Polish communities, women’s ego networks are less kin-oriented, but not less dense, as market integration increases, potentially enabling low fertility values to spread.

EchoNext, a deep learning model for electrocardiograms trained and validated in diverse health systems, successfully detects many forms of structural heart disease, supporting the potential of artificial intelligence to expand access to heart disease screening at scale.

We developed PRINT, a computational method that identifies footprints of DNA–protein interactions from bulk and single-cell chromatin accessibility data across multiple scales of protein size.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

Genome-wide comparative analysis of DNA binding for 200 transcription factors in two maize inbred lines reveals prevalent genotype-specific variation that is associated with gene expression differences and agronomic traits.

An initial draft of the human pangenome is presented and made publicly available by the Human Pangenome Reference Consortium; the draft contains 94 de novo haplotype assemblies from 47 ancestrally diverse individuals.

Base editing of the pathogenic trinucleotide repeat expansions underlying Huntington’s disease and Friedreich’s ataxia introduces repeat interruptions that reduce somatic expansion in patient cells and mice.

Serological tests are important diagnostic and disease surveillance tools for addressing the COVID-19 pandemic. Here, the authors present a tri-part Nanoluciferase based assay to detect antibodies against SARS-CoV-2.

Human papillomavirus (HPV) is a known cause of cervical cancer. Here, the authors perform a multi-omic analysis using published cervical squamous cell carcinoma cohorts from the USA, Europe, and SubSaharan Africa and identify two cervical squamous cell carcinoma subtypes that display prognostic differences.

Bock and colleagues perform integrative analysis of JAK-STAT mutant mice and find JAK-STAT signaling regulates CD8⁺ T cell and macrophage homeostasis by contributing to a poised epigenetic and transcription-regulatory state, preparing cells to rapidly respond to stimuli.

By developing a method for single-embryo multi-omics in Drosophila, the authors provide a high-resolution view into the transcriptional and metabolic underpinnings of early embryonic development.

Cross-sectional and longitudinal PET imaging of amyloid beta and tau in the human brain is combined with gene expression profiles to define the interactions between Alzheimer’s disease-related pathology propagation and brain-region-specific vulnerability.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

Phenotypic screening in cancer cell lines combined with chemogenomics analysis reveals a correlation between DNMDP sensitivity and increased PDE3A expression. DNMDP binding to PDE3A induces a switch resulting in interactions with SLFN12 and SIRT7.

A nanoscale polymer layer formed by mucins at the surface of tumour cells protects them against immune cell attack. This shield can be circumvented through immune cell engineering, using chimeric antigen receptors to stimulate natural killer and T cells or by tethering glycocalyx-editing enzymes to immune cells.

Liebers and colleagues present a prospective non-interventional trial in 80 individuals with hematologic cancer investigating the potential of ex vivo drug response profiling and show it to be clinically feasible.

A database of microbial signatures is used for systematic comparison of differential abundance patterns.

Engineered live bacteria could represent a new class of therapeutic treatment for human disease. Here, the authors use a human gut-on-a-chip microfluidics system to characterize an engineered live bacterial therapeutic, designed for the treatment of phenylketonuria, and to construct mathematical models that predict therapeutic strain function in non-human primates.

Genome-wide association analyses identify 123 susceptibility loci for migraine and implicate neurovascular mechanisms in its pathophysiology. Subtype analyses highlight risk loci specific for migraine with or without aura in addition to shared risk variants.

SPI1 fusion genes in T-cell acute lymphoblastic leukemia (T-ALL) are commonly found with co-occurring NRAS mutations. Here, the authors show that the combination of these oncogenes is necessary to drive T-ALL in a murine model and that the oncogenic activity of the SPI1 fusion is dependent on β-catenin.

Aneuploid cancer cell lines show increased dependence on the spindle assembly complex (SAC); initially they are resistant to SAC perturbations, but over time they accumulate chromosomal aberrations that impair their fitness.

Estimated glomerular filtration rate (eGFR) is a measure of kidney function and used to characterize chronic kidney disease. Here, Graham et al. identify 53 novel loci for eGFR in a GWAS meta-analysis, a subset of which are associated with other common diseases, such as diabetes and hypertension, based on PheWAS.

High-dimensional datasets derived from time-resolved live imaging of leukocytes in mice were used to identify leukocyte identities and dynamic neutrophil states with high cellular resolution.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.