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Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

From 2014–2017, marine heatwaves caused global mass coral bleaching, where the corals lose their symbiotic algae. The authors find, this event exceeded the severity of all prior global bleaching events in recorded history, with approximately half the world’s reefs bleaching and 15% experiencing substantial mortality.

Genetic mapping in mice identified Homer1a as a key modifier of attention. Developmental downregulation in the prefrontal cortex enhances inhibitory tone, neural signal to noise and adult attentional performance, revealing a new control mechanism and target.

Whole-genome sequencing of polioviruses in Uganda following nOPV2 use showed high genetic stability and no sustained transmission, even though a rare double recombinant strain regained virulence, but did not spread due to high vaccination coverage.

Analysing the causal links of gene expression and protein abundance on type 2 diabetes risk in blood and seven tissues related to the disease from individuals of four ancestries, the authors advance our understanding of the genetic architecture of type 2 diabetes

Deconvolution methods infer levels of immune infiltration from bulk expression of tumour samples. Here, authors assess 6 published and 22 community-contributed methods via a DREAM Challenge using in vitro and in silico transcriptional profiles of admixed cancer and healthy immune cells.

Little millet is an orphan crop offering a promising yet underutilized option in the pursuit of food and nutritional security. Here, the authors report its genome assembly, and elucidate its recent tetraploid structure, sub-genome dominance, and the genetic basis for micronutrient content.

A cost-aware AI framework facilitates the development of predictive AI models that optimize the trade-off between prediction performance and feature cost.

Semiconductor-based, non-optical DNA sequencing technologies such as Ion Torrent sequencing offer speed and cost advantages compared with alternative techniques. Cheng et al. demonstrate a protocol allowing the use of Ion Torrent technology to sequence DNA from chromatin immunoprecipitation experiments.

Different functional variants in ADH1B (and elsewhere) in Europeans and Africans strongly affect risk for alcohol dependence. Dependence only partly genetically correlates with consumption, with strong correlations to other psychiatric disorders.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

mRNA vaccines targeting SARS-CoV-2 also sensitize tumours to immune checkpoint inhibitors.

Long-read sequencing enables high-quality genome assemblies, but challenges remain. Here, the authors introduce Cornetto, a method that improves assembly quality, enables genome sequencing from saliva, and accurately resolves medically-relevant repetitive genes.

Analysis of whole-genome sequence data from 3,474 families finds an excess of private, likely gene-disrupting variants in individuals with autism. These variants are under purifying selection and suggest candidate genes not previously associated with autism.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

High-fidelity reads improve variant detection and genome assembly on the PacBio platform.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving 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.

Sequencing data from two large-scale studies show that most of the genetic variation influencing the risk of type 2 diabetes involves common alleles and is found in regions previously identified by genome-wide association studies, clarifying the genetic architecture of this disease.

The Vertebrate Genome Project has used an optimized pipeline to generate high-quality genome assemblies for sixteen species (representing all major vertebrate classes), which have led to new biological insights.

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.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

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.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

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.

Smartphone sensors that monitor disease symptoms enable remote assessment of Parkinson’s patients.

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.

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.

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.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

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.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

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.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

Somatic small variants in cancer genomes are identified in both short-read and long-read data.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

Sagar et al. show that human sniff behaviour is sensitive to the perceptual characteristics of the odour being detected.

Determining the extent of immune cell infiltration into solid tumours is essential for adequate therapeutic response. Here the authors develop a DNA methylation-based approach for tumour cell fraction deconvolution and analyse tumour composition and genomics across a wide spectrum of solid cancers.