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When 100 social and behavioural science claims were examined, 34% of reanalyses closely matched the original results, with 74% reaching the same conclusion, revealing limited robustness of single-path analyses and the need to address analytical uncertainty.

AlphaFold’s success in protein structure predictions has led to similar attempts to predict interactomes. Here, the authors demonstrate that AI-based screens are very limited in discovering truly novel interactions compared to experimental screens, exposing open challenges in interaction prediction.

Here, the authors identify geranylgeranoic acid (GGA), a polyunsaturated fatty acid with anti-adhesive activity against clinical isolates of multidrug-resistant Staphylococcus aureus and efficacy against skin and soft tissue infections in mice.

Wild meat is a fundamental component of the diets of rural Central African populations, accounting for 20% of the recommended daily protein intake, compared with 13% and 6% for those living in towns and cities.

DNA-sequencing data from primary tumours and paired metastases from participants in the TRACERx lung study and PEACE autopsy programme are used to analyse the metastatic diversity of advanced non-small cell lung cancer and the seeding patterns that underpin it.

RNA velocity is a widely used method to predict the fate of single cells. Here the authors show that the concept can be adapted to predict the fate of individual human subjects, using RNA velocity of whole blood at a single point in time to predict future clinical outcomes and treatment responses.

A large-scale study on the replicability of claims from social and behavioural science journals reports that about half of the results replicate in the same patterns as the original study.

Higher-order interactions are shown to contribute to the decrease in species diversity from low to high latitudes in global forests, potentially explaining why this intricate phenomenon cannot be adequately explained by pairwise interactions alone.

Analysis of northern elephant seal populations shows no evidence of inbreeding depression, probably because a recent extreme bottleneck purged much of the genetic load.

Extracellular vesicles from lung epithelial cells deliver ACE2 and TMPRSS2 to recipient cells, enabling SARS-CoV-2 infection beyond receptor-expressing cells and expanding viral tropism.

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.

Snyder et al. analyze two population-based birth cohorts to test associations of newborn metabolite concentrations and childhood respiratory outcomes. C4, C10:1, C18:2, and citrulline are associated with early-life wheezing and asthma, with C18:2 specifically associated with increased non-allergic asthma risk.

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.

Multi-ancestry GWAS meta-analysis identifies risk loci for severe nausea and vomiting of pregnancy. Downstream analyses explore maternal and fetal contributions of these loci and their temporal effects.

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.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

DNA demethylation enzyme TET1 is a known oncogene in leukemia. Here, the authors discover that TET1 is involved in GPX4-dependent and -independent ferroptosis in acute myeloid leukemia via the regulation of GSH synthesis enzyme GCLC and BH4 synthesis enzyme GCH1.

Robustness checks and reproduction of analyses with existing and updated data based on 110 articles in economics and political science journals with data and code-sharing requirements found high levels of robustness and reproducibility and determined that robustness was not dependent on author characteristics or data availability.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

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.

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.

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.

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.

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

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.

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 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.

The impact of various infectious agents on human survival and reproduction over thousands of years has exerted selective pressure on numerous regions of the human genome. This Review describes how such signatures of selection can be detected and integrated with data from complementary approaches, such as genome-wide association studies, to provide biological insights into host–pathogen interactions.

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.

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.

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.

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.

Single-nucleus chromatin and RNA sequencing identifies epigenetic chromatin domains that confer vulnerability to paediatric brain tumours such as ependymomas, providing insight into the development of such tumours despite ‘quiet’ genomes.

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.

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.

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.

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.

An analysis of whole-exome sequencing data linked to longitudinal electronic health records from 44,028 British South Asians finds new gene–phenotype associations and identifies 2,991 genes with rare biallelic predicted loss-of-function genotypes.

LncRNAs modulate diverse physiological cellular processes, however, their involvement in heme-dependent processes are not yet clear. Here the authors reveal the role of lncRNA UCA1 in erythroid cell development.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Climate change is altering how plants balance carbon gain and water loss. This study maps global leaf-level water-use efficiency over the past two decades, showing it is highest in regions that are cold or dry, increasing worldwide, and strongly influenced by atmospheric dryness.

Resistance to menin inhibitors often occurs in the initially sensitive MLL-rearranged (MLLr) leukemias. Here authors discover that inhibition of guanine nucleotide biosynthesis leads to myeloid differentiation and sensitization to menin inhibitors in leukemia stem cells of MLLr leukemia.