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In this four-part podcast series, Nature follows two scientists to find what it takes to launch a research lab.

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.

Many genetic factors that contribute to uterine leiomyomata (UL) - the most common tumours of the female genital tract - remain to be discovered. Here, the authors conduct a UL meta-genome-wide association study, and find loci related to altered muscle tissue biology that are associated with UL.

Nature follows two scientists as they fight against the odds to build their careers.

In part two of a series, a pair of researchers race to secure the funding that will keep their operations going.

Protect time for deep thinking — it is crucial for productivity in a world of constant interaction, urges Heidi Rehm.

A genome-wide association study meta-analysis combined with multiomics data of osteoarthritis identifies 700 effector genes as well as biological processes with a convergent involvement of multiple effector genes; 10% of these genes express the target of approved drugs.

Just as two scientists manage to get their labs going, the COVID outbreak hits. Then comes a personal setback in part three of a series.

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.

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.

The human Fallopian tube (FT) is implicated as a site of origin for pelvic serous cancers. Here the authors conduct multi-omics analysis on over 100 FTs. The results challenge the assumption that BRCA1/2 mutation carriers exhibit significant molecular alterations in normal FTs before loss of heterozygosity (LOH) occurs, and suggest that tumorigenesis in BRCA1/2 carriers requires LOH or secondary genetic events rather than haploinsufficiency alone.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Fossils reveal the flightless birds' early migration to the tropics.

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.

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 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.

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.

Inhibition of cyclooxygenase 1 releases T cells from immunosuppression by platelet-derived thromboxane A₂, thereby enhancing the immune response against metastasis.

Genome-wide analyses identify variants associated with sinus node dysfunction, distal conduction disease and pacemaker implantation, implicating ion channel function, cardiac developmental programs and sarcomeric structure in bradyarrhythmia susceptibility.

Hundreds of orchid species lure their pollinators with the promise of sex, only to send them away unfulfilled. Heidi Ledford looks at how dishonesty gives them the evolutionary edge.

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.

Mouse study shows molecule controls blood sugar by hitting elusive drug target. 

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.

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 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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

Results can be thrust from bench to bedside, but there is also much to be learned by pushing the other way. Heidi Ledford tells tales of clinical trials that have prompted a change in tack.

The real power of the biological tool lies in exploring how genomes work.

Images slip unnoticed into the brain.

The structure of a spontaneously activated immune protein is determined by cryo-electron microscopy. This reveals the passage of an entire ___domain through a transient opening. The authors investigate the mechanism by multiple biophysical approaches.

A genomic constraint map for the human genome constructed using data from 76,156 human genomes from the Genome Aggregation Database shows that non-coding constrained regions are enriched for regulatory elements and variants associated with complex diseases and traits.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.

This manuscript evaluates forecasts of laboratory-confirmed influenza hospital admissions, a new target for influenza forecasting in the United States. Across two influenza seasons, the FluSight ensemble is robust compared to submitted models.

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.

Developmental and epileptic encephalopathies are devastating neurological disorders. Here, the authors establish a cohort of patients with variants in the gene DENND5A and use human stem cells to discover a disease mechanism involving altered cell division.

Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is a heterogeneous and aggressive type of T-cell lymphoma. Here, the authors perform single-cell analyses of human and murine PTCL-NOS tumors, and identify a subtype defined by the loss of SMARCB1 that could be targeted with HDAC-inhibitor combination therapies.

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.