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The authors have applied an eight-tissue rat multi-omic dataset to analyze the gene regulatory landscape of endurance exercise training, identifying tissue-specific regulatory patterns involved in muscle function, metabolism and immune response.

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.

Divergent white matter metabolic patterns reveal a mechanistic basis for cognitive resilience and enhance prediction of future cognitive decline beyond established aging and dementia biomarkers.

Single-variant and ultrarare variant burden analyses leveraging exome sequencing data from 22 cohorts identify new risk genes for amyotrophic lateral sclerosis and show cumulative effects of several rare variants on disease risk.

Longitudinal metatranscriptomics in a prospective cohort of 1,164 adults hospitalized for COVID-19 reveals that azithromycin offered no apparent anti-inflammatory benefit but enriched the respiratory microbiome with potential pathogens and antimicrobial resistance genes.

Genetic analyses in more than 15,000 individuals from across the Americas, including individuals with autism and family members, define the genetic landscape of autism in Latin American populations and identify significant overlap with other ancestries.

Parsimonious deep neural network models can be used for prediction of visual neuron responses.

Over five years, implementation of the NHS England Lung Cancer Screening Programme achieved high early-stage detection rates and demonstrated that the programme is both feasible and scalable for reaching high-risk and underserved populations.

The effectiveness of marine protected areas remains uncertain. Studying 2,800 tropical reefs, the authors of this study show that marine protected areas have compensated for only a small portion of human impacts on fish contributions to people and nature, particularly in terms of biomass and biodiversity.

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.

The first-in-human clinical trial of the LRRK2-targeting antisense oligonucleotide BIIB094 in Parkinson’s disease demonstrates that the treatment is well tolerated and produces dose-dependent reductions in cerebrospinal fluid levels of LRRK2 and phosphorylated Rab10, indicating successful target engagement.

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.

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.

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.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

Circulating tumor cell (CTC) clusters are key drivers of metastasis, yet their formation in tumors lacking classical adhesion molecules is unclear. Here, the authors discover that hyaluronic acid promotes homotypic and heterotypic CTC clustering by initiating early cell contacts and stabilizing mature interactions.

The authors find that TDP-43 loss of function—the pathology defining the neurodegenerative conditions ALS and FTD—induces novel mRNA polyadenylation events, which have different effects, including an increase in RNA stability, leading to higher protein levels.

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.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Nechanitzky et al. examine the cell-intrinsic role of choline acetyltransferase (ChAT)-expressing B cells in germinal center immune responses.

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.

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.

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.

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.

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

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.

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.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

HIV-1 integrase forms an RNA-binding module on the luminal side of the mature capsid lattice.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Landward barrier migration facilitates erosion of shoreface-exposed marsh and lagoon carbon stocks at rates outpacing backbarrier carbon accumulation, thus demonstrating the ephemeral nature of blue carbon storage along transgressive coasts.

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.

Conventional models treat hydrothermal gold and magmatic sulfide systems as unrelated. Here, the authors show that coeval deposits share isotopic and metal signatures, implying a common origin from a hydrous, fertile lithospheric mantle that has been modified by crustal recycling.

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.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Mosquitoes are major vectors for the transmission of many serious pathogens. This study uses genome-wide CRISPR screens in the mosquito, Anopheles gambiae, to reveal new insights into mosquito fitness and the function of clodronate-liposome mediated immune cell ablation.

Here the authors combine clinical and metabolomics data to identify distinct metabotypes of pediatric metabolic dysfunction-associated steatotic liver disease (MASLD). The results provide information regarding heterogeneity of MASLD presentation, but require validation in independent cohorts.

Scenario ensembles are widely used in climate change research, while their opportunistic nature could lead to biased outcomes in following analysis. Focusing on relevance, quality and diversity, researchers develop a simple and transparent weighting framework to address these challenges.