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Head motion is an artifact in structural and functional MRI signals, and some traits or groups are more strongly correlated with motion than others. Here the authors describe a method to attribute a motion impact score to specific trait-functional connectivity relationships.

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

Bioactivity-guided isolation of specialized metabolites is an iterative process. Here, the authors demonstrate a native metabolomics approach that allows for fast screening of complex metabolite extracts against a protein of interest and simultaneous structure annotation.

A complementary analysis of DESI DR2 distance measurements along with supernova and CMB data shows consistent, moderate evidence that dark energy changes over time rather than behaving as a simple cosmological constant.

A genome-wide CRISPR screen helps to identify the Epstein–Barr virus receptor desmocollin 2 for primary epithelial cell infection. Additional infection assays revealed that desmocollin 3 also aids infection.

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.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

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.

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.

Soil thickness is a key parameter in earth system models, yet how it varies spatially at catchment scales is largely unknown due to measurement challenges. Here, the authors show that a continuous field of thicknesses can be predicted using high-resolution topography and a few soil thickness measurements.

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.

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.

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 authors report resonant soft x-ray scattering and polarimetry measurements on epitaxial thin films of La3Ni2O7. They find a diagonal bicollinear double spin stripe order, with no evidence of charge modulation.

Condensates composed of the disordered region of the mediator of RNA polymerase II transcription subunit 1 (MED1) are known to partition specific proteins, but whether this specificity arises from ordered-structure-mediated or dynamic multivalent amino acid interactions remains unclear. Here, the authors show that a physics-based model that only accounts for multivalent polymer interactions is able to explain and predict selective partitioning, suggesting that the specificity of condensate composition is underpinned by multivalent interactions in the context of conformational disorder.

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).

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.

SCIFER detects clonal selection in whole-genome sequencing data using a population genetics model. Applied to a range of somatic tissues, SCIFER quantifies stem cell dynamics and infers clonal ages and sizes without requiring knowledge of driver events.

This study finds that decision markets can be a useful tool for selecting studies for replication. For a sample of 26 online experiments published in PNAS selected by a decision market, the authors find replication rates ranging between 54% and 62%.

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.

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.

When a Josephson junction is embedded into a highly-resistive environment, it loses its superconducting properties and starts to behave as an insulator. This results in voltage oscillations across the current-biased junction - the Bloch oscillations. Here the authors develop a fully quantum theory of this effect.

The Mass Spectrometry Query Language (MassQL) is an open-source language that enables instrument-independent searching across mass spectrometry data for complex patterns of interest via concise and expressive queries without the need for programming skills.

This study uncovered genetic associations with environmental sensitivity in psychiatric and neurodevelopmental traits in an international collaboration using data from more than 21,000 monozygotic twins—the largest genetic study of monozygotic twin differences to date.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

Marine bacteria opt for divergent foraging strategies when faced with carbon starvation—either cease motility entirely, or convert biomass to energy to retain motility.

Multisystem inflammatory syndrome in children (MIS-C) onsets in COVID-19 patients with manifestations similar to Kawasaki disease (KD). Here the author probe the peripheral blood transcriptome of MIS-C patients to find signatures related to natural killer (NK) cell activation and CD8+ T cell exhaustion that are shared with KD patients.

In the phase 2 study LCCC1520 (NCT02690558), clinical activity of pembrolizumab in combination with gemcitabine and cisplatin as neoadjuvant therapy in patients with muscle-invasive bladder cancer has been reported. Here the authors present molecular and immune cellular features associated with response to neoadjuvant chemo-immunotherapy.

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.

Michael Talkowski, David FitzPatrick, Erica Davis and colleagues report rare inherited or de novo missense variants in SMCHD1 in arhinia patients. Some of the same mutations in SMCHD1 are known to cause a phenotypically distinct muscular dystrophy disorder, FSHD2, and the distinct clinical features of the two disorders suggests that additional genes interact with SMCHD1 to cause arhinia.

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.

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.

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.

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.

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.

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.

Harty and colleagues report that physiological microbial exposures in mice can enhance memory T cell presence in the brain and influence neurological disease outcomes.