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Genomic analyses of DNA from modern individuals show that, about 800 years ago, pre-European contact occurred between Polynesian individuals and Native American individuals from near present-day Colombia, while remote Pacific islands were still being settled.

A candidate-based genetic screen in Drosophila expressing 30 G₄C₂-repeat-containing RNAs finds that RanGAP, a key regulator of nucleocytoplasmic transport, is a potent suppressor of neurodegeneration; the defects caused by the G₄C₂ repeat expansions can be rescued with antisense oligonucleotides or small molecules targeting the G-quadruplexes.

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.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

Understanding how cells differentiate to their final fates is a fundamental biological problem. Here, authors introduce MultiVeloVAE, a probabilistic framework that models gene expression and chromatin accessibility mechanistically, integrates multiple samples, accounts for bifurcations, and enables statistical testing over time.

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.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

The host microbiome may influence asthma susceptibility differently across diverse geographic or ethnic populations. Here the authors perform a microbiome study of asthma in US Hispanic/Latino adults and evaluate the influence of obesity and genetic factors on the relationship between microbiome characteristics and asthma.

A method that allows for the detection of mosaic chromosomal alterations from blood whole-genome sequencing data highlights ancestry-specific differences in the distribution of common and rare germline susceptibility variants.

Wang, Huang, Nelson, Gao, and colleagues perform a head-to-head comparison of multiple platforms for imaging spatial transcriptomics, determining their relative sensitivity, specificity, and ability to identify major cell types in clinical pathology samples.

Using experimental and computational approaches the authors show that the vestibular efferent system does not modulate peripheral coding during locomotion. Instead, vestibular afferents unambiguously convey information in a context independent manner.

Analysis of whole-genome sequences of 25,465 individuals of European ancestry shows that rare variants contribute substantially to the heritability of height and body mass index.

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

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

Here the authors conduct a multi-ancestry meta-analysis of telomere length, used diverse approaches to identify genes underlying association signals, and experimentally validated POP5 and KBTBD6 as regulators of telomere length in human cells.

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.

A Middle Triassic diapsid is presented that has a distinctive crest consisting of integumentary appendages that are structurally distinct from avemetatarsalian feathers.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

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 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.

Whole-genome sequencing and phenotype data sharing are introduced in a national health system to streamline diagnosis and to discover coding and non-coding variants that cause rare diseases.

Without rapid change, the World Health Organization’s goals for tackling cervical cancer by 2030 will be missed. Four experts share ways to move the needle.

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.

Human papillomavirus (HPV) DNA testing is the preferred method for cervical cancer screening, but existing tests are inaccessible for resource-limited settings. Here, authors develop a low-cost, simple HPV DNA assay suitable for bedside testing and demonstrate strong performance in Mozambique.

Colorectal cancer metastasis involves dramatic plasticity and loss of PROX1-mediated repression of non-intestinal lineages.

How our genes and environment determine our vulnerability to SARS-CoV-2 infection and the severity of COVID19 remains uncertain. Here, the authors find that as the pandemic progressed the relative importance of genetic variation increased, highlighting the dynamic nature of heritability amidst changing public policies and vaccination rates.

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 future of carbon dynamics in the northern high latitudes is uncertain yet represents an important potential feedback under climate change. This study uses a comprehensive observational dataset to show an increasing carbon sink in non-permafrost systems; in permafrost systems uptake was offset by loss.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

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.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

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.

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.

Melinda Mills, Nicola Barban, Harold Snieder, Marcel den Hoed and colleagues perform a meta-analysis of data from over 300,000 individuals for age at first birth and number of children ever born. They identify 12 significant loci that associate with these traits, providing insights into the genetic basis of human reproductive behavior.

The Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) aims to better understand population genetics of the African diaspora. Here, it uses deeply sequenced whole-genomes to describe the impact of admixture and potential disease burden of deleterious variants.

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.

Using a globally coordinated strategic conservation framework to plan an increase in ocean protection through marine protected areas can yield benefits for biodiversity, food provisioning and carbon storage.

The genomic profile and early transmission dynamics of the Omicron strain of SARS-CoV-2.

Longitudinal multi-omics measurements are highly valuable in studying heterogeneity in health and disease phenotypes. Here, the authors apply Pareto Task Inference to analyze the clinical lab tests of 3094 individuals and find three wellness states, and one aberrant health state defining this cohort.

Single-nucleus and single-cell RNA sequencing plus spatial profiling with four methods of core biopsies from 60 patients with metastatic breast cancer reveal patient-specific gene expression programs of breast cancer metastases that are maintained across time, site of metastasis and spatial profiling method, with spatial phenotypes correlating with microenvironmental features.

A rare case of asymptomatic dominantly inherited Alzheimer’s reveals confined tau pathology and unique proteomic features, highlighting potential resilience mechanisms decades beyond expected onset.

In a prospective study involving 92 physicians from multiple institutions, access to large language model assistance on top of conventional resources increased a score expressing the quality of their reasoning in addressing patient care while assessing five clinical vignettes.

Single-cell chromatin profiling of different brain regions identifies cell-type-specific regulatory elements, and helps to predict functional SNPs for Alzheimer’s and Parkinson’s diseases.

Sei is a new framework for integrating human genetics data with a sequence-based mapping of predicted regulatory activities to elucidate mechanisms contributing to complex traits and diseases.

A strategy for inferring phase for rare variant pairs is applied to exome sequencing data for 125,748 individuals from the Genome Aggregation Database (gnomAD). This resource will aid interpretation of rare co-occurring variants in the context of recessive disease.