Search

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.

Heterochronic parabiosis ameliorates age-related diseases in mice, but how it affects epigenetic aging and long-term health was not known. Here, the authors show that in mice exposure to young circulation leads to reduced epigenetic aging, an effect that persists for several months after removing the youthful circulation.

Using pancreatic organoids and genetic mouse models, Antonucci et al. show that cellular stress activates an NRF2–EZH2 epigenetic axis leading to metabolic reprogramming and subsequent malignant transformation of KRAS-mutant benign lesions.

The Tabulae Paralytica, a compilation of four molecular atlases of spinal cord injury, provides a window into the pathobiology of spinal cord injury, establishing a framework for integrating multimodal, genome-scale measurements in four dimensions to study biology and medicine.

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.

Placing particles at the interface between immiscible fluids usually enhances emulsification. However, now it is shown that if the particles are ferromagnetic, emulsification is suppressed and a non-planar recoverable interfacial shape develops.

Delval, Hantute-Ghesquier, Sencio and colleagues demonstrate that depletion of age-associated senescent cells decreases pulmonary viral load and ameliorates early and late lung COVID-19 in a hamster model of aging.

Clonal or isogenic model organisms allow for controlled replication, but their isolation from natural systems compromises their relevance for ecology and evolution research. However, a substantial number of vertebrate species reproduce clonally in nature and are an underused resource.

Much investment goes into improving police-community interactions, yet trust in police remains low. Here, the authors show that community members report feeling less threat and more trust when officers use transparency statements to start interactions.

Here the authors investigate the underlying genetic mechanisms for pathogenic variant carrier phenotype heterogeneity using exomes and clinical phenotypes from the UK and Mt. Sinai BioMe Biobanks and observed translational potential for all three mechanisms.

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.

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.

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.

Isolating and studying haematopoietic stem cells in young and aged mice demonstrates evolutionary processes related to blood production and provides a framework for interpreting future work using laboratory mice to study stem cell ageing.

Using stable isotopes, this study introduces an indicator of dynamic water retention that shows river flow dynamics are influenced by land use and hydroclimate characteristics, helping categorize catchment responses and improving water resource management.

In male mouse germline development, the precise DNA methylation of young, active transposons requires a two-step process in which SPIN1 and SPOCD1 mark young LINE1 elements before the piRNA pathway triggers DNA methylation.

Zhang et al. provide evidence that, during meiosis, recombination proteins assemble into active droplets, the coarsening of which partially explains the phenomenon of crossover interference.

Mutational signature analysis of blood cells isolated from 23 chemotherapy-exposed samples and 9 nonexposed controls characterizes the effects of various drugs on mutational burden, signature exposure and cell types.

Afshar, Dammer et al. identify plasma proteins associated with Alzheimer’s disease brain pathologies and find that many plasma proteins related to cognitive function are not associated with these pathologies.

Gene regulatory network architecture and complex dosage effects from paralogue diversification converge to shape phenotypic space, producing the potential for both strongly buffered phenotypes and sudden bursts of phenotypic change.

In many locations globally, wildfires are becoming more frequent, intense and/or larger in area compared with historical fire regimes. This Review discusses the factors that determine how species and ecosystems respond to changing fire regimes and outlines important conservation and management considerations.

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).

Recombination is a meiotic process that ensures accurate chromosome segregation. Here, the authors characterize recombination patterns in over 4,200 families. Their results show that recombination rate increases with maternal age, and highlight sex differences in the distribution of these events.

Maneix, Iakova and colleagues report that cyclophilin A is a chaperone for, and regulator of, intrinsically disordered proteins within haematopoietic stem and progenitor cells, with potential effects on ageing-like phenotypes and lineage commitment.

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.

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.

Lithium has an essential role in the brain and is deficient early in Alzheimer’s disease, which can be recapitulated in mice and treated with a novel lithium salt that restores the physiological level.

Natural products have historically made a major contribution to pharmacotherapy, but also present challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization. This Review discusses recent technological developments — including improved analytical tools, genome mining and engineering strategies, and microbial culturing advances — that are enabling a revitalization of natural product-based drug discovery.

Alarmone synthesis depletes GTP levels leading to a GTP-dependent switch that controls triggered, spontaneous and antibiotic-induced persister formation in Bacillus subtilis.

The COVID-19 pandemic has raised concerns about increased neuropsychiatric conditions in children and youths, with potential links to SARS-CoV-2 infection. Here, the authors analyze EHR data from 25 institutions, showing that COVID-19 positive children and youths have a modestly increased risk of developing neuropsychiatric conditions, such as anxiety, depression, and ADHD, compared to those who tested negative.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

Specific functions of viral helicases in genome replication of RNA viruses are widely unknown. This study suggests that hepatitis C virus NS3 helicase unwinds stem loop structures at the 3’end of the genome, thereby facilitating (−) strand synthesis.

Sex differences are well established in the prevalence and symptoms of depression. Here, the authors identify a novel X chromosome variant, greater genetic risk, and stronger links to metabolic traits in females, highlighting the importance of sex-aware approaches.

A comprehensive analysis of the cell-specific molecular regulatory mechanisms underlying post-traumatic stress disorder in the human prefrontal cortex.

Diet diversity across northern hemisphere ecosystems affects seabird responses to climate change, with breeding productivity declining in the Arctic and North Atlantic but not in the Pacific from 1993 to 2019, based on 138 time series of breeding success and linear mixed effects models.

Changes in the microenvironment of the aged lung relative to younger lung tissue can lead to the reactivation of dormant melanoma cells through a mechanism that involves a decrease in WNT5A and AXL signalling and an increase in MERTK.

Malaria chemoprevention is used for young children, but resistance mutations raise concerns on efficacy. In this analysis of trials across Africa, the authors show that prevention treatment protects >42 days against susceptible parasites but <12 days against highly resistant strains highlighting the importance of genomic surveillance for chemoprevention strategies.

A highly scalable approach is used to generate 3,000 genome-wide maps of transcription factor binding in ten flowering plants, along with multi-species single-nucleus RNA-seq atlases. Together, the results reveal both ancient regulation and key regulatory adaptations.

Proteomic analysis of paired cerebrospinal fluid and plasma samples from 2,171 individuals drawn from multiple cohorts, including the Global Neurodegeneration Proteomics Consortium, reveals age-related changes in the ratios of proteins in the cerebrospinal fluid and plasma that are associated with cognitive function, enhancing understanding of blood–brain barrier dynamics in aging.

Analyses of the genomes of cichlid species reveal that the combination of ecological opportunity, sexual selection and exceptional genomic potential is the key to understanding explosive adaptive radiation in cichlids.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

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.