Reviews & Analysis

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  • We constructed a pan-genome using 27 high-quality representative Brassica oleracea genomes. Using this pan-genome, together with multi-omics datasets from large-scale populations, we uncovered the important role of structural variations as dosage regulators of gene expression, which drives the morphotype diversification in B. oleracea.

    Research Briefing
  • A common architectural feature of the genome in many organisms is chromatin domains. A synthetic biology approach now builds chromatin domains from scratch and identifies some of the minimal components needed for their formation.

    • Theodore Busby III
    • Tom Misteli
    News & Views
  • Understanding clinical heterogeneity in attention deficit hyperactivity disorder (ADHD) is important for improving personalized care and long-term outcomes. A study exploits the large scale and breadth of phenotyping of the iPSYCH cohort to link clinical heterogeneity to genetic heterogeneity in ADHD.

    • Chloe X. Yap
    • Jacob Gratten
    News & Views
  • This Review explores mechanistic theories of aging, discusses challenges in establishing causality of these mechanisms and suggests that genetically informed investigation will help address this gap.

    • João Pedro de Magalhães
    Review Article
  • Skin color is highly variable in Africans, but the underlying molecular mechanisms remain poorly understood. Using population genetics and functional genomics, we identified key genetic variants, regulatory elements and genes that affect skin pigmentation, an adaptive trait, which provides valuable insights into the mechanisms underlying human skin color diversity and evolution.

    Research Briefing
  • The genetic background of pediatric acute myeloid leukemia (AML) does not fit with classification systems developed for adult AML. This study investigates the genetic background of pediatric AML and proposes a genomic framework for improved classification and risk stratification based on the driver alterations.

    Research Briefing
  • The spatial biology revolution promises deep insights into tissue organization, but deriving this knowledge from diverse, complex data remains a major obstacle. Data-driven discovery of the multicellular organization of tissues is now achieved by transforming multimodal spatial imaging data using deep learning.

    • Ellen Schrader
    • H. Raza Ali
    News & Views
  • A new study combining experimental treatments of human blood cells from thousands of individuals with flow-cytometry-based phenotyping and then genome-wide association analyses identifies genetic loci associated with non-resting cell states. Integrating the results with disease association signals yields insights into the underlying biology.

    • Andrew D. Johnson
    News & Views
  • Polymorphisms in the non-coding genome affect genetic circuits and result in variable immune responses across individuals. Here we report a genetic circuit involving a long non-coding RNA (lncRNA) that spatially coordinates chromatin contacts to control pro- and anti-inflammatory gene expression and shape immune responses of healthy individuals to pathogens or vaccination.

    Research Briefing
  • New research reports that paused RNA polymerase II (RNAPII) enhances the targeting and activity of BAF chromatin remodelers. These findings suggest a new paradigm for understanding how the collaborative action of chromatin remodelers and the transcriptional machinery govern cell-type-specific chromatin accessibility.

    • Brent Y. Chick
    • Diana C. Hargreaves
    News & Views
  • CX-5461 (also known as pidnarulex), currently in phase 1/2 trials, induces selective killing of homologous-recombination-deficient or BRCA1- or BRCA2-mutated tumors in preclinical models. New work confirms these findings but shows it to be a remarkably potent mutagen that induces extensive genetic changes in cultured human cells with or without BRCA1/2 mutations, raising substantial safety issues.

    • Simon J. Boulton
    News & Views
  • Long segments of the genome that are shared ‘identical by descent’ (IBD) demonstrate recent relatedness between individuals. A new computational method robustly identifies shared IBD segments in human ancient DNA data, providing insights into the mobility and demography of prehistoric human societies.

    • Anders Bergström
    News & Views
  • EasySci, a scalable single-cell profiling technique, uncovered over 300 mammalian brain cell states, revealing molecular features and dynamics of rare cell states linked to aging and Alzheimer’s disease. This work offers insights into cell states that expand (rare astrocytes and vascular leptomeningeal cells in the olfactory bulb, reactive microglia, and oligodendrocytes) or are depleted (neuronal progenitors, neuroblasts and committed oligodendrocyte precursors) during normal and pathological aging.

    Research Briefing
  • Combined analysis of genome-wide association studies and epigenetic data has identified certain immune cell types as drivers of autoimmune disease, but current methods have not been able to pinpoint key effector immune cell states. Using single-cell data from inflammatory tissues, we identified effector cell states embedded within inflammatory tissues — including T peripheral helper cells and tissue regulatory T cells — that capture disproportionate disease heritability.

    Research Briefing
  • We present a model to predict the chance of each possible de novo mutation in the human genome informed by recent insights into determinants of mutagenesis. Predictions were applied to refine demographic models, identify constrained genes, and uncover mutagenic effects of polymerase III transcription and transcription factor binding in testis.

    Research Briefing
  • Variants in the HLA region on chromosome 6 are strongly associated with many immune-related diseases. A method to construct personalized HLA genomes from single-cell RNA sequencing data, coupled with single-cell HLA expression quantitative trait loci modeling, identifies how genetic variants influence HLA gene expression across cell states.

    • Jennifer A. Kelly
    • Kandice L. Tessneer
    • Patrick M. Gaffney
    News & Views
  • This Perspective article explores complex synthetic lethal relationships in cancer, which can involve several partners. Understanding this complexity presents challenges and opportunities for the development of therapeutics that target these interactions.

    • Colm J. Ryan
    • Lovely Paul Solomon Devakumar
    • Christopher J. Lord
  • Whole-genome sequencing data of individuals from the UK Biobank and Iceland and a somatic mutation barcoding strategy enabled detection of clonal hematopoiesis at scale. This comprehensive study provides insights into the epidemiology, somatic and germline genetics, and disease associations of clonal hematopoiesis.

    Research Briefing