Genomics

RNA sequencing reveals widespread transcriptomic changes across the cerebral cortex in autism spectrum disorder, including primary sensory regions, in addition to association regions, as well as an attenuation of regional identity.

Which combination of current genome sequencing and assembly approaches results in high-quality, complete diploid genome assemblies is determined.

A study examining DNA transfer from mitochondria to the nucleus using whole-genome sequences from 66,083 people shows that this is an ongoing dynamic process in normal cells with distinct roles in different types of cancer.

A new phylogenomic method is developed that can detect recombinations in virus lineages in pandemic-scale datasets.

Sequencing of individual human lymphocyte clones shows that they are highly prone to mutations, with higher burdens in memory cells than in naive cells arising from mutational processes associated with differentiation and tissue residency.

cis-RNA editing quantitative trait loci, which are associated with immunogenic double-stranded RNAs, underlie genome-wide association study variants in common autoimmune and inflammatory diseases.

High-quality diploid assemblies of potato genomes from 24 wild and 20 cultivated potatoes provide insights into the complex evolution and diversity of potatoes, and could have applications in the breeding of hybrid potatoes.

A precise catalogue of more than 19 million variants from 838 tomato genomes, including 32 new reference-level genome assemblies, advances the understanding of the heritability of complex traits and demonstrates the power of the graph pangenome in crop breeding.

The systematic categorization of human enhancers by their cofactor dependencies provides a conceptual framework to understand the sequence and chromatin diversity of enhancers and their roles in different gene-regulatory programmes.

Haematopoiesis has high clonal diversity up to about 65 years of age, after which diversity drops precipitously owing to positive selection acting on a handful of clones that expand exponentially throughout adulthood.

Assembly and analysis of the Schmidtea mediterranea genome indicate that this planarian’s chromosome 1 may be evolving into a sex chromosome.

Assembly of the hexaploid oat genome and its diploid and tetraploid relatives clarifies the evolutionary history of oat and allows mapping of genes for agronomic traits.

A single-cell Poisson model is used to analyse eQTLs in memory T cells across continuous, dynamic cell states, revealing that the cell context is critical to understanding variation in eQTLs and their association with disease.

Natural variation in the mouse gene Mutyh influences the rate of C>A germline mutations.

A study of 21,879 families with rare genetic diseases identifies 12 with 2- to 7-fold excess of germline mutations, most of which are due to DNA repair defects or exposure to mutagenic chemotherapy, although most individuals with a hypermutated genome will not have a genetic disease.

Analyses of single-cell whole-genome sequencing data show that somatic mutations are increased in the brain of individuals with Alzheimer’s disease compared to neurotypical individuals, with a pattern of genomic damage distinct from that of normal ageing.

Whole-genome sequencing is used to analyse the landscape of somatic mutation in intestinal crypts from 16 mammalian species, revealing that rates of somatic mutation inversely scale with the lifespan of the animal across species.

An approach that combines deep mutational scanning with neural network-based thermodynamic modelling is used to provide comprehensive maps of the energetic and allosteric effects of mutations in two common protein domains.

A framework for studying and engineering gene regulatory DNA sequences, based on deep neural sequence-to-expression models trained on large-scale libraries of random DNA, provides insight into the evolution, evolvability and fitness landscapes of regulatory DNA.

TDP-43 controls an exon splicing event in UNC13A that results in the inclusion of a cryptic exon associated with frontotemporal dementia and amyotrophic lateral sclerosis.

A study describes single-cell characterization of the human cerebrovasculature, revealing human-specific transcriptomic signatures and providing insights into transcriptional changes associated with Huntington’s disease.

Analyses of circulating cell-free RNA (cfRNA) in blood samples from pregnant mothers identify changes in gene expression that could be used in liquid biopsy tests to identify and monitor individuals who are at risk of preeclampsia.

The BAF chromatin-remodelling complex ATPase gene Brm safeguards cell identity during directed cardiogenesis of mouse embryonic stem cells.

A technique using barcoded beads for DNA sequencing within tissue sections enables spatial resolution of tumour clonal heterogeneity and can be multiplexed with other analytical techniques for analysis of complex cellular phenotypes.

In this Perspective, a group representing a range of stakeholders makes the case for a set of five proposed globally applicable ethical guidelines for ancient human DNA research.

A large-scale metagenomic analysis of plant and mammal environmental DNA reveals complex ecological changes across the circumpolar region over the past 50,000 years, as biota responded to changing climates, culminating in the postglacial extinction of large mammals and emergence of modern ecosystems.

Whole-genome sequencing analysis of somatic mutations in liver samples from patients with chronic liver disease identifies driver mutations in metabolism-related genes such as FOXO1, and shows that these variants frequently exhibit convergent evolution.

A comprehensive atlas of cell types and regional specializations in the mouse cerebellar cortex.

A comprehensive survey of the epigenome from 45 regions of the mouse cortex, hippocampus, striatum, pallidum and olfactory areas using single-nucleus DNA methylation sequencing enables identification of 161 cell clusters with distinct locations and projection targets and provides insights into the regulatory landscape underlying neuronal diversity and spatial regulation.

Analysis of genomic networks from 430 modern individuals across 21 Pacific island populations reveals the human settlement history of Polynesia.

Somatic mutations obtained from laser microdissected biopsies of human tissues are used to reconstruct the developmental phylogenies of these tissues back to the zygote.

Whole-genome sequencing of haematopoietic colonies from human fetuses reveals the somatic mutations acquired by individual progenitors, which are used as barcodes to construct a phylogenetic tree of blood development.

A high-quality bonobo genome assembly provides insights into incomplete lineage sorting in hominids and its relevance to gene evolution and the genetic relationship among living hominids.

The Vertebrate Genome Project has used an optimized pipeline to generate high-quality genome assemblies for sixteen species (representing all major vertebrate classes), which have led to new biological insights.

A revised, universal nomenclature for the vertebrate genes that encode the oxytocin and vasopressin–vasotocin ligands and receptors will improve our understanding of gene evolution and facilitate the translation of findings across species.

Comparative analysis of 162 genomes of Asgard archaea results in six newly proposed phyla, including a deep branch that is provisionally named Wukongarchaeota, and sheds light on the evolutionary history of this clade.

A trio-binning approach is used to produce a fully haplotype-resolved diploid genome assembly for the common marmoset, providing insight into the heterozygosity spectrum and the evolution of the sex-differentiation region.

NanoSeq is used to detect mutations in single DNA molecules and analyses show that mutational processes that are independent of cell division are important contributors to somatic mutagenesis.

The complete assembly of human chromosome 8 resolves previous gaps and reveals hidden complex forms of genetic variation, enabling functional and evolutionary characterization of primate centromeres.

Single-cell analysis of genomes from primary human breast tumours and cell lines shows that chromosomal aberrations continue to evolve during primary tumour expansion, resulting in a milieu of subclones within the tumour.

Phylogenies of human placental cells based on whole-genome sequencing of bulk samples and microdissections reveal extensive mutagenesis in placental tissue, and suggest that mosaicism is a typical part of normal placental development.

Siberian mammoth genomes from the Early and Middle Pleistocene subepochs reveal adaptive changes and a key hybridization event, highlighting the value of deep-time palaeogenomics for studies of speciation and long-term evolutionary trends.

The authors present EpiMap, a compendium that comprises 10,000 epigenomic maps across more than 800 biosamples for the annotation of genome-wide association study circuitry.

The genome of the biofuel crop switchgrass (Panicum virgatum) reveals climate–gene–biomass associations that underlie adaptation in nature and will facilitate improvements of the yield of this crop for bioenergy production.

A chromosome-quality genome of the lungfish Neoceratodus fosteri sheds light on the development of obligate air-breathing and the gain of limb-like gene expression in lobed fins, providing insights into the water-to-land transition in vertebrate evolution.

New reference genomes of the two extant monotreme lineages (platypus and echidna) reveal the ancestral and lineage-specific genomic changes that shape both monotreme and mammalian evolution.

Ancient DNA reveals genetic differences between stone-tool users and people associated with ceramic technology in the Caribbean and provides substantially lower estimates of population sizes in the region before European contact.

A high-throughput, chromosome-wide analysis of DNA looping reveals its contribution to the organization of chromatin, and provides insight into how nucleosomes are deposited and organised de novo.

Chromosome-scale sequence assemblies of 20 diverse varieties of barley are used to construct a first-generation pan-genome, revealing previously hidden genetic variation that can be used by studies aimed at crop improvement