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The human ICF 4 syndrome is caused by mutation of the chromatin remodeller LSH. Here, the authors show that LSH depletion disrupts the ability of histone variant macroH2A to insert into chromatin and silence transcription.

A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.

The Collaborative Association Study of Psoriasis, in partnership with the Genetic Association Information Network (GAIN), reports a genome-wide association study for psoriasis. They identify new replicated associations that highlight a role for the IL-23 and NF-κB pathways in psoriasis susceptibility.

Multi-ancestry genome-wide analyses identify new risk loci for age-related macular degeneration. Ancestry-specific analyses identify distinct effects at major risk loci, including smaller effect sizes for CFH risk alleles in haplotypes of African ancestry.

Prostate cancer (PrCa) involves a large heritable genetic component. Here, the authors perform multivariate fine-mapping of known PrCa GWAS loci, identifying variants enriched for biological function, explaining more familial relative risk, and with potential application in clinical risk profiling.

Rosalind Eeles and colleagues report meta-analysis of genome-wide association studies for prostate cancer and genotyping on the custom iCOGS array in 25,074 cases and 24,272 controls from 32 studies available in the PRACTICAL Consortium. They identify 23 new prostate cancer susceptibility loci, 20 of which are associated with both aggressive and non-aggressive disease.

Platelet aggregation is associated with myocardial infarction and stroke. Here, the authors have conducted a whole genome sequencing association study on platelet aggregation, discovering a locus in RGS18, where enhancer assays suggest an effect on activity of haematopoeitic lineage transcription factors.

Epithelial-to-mesenchymal transition (EMT) is a complex process regulated at multiple molecular levels. Here, the authors implement an analytic framework - PAMAF - to integrate data from twelve distinct omics modalities, which they use to understand the molecular changes and regulation during EMT in vitro.

Analyses of the TRACERx study unveil the relationship between tissue morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk of lung adenocarcinomas.

Modern networks are rarely independent, instead being coupled together with many others. Thus the failure of a small fraction of nodes in one network may lead to the complete fragmentation of a system of several interdependent networks. Here, a framework is developed for understanding the robustness of interacting networks subject to such 'cascading' failures. Surprisingly, a broader degree distribution increases the vulnerability of interdependent networks to random failure.

African Americans have an elevated risk of developing chronic kidney disease, yet only a fraction of those with high-risk genotypes develop the disease. Here, the authors show that a missense variant in APOL1 has a strong protective effect when co-inherited with the high-risk G2 allele of APOL1, with important implications for clinical practice and translational research.

Cassava mosaic disease is caused by geminiviruses and suppresses cassava yields throughout the tropics. Here, the authors show that mutations in MePOLD1, encoding DNA polymerase δ subunit 1, co-segregate with CMD2, the major source of genetic resistance for this disease.

Werbowetski-Ogilvie, Taylor and colleagues report a noncanonical role for OTX2 in regulating alternative splicing and controlling a stem cell and pro-tumorigenic splicing program in group 3 medulloblastoma.

Koh et al. show that loci active in differentiated effector T cells are poised in early T precursors before the expression of T cell antigen receptors in a manner dependent on the chromatin remodeling complex mammalian SWItch/Sucrose Non-Fermentable and the PU.1–RUNX1 and BCL11B–RUNX1 complexes.

Montserrat Garcia-Closas and colleagues report a genome-wide association study for bladder cancer. They identify three new susceptibility loci on chromosomes 22q13.1, 19q12 and 2q37.1.

Major histocompatibility complex (MHC) loss of heterozygosity, allele-specific mutation and measurement of expression and repression (MHC Hammer) detects disruption to human leukocyte antigens due to mutations, loss of heterogeneity, altered gene expression or alternative splicing. Applied to lung and breast cancer datasets, the tool shows that these aberrations are common across cancer and can have clinical implications.

Fusion of rice Pong transposase to the Cas9 or Cas12a programmable nucleases provides sequence-specific targeted insertion of enhancer elements, an open reading frame and gene expression cassette into the genome of the model plant Arabidopsis and crop soybean.

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

There are dynamic interactions between immune cells and β cells that lead to β cell destruction in the context of autoimmune diabetes. Here the authors show that TET2, a methylcytosine dioxygenase, can regulate this interaction and deletion of TET2 can prevent the autoimmune destruction of β cells in mice.

Whole-genome sequencing of chronic lymphocytic leukemia from 485 patients identifies putative coding and noncoding drivers of disease. Genomically defined subgroups show distinct clinical and biological characteristics.

Immature thymic T cells receive signals through the T cell receptor which determine whether they undergo positive or negative selection. Calcineurin/NFAT signalling in preselection thymocytes produces a temporal window with enhanced signalling sensitivity paving the way for positive selection.

Ultrathin solar cells having thicknesses below 1 µm can still reach efficiencies comparable to their thicker counterparts, but require less material to manufacture. By exploiting light-trapping nanostructures, Chen and colleagues achieve GaAs solar cells with 20% efficiency at just 205 nm thicknesses.

Tracking data from 17 marine predator species in the Southern Ocean are used to identify Areas of Ecological Significance, the protection of which could help to mitigate increasing pressures on Southern Ocean ecosystems.

Studying the genetic progression of many cancers is difficult as longitudinal samples are rarely available. Here, the authors analyse a patient with chronic lymphocytic leukaemia over a 29 year period and track the clonal evolution of the patient’s disease and response to therapy.

Most studies of the genetics of the metabolome have been done in individuals of European descent. Here, the authors integrate genomics and metabolomics in Black individuals, highlighting the value of whole genome sequencing in diverse populations and linking circulating metabolites to human disease.

Ruth Halaban and colleagues report exome sequences of 147 melanoma tumors. They identified a recurrent somatic activating alteration in the Rho GTPase RAC1 in sun-exposed melanomas.

Analyses of multiregional tumour samples from 421 patients with non-small cell lung cancer prospectively enrolled to the TRACERx study reveal determinants of tumour evolution and relationships between intratumour heterogeneity and clinical outcome.

This is an Issue edsumm for 934. Identification of the Palaeocene/Eocene thermal maximum in a marine sedimentary sequence shows that sea surface temperatures near the North Pole increased from roughly 18 degrees Celsius to over 23 degrees Celsius — such warm values imply the absence of ice and thus exclude the influence of ice-albedo feedbacks on this Arctic warming.

Iris Heid, Gonçalo Abecasis, Sudha Iyengar and colleagues report the results of a large genome-wide association meta-analysis of macular degeneration based on over 43,000 subjects. They identify 16 new risk loci, including some very rare coding variants.

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.

Chromosome 8q24 is known to be a major susceptibility region for prostate cancer risk. Here the authors analyze genetic data across the 8q24 region from 71,535 prostate cancer patients identifying 12 risk loci, three previously unreported, highlighting the contribution of germline variation at this locus.

Emmanuel Mignot and colleagues report that variants in the T-cell receptor alpha (TRA@) locus are strongly associated with narcolepsy. This is the first documented involvement of the TCR locus in human disease and will shed light on how HLA-TCR interactions contribute to organ-specific autoimmune targeting.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

Physical dynamical processes can be modelled with differential equations that may be solved with numerical approaches, but this is computationally costly as the processes grow in complexity. In a new approach, dynamical processes are modelled with closed-form continuous-depth artificial neural networks. Improved efficiency in training and inference is demonstrated on various sequence modelling tasks including human action recognition and steering in autonomous driving.

Samples of different body regions from hundreds of human donors are used to study how genetic variation influences gene expression levels in 44 disease-relevant tissues.

A phase I dose-escalation trial of GD2-CAR T cells in children and young adults with diffuse midline gliomas to assess the feasibility of manufacturing, safety and tolerability, and to preliminarily assess efficacy.

Prostate cancer often does not progress to invasive disease and thus markers predicting the course of the disease progression are critical for optimal treatment choices. Here the authors show that variants at two genetic loci correlate with the aggressiveness of prostate cancer.

Psoriasis is an immune-mediated skin disease with a complex genetic architecture. Here, Elder and colleagues identify 16 novel psoriasis susceptibility loci using GWAS meta-analysis with a combined effective sample size of over 39,000 individuals.

Mixed responses to targeted therapy within a patient are a clinical challenge. Here the authors show that TP53 loss-of-function cooperates with whole genome doubling which increases chromosomal instability. This leads to greater cellular diversity and multiple routes of resistance, which in turn promotes mixed responses to treatment.

Much of the nutrient transport from the deep ocean into the ocean’s upper water column occurs through the Southern Ocean, with mixing and advection playing complementary roles, according to a box model analysis of the isotopic composition of ocean nitrate.

Innate T cells (ITC) contain many subsets and are poised to promptly respond to antigens and pathogens, but how this poised state is maintained is still unclear. Here the authors perform single-cell RNA-seq to align the various ITC subsets along an ‘innateness gradient’ that is associated with changes in proliferation and effector functions.