Search

Here, the authors integrate genomic, proteomic, and phenotypic data from UK Biobank, identifying over 1,100 gene-environment interactions. They catalogue interactions between 101 blood proteins and 153 exposures, which may refine biomarker discovery.

Laser microdissection and microarrays are used to assess 900 precise subdivisions of the brains from three healthy men with 60,000 gene expression probes; the resulting atlas allows comparisons between humans and other animals, and will facilitate studies of human neurological and psychiatric diseases.

Pooled CRISPR perturbation screens with multimodal RNA and protein single-cell profiling readout (Perturb-CITE-seq) applied to patient-derived melanoma and tumor-infiltrating lymphocyte co-cultures identifies new tumor immune evasion mechanisms.

Neural Decomposition (NEURD) is a software package that decomposes neuronal data from high-resolution electron microscopy volumes into feature-rich graph representations to facilitate analysis for neuroscience research.

Using volumetric electron microscopy, the authors map and analyze the structure of cortical inhibition with synaptic resolution across a column of visual cortex.

Computational and machine-learning approaches that integrate genomic and transcriptomic variation from paired primary and metastatic non-small cell lung cancer samples from the TRACERx cohort reveal the role of transcriptional events in tumour evolution.

Aarrestad et al. show that, in contrast to psychedelics, the nonhallucinogenic psychoplastogen tabernanthalog promotes neuroplasticity through 5-HT_2AR activation without immediately increasing extracellular glutamate levels or immediate early gene expression.

This report from the 1000 Genomes Project describes the genomes of 1,092 individuals from 14 human populations, providing a resource for common and low-frequency variant analysis in individuals from diverse populations; hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites, can be found in each individual.

Many current immunoassays require multiple washing, incubation and optimization steps. Here the authors present Ratiometric Plug-and-Play Immunodiagnostics (RAPPID), a generic assay platform that uses ratiometric bioluminescent detection to allow sandwich immunoassays to be performed directly in solution.

This analysis of individuals of admixed genetic ancestries suggests that complex trait causal variant effect sizes are, by and large, similar across ancestries, and discusses the implications for the study of these and other diverse populations.

Protein changes in a brain with Alzheimer’s are not often accompanied by transcriptional differences. Here, using a deep neural network that predicts protein abundance from mRNA expression, the authors track the early protein changes in Alzheimer’s dementia.

Chris Spencer, Eleanor Barnes and colleagues use human genotyping arrays and whole-genome viral sequencing to perform a systematic genome-to-genome study of 542 individuals chronically infected with hepatitis C virus (HCV). They show that both HLA alleles and genes encoding factors of the innate immune system drive viral genome polymorphism and that IFNL4 genotypes determine HCV viral load through a mechanism dependent on a specific polymorphism encoded in the HCV polyprotein.

Immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS) infers B cell and T cell fractions from whole-genome sequencing data. Applied to the 100,000 Genomes Project datasets, circulating T cell fraction provides sex-dependent and prognostic insights in patients.

The number of job applications and identifying as a woman have been determined as success factors for securing biological-science job offers.

Genome-resolved metagenomics, biogeochemistry, modelling and culture-based analysis reveal that marine bacteria consume H₂ to support growth.

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

Femtosecond laser microdissection enables transcriptomic analyses of single neurons based on their phenotype.

To study the dynamic 3D structure of specific loci, the authors combine a computer modeling scheme based on polymer physics with experimental validation. Their results indicate that chromatin dynamics are sufficiently fast to sample all possible locus conformations within minutes, generating wide dynamic variability within single cells.

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.

Reinforcement learning models of human behavior are limited in explaining the capacity for generalization. Here, the authors propose an efficient coding principle for reinforcement learning, whereby agents use compact representations, enabling human-like generalization.

Yeasts are exposed to oxidative stress during routine metabolism, bioproduction, and interactions with other organisms. Here, the authors use a machine learning classifier to identify genes that are predictive of resistance to oxidative stress across diverse yeast species.

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 Bayesian theory of mind model is shown to infer and quantify the mental state and judgements of humans in decision-making scenarios. The model is a key step towards enabling machines to ‘intuit’ human thoughts and desires.

Primary open-angle glaucoma (POAG) is highly heritable, yet not well understood from a genetic perspective. Here, the authors perform a meta-analysis of genome-wide association studies in 34,179 POAG cases, identifying 44 previously unreported risk loci and mapping effects across multiple ethnicities.

Is the incompleteness of the fossil record any reason to exclude the information that it contains? Professor Chris Paul argues that stratigraphic data is being treated inconsistently compared to other forms of data.

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.

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.

Direct sequencing of RNA molecules in real time using nanopores allows for the detection of splice variants and hold promises for profiling RNA modifications.

Safely opening university campuses has been a major challenge during the COVID-19 pandemic. Here, the authors describe a program of public health measures employed at a university in the United States which, combined with other non-pharmaceutical interventions, allowed the university to stay open in fall 2020 with limited evidence of transmission.

Through an analysis of global differences in human exposure to greenspace, a new study identifies a contrasting pattern of greenspace exposure between Global South and North cities and finds seasonal variations in greenspace exposure inequality.

Climate change and land use change may have independent or interactive effects on species’ distributions. Here, the authors show that changes in bird, lepidopteran and plant ranges across Great Britain are often explained by individual or additive effects of land conversion and temperature change.

Analysing >1,700 inventory plots from the Amazon Tree Diversity Network, the authors show that the majority of Amazon tree species can occupy floodplains and that patterns of species turnover are closely linked to regional flood patterns.

Granule cells constitute half of the cells in the brain, yet their activity during behavior is largely uncharacterized. The authors report that granule cells encode multisensory representations that evolve with learning into a predictive motor signal. This activity may help the cerebellum implement a forward model for action.

Excitatory neurons in the neocortex exhibit considerable morphological diversity, yet their organizational principles remain a subject of ongoing research. Here, the authors use unsupervised learning to show that most excitatory neuron morphologies in the mouse visual cortex form a continuum, with notable exceptions in deeper layers.

An integrated analysis of de novo and inherited coding variants in 42,607 individuals with autism spectrum disorder identifies 60 risk genes of which five have not previously been associated with neurodevelopmental disorders.

Sexual dimorphism in genetic vulnerability to schizophrenia, systemic lupus erythematosus and Sjögren’s syndrome is linked to differential protein abundance from alleles of complement component 4.

A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

Individuals over eighty years of age are less likely to mount a good immune response against SARS-CoV-2 (measured by neutralization titres) after the first dose of the BNT162b2 mRNA vaccine, but achieve good neutralization after the second dose.

Ley and colleagues show that negative selection only partially explains the difference between CD4⁺ T cell responses to self and foreign peptides and that PD-1 and CD73 synergistically limit the CD4⁺ T cell responses to self.

Gilean McVean and colleagues report the results of a large-scale clinical genome sequencing project spanning a broad spectrum of disorders. They identify factors influencing successful genetic diagnosis and highlight the challenges of interpreting findings for genetically heterogeneous disorders.

A trans-ancestry genome-wide association study of serum urate levels identifies 183 loci influencing this trait. Enrichment analyses, fine-mapping and colocalization with gene expression in 47 tissues implicate the kidney and liver as key target organs and prioritize potential causal genes.

The basement membrane stiffness is shown to be a more dominant determinant than pore size in regulating cancer cell invasion, metastasis formation and patient survival. This stiffness is now known to be affected by the ratio of netrin-4 to laminin, with more netrin-4 leading to softer basement membranes.

Systemic lupus erythematosus (SLE) is associated with altered B cell responses but the underlying aetiology is still unclear. Here the authors show that a CD11c^hiT-bet⁺ B cell subset with a unique phenotype and transcriptome is increased in patients with SLE, can be expanded by IL-21, and may contribute to autoimmune responses in SLE.

Mutations in the Protein Phosphatase PPM1D are oncogenic in certain cancers including diffuse intrinsic pontine glioma (DIPG). Here, the authors show that PPM1D mutations in DIPG induce the silencing of the nicotinic acid phosphoribosyltransferase gene and display synthetic lethality with nicotinamide phosphoribosyltransferase inhibitors.

Repeated vaccination is needed to maintain high levels of SARS-CoV-2 immunity in vulnerable populations, but there is concern that it could lead to immune exhaustion. Here, the authors assess the evidence for immune exhaustion following multiple SARS-CoV-2 vaccination three vulnerable population cohorts in Canada.

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.

Compressed Perturb-seq incorporates compressed sensing to genetic screening for scalable discovery of genetic interactions.

An extensive global transcriptomics analysis of in vivo responses to 86 cytokines across more than 17 immune cell types reveals enormous complexity of cellular responses to cytokines, providing the basis of the Immune Dictionary and its companion software Immune Response Enrichment Analysis.