Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
SPICEMIX is a computational tool that determines cell identities by analyzing intrinsic and spatial factors, enabling the identification of spatially variable metagenes and refined cell subtypes. This image shows a mixture of dried spices on a black slate, illustrating the heterogeneous cell populations in mammalian tissues.
5-hydroxymethylcytosine (5hmC) accumulates in transcribed gene regions (called ‘gene bodies’) and near enhancers, but its biological role has remained mysterious. A new study demonstrates that 5hmC serves to counteract inappropriate, spurious intragenic transcription in airway smooth muscle cells and by doing so, this DNA base functions in the prevention of chronic inflammation in the lung and an asthma-like phenotype.
A major challenge in human genetics is the prioritization of causal genes in common complex diseases. A genome-wide CRISPR screen for intracellular insulin content in a human β-cell line has now identified a new candidate gene for type 2 diabetes, demonstrating the utility of this screening approach in β-cells.
CRISPR cell and gene therapy have been designed largely with respect to a single reference human genome. A new study reveals how human genetic diversity could lead to off-target effects and presents a new tool to identify these risks.
It is well known that dietary composition affects lifespan, but whether the effects of diet are mediated through interactions with genetics is unknown. By careful tracking of genome-wide allele frequency in Drosophila, we identify hundreds of loci that affect longevity only in the context of a high-sugar diet.
The cell types of the lung enable gas exchange and protect against infection. Our spatial atlas of the human lung and airways revealed 11 new cell types and mapped their anatomical locations. In particular, we defined the gland-associated immune niche (GAIN), which is involved in fighting respiratory infections.
We profiled human DNA methylation for 987 GTEx samples across nine tissues and characterized how genetic regulation of the methylome, compared with the transcriptome, contributes to GWAS phenotypes. This resource contributes to our understanding of molecular regulatory mechanisms in human tissues and their effects on complex traits.
High-quality multimodal single-cell, bulk and spatial genomics data are prepared from low-input, frozen needle biopsy specimens collected during routine clinical procedures.
The PATAT model is used to simulate SARS-CoV-2 epidemics in low- and middle-income countries, finding that diagnostic testing rates and proportions of viruses sequenced underpin timely and accurate novel variant virus detection.
CRISPRme is an off-target nomination tool that accounts for human genetic diversity. Ancestry-dependent allele-specific off-target edits can occur with therapies currently in clinical trials, highlighting the importance of genetic variation-aware assessment.
Genome-wide association studies comprising 1,091 metabolites and 309 metabolite ratios in 8,299 individuals from the Canadian Longitudinal Study on Aging provide insights into the genetic architecture of metabolites and their role in human diseases.
A genome-wide CRISPR knockout screen in the human EndoC-βH1 pancreatic beta cell line identifies 580 regulators of intracellular insulin content. Loss of CALCOCO2 perturbs insulin granule homeostasis in pancreatic beta cells.
Multi-omics profiling of 45 human lung samples highlights 80 different cell types along the proximal to distal axis of the lung with certain cell types showing enrichment for disease-associated genes. An immune niche for IgA-expressing plasma cells within airway submucosal glands (SMG) is also identified.
SpiceMix uses latent variable modeling to infer cell identities by jointly analyzing intrinsic and spatial factors, allowing the identification of spatially variable metagenes and refined cell subtypes.
A multi-ancestry genome-wide association study meta-analysis, combined with transcriptome- and methylome-wide association analyses, identifies risk loci associated with colorectal cancer. Credible effector genes and their target tissues are also highlighted, showing that over a third probably act outside the colonic mucosa.
Smooth muscle cell-specific knockout of Tet3 in mice leads to loss of intragenic 5-hydroxymethylcytosine, accumulation of spurious transcripts and TLR7/8-mediated lung inflammation resembling asthma in human lung samples.
As part of the enhanced GTEx (eGTEx) project, 987 human samples from 9 tissue types and 424 donors are assayed using DNA methylation microarrays. Colocalization of GWAS variants, eQTLs and mQTLs shows diverse links between genetic variation, molecular phenotypes and complex traits.
An analysis of the effects of dietary stress in outbred Drosophila shows that lifespan has a polygenic architecture and is subject to environmental influence, suggesting that this context dependency is important for complex trait variation and evolution.
An integrative network map of maize (Zea mays L.) that contains genomic, transcriptomic, translatomic and proteomic networks illustrates the landscape of molecular interactions of different functional elements and potential pathway modules in maize.
MetaSTAAR enables functionally informed rare variant association analysis in biobank-scale cohorts using an efficient, sparse matrix approach for summary statistic storage.