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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.
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.
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.
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.
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.
Sort-assisted single-cell chromatin immunocleavage (sortChIC) combines single-cell histone modification profiling with fluorescence-activated cell sorting (FACS), enabling the study of rare cell populations. H3K4me1/H3K4me3, H3K9me3 and H3K27me3 profiling of blood suggest a model of lineage-shared repressive and cell type-specific active chromatin.
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.
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.
Genome-wide association analyses, functionally informed fine-mapping and complementary gene prioritization approaches identify new risk loci and candidate effector genes for CAD.
Pan-genome and pan-3D genome analyses of the Gossypium genus reveal evolutionary relationships among transposon-driven genome expansion and chromatin topology innovation and regulatory variations for cotton fiber development.
Live-cell imaging shows that interactions within topologically associating domains are transient and frequent throughout the cell cycle. Convergent CTCF sites regulate the frequency and duration of interactions, which last a few minutes on average.
Micro-C and nascent transcript profiling in mouse embryonic stem cells shows that enhancer–promoter interactions are robust to acute depletion of CTCF, cohesin, WAPL or YY1. Live-cell, single-molecule imaging shows that cohesin depletion reduces transcription factor binding to chromatin.
Cross-trait meta-analysis on 12 psychiatric disorders identifies the genetic overlap between pairs of disorders and highlights the challenges of cross-trait genetic research.
Comprehensive genomic profiling of human H3K27M mutant diffuse midline gliomas, combining single-cell RNA sequencing and ATAC sequencing with bulk ChIP sequencing and other data, proposes distinct oligodendrocyte populations as potential cells of origin.
SD6, which encodes a bHLH transcription factor, along with another bHLH factor ICE2, antagonistically controls rice seed dormancy by regulating ABA catabolism and biosynthesis genes in a temperature-dependent manner.
Single-cell RNA-seq and ATAC-seq, combined with spatial transcriptomics, identify age- and location-related cellular dynamics of diffuse midline gliomas, such as variable oligodendrocyte precursor-like tumor stem cell populations and increased mesenchymal states with age.
CRISPR-Select is a quantitative assay for the functional impact of genetic variants, including pathogenicity, drug response, oncogenicity, cell motility and other cell states.