Articles in 2022

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.

DNA 5-hydroxymethylcytosine (5hmC) is mapped in mouse preimplantation embryos, postimplantation epiblasts, primordial germ cells (PGCs) and gametes. Nlrp14 maternal depletion perturbs DNA-replication-coupled passive demethylation and impairs 5hmC deposition.

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.

Previous genome-wide association studies of coronary artery disease (CAD) have discovered multiple susceptibility loci but have largely failed to uncover causal genes. A new study identifies hundreds of likely causal genes underlying the genetic risk for CAD.

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.

Large-scale genotyping and phenotyping efforts, including biobanks, have revolutionized our understanding of the genetic architecture of human traits and diseases. Years of ever-larger genome-wide association studies (GWAS) have produced a catalog of genetic variants that contribute to complex traits. A corollary of this research has been the development of personalized polygenic scores (PGS) or polygenic risk scores (PRS).