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Genome-wide CRISPR knockout and activation screens in human lung epithelial cells with endogenous expression of the SARS-CoV-2 entry factors ACE2 and TMPRSS2 identify mucins as key host factors restricting viral infection.
Single-cell RNA sequencing and spatiotemporal analysis of the regenerating zebrafish heart identify transient proregenerative fibroblast-like cells that are derived from the epicardium and the endocardium. Wnt signalling regulates the endocardial fibroblast response.
Biallelic loss-of-function variants in FOCAD cause a syndromic form of pediatric liver disease by compromising the SKI messenger RNA surveillance pathway.
TRIM28 depletion in embryonic stem cells disconnects transcriptional condensates from super-enhancers, which is rescued by knockdown of endogenous retroviruses.
A reference-quality genome assembly of hexaploid oat variety ‘Sanfensan’ and genome assemblies of its diploid and tetraploid Avena ancestors provide insights into the evolutionary history of allohexaploid oat.
Genome-wide association meta-analysis of insomnia in 593,724 cases and 1,771,286 controls identifies 554 risk loci and implicates specific biological pathways through gene prioritization.
Genetic and functional studies implicate allele-specific regulation of OAS1 splicing and nonsense-mediated decay in COVID-19 severity. The OAS1 risk haplotype is also associated with reduced SARS-CoV-2 clearance in a clinical trial with pegIFN-λ1.
YAP upregulates TET1, which physically interacts with TEAD1/4 to demethylate DNA at YAP target genes in the liver. Loss of TET1 reverses YAP-induced chromatin and transcriptional changes and suppresses YAP-induced hepatomegaly and tumorigenesis.
Analysis of whole-exome sequencing data from 200,453 UK Biobank participants identifies loci associated with clonal hematopoiesis and highlights causal links between clonal hematopoiesis and other traits.
A modified fluctuation test applied to colorectal cancer cells shows that EGFR/BRAF inhibitor-induced persisters slowly proliferate and have an increased mutation rate. Error-prone DNA polymerases are identified as potential targets to avoid tumor recurrence following treatment with these drugs.
Genetically dissecting the Epha4–Pax3 topological boundary in mice shows that divergent CTCF binding sites (CBSs) are not essential for insulation and that chromatin loops in nonconvergently oriented CBSs can be driven by a loop interference mechanism.
An analysis of POLE and POLD1 mutations distinguishes driver mutations from passengers and explores their functionality. Driver mutations are associated with specific mutational signatures and correlate with immune checkpoint blockage response.
Pooled loss-of-function CRISPR screens in primary human T cells identify upstream regulators of IL2RA, IL-2 and CTLA4. Individual knockouts of 24 regulators of IL2RA define a central network enriched for genes associated with immune-mediated diseases.
DeepLoop is a modular Hi-C processing workflow that enables kilobase-resolution analysis of sparse data. Reanalysis of published data demonstrates that DeepLoop can identify allele-specific chromatin loops and large heterozygous structural variants.
Sei is a new framework for integrating human genetics data with a sequence-based mapping of predicted regulatory activities to elucidate mechanisms contributing to complex traits and diseases.
The DANIO-CODE consortium leverages a large-scale multiomic dataset to improve zebrafish genome annotation. They identify ~140,000 cis-regulatory elements throughout development and perform a comparison with the mouse regulatory landscape.
A single-cell transcriptomic analysis of 63 patients with colorectal cancer classifies tumor cells into two epithelial subtypes. An improved tumor classification based on epithelial subtype, microsatellite stability and fibrosis reveals differences in pathway activation and metastasis.
Single-cell ATAC-seq and RNA-seq profiling traces the transformation of healthy colon to precancerous adenomas to colorectal cancer (CRC). A large proportion of polyp and CRC cells show a stem-like phenotype.