The GTEx Consortium atlas of genetic regulatory effects across human tissues

Science, Journal Year: 2020, Volume and Issue: 369(6509), P. 1318 - 1330

Published: Sept. 10, 2020

The Genotype-Tissue Expression (GTEx) project dissects how genetic variation affects gene expression and splicing.

Language: Английский

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RCSB Protein Data Bank: powerful new tools for exploring 3D structures of biological macromolecules for basic and applied research and education in fundamental biology, biomedicine, biotechnology, bioengineering and energy sciences

Nucleic Acids Research, Journal Year: 2020, Volume and Issue: 49(D1), P. D437 - D451

Published: Nov. 17, 2020

Abstract The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), the US data center global PDB archive and a founding member of Worldwide partnership, serves tens thousands depositors in Americas Oceania makes 3D macromolecular structure available at no charge without restrictions to millions RCSB.org users around world, including >660 000 educators, students members curious public using PDB101.RCSB.org. include structural biologists crystallography, nuclear magnetic resonance spectroscopy, electron microscopy micro-electron diffraction. consumers accessing our web portals researchers, educators studying fundamental biology, biomedicine, biotechnology, bioengineering energy sciences. During past 2 years, research-focused RCSB portal (RCSB.org) has undergone complete redesign, enabling improved searching with full Boolean operator logic more facile access integrated >40 external biodata resources. New features resources are described detail examples that showcase recently released structures SARS-CoV-2 proteins host cell relevant understanding addressing COVID-19 pandemic.

Language: Английский

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Genome-wide association studies

Nature Reviews Methods Primers, Journal Year: 2021, Volume and Issue: 1(1)

Published: Aug. 26, 2021

Genome-wide association studies (GWAS) test hundreds of thousands genetic variants across many genomes to find those statistically associated with a specific trait or disease. This methodology has generated myriad robust associations for range traits and diseases, the number is expected grow steadily as GWAS sample sizes increase. results have applications, such gaining insight into phenotype's underlying biology, estimating its heritability, calculating correlations, making clinical risk predictions, informing drug development programmes inferring potential causal relationships between factors health outcomes. In this Primer, we provide reader an introduction GWAS, explaining their statistical basis how they are conducted, describe state-of-the art approaches discuss limitations challenges, concluding overview current future applications results. Uffelmann et al. key considerations best practices conducting genome-wide (GWAS), techniques deriving functional inferences from in understanding disease architecture. The Primer also provides information on data sharing discusses important ethical when considering populations data.

Language: Английский

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Single-cell chromatin state analysis with Signac

Nature Methods, Journal Year: 2021, Volume and Issue: 18(11), P. 1333 - 1341

Published: Nov. 1, 2021

Language: Английский

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Mapping the human genetic architecture of COVID-19

Nature, Journal Year: 2021, Volume and Issue: 600(7889), P. 472 - 477

Published: July 8, 2021

The genetic make-up of an individual contributes to the susceptibility and response viral infection. Although environmental, clinical social factors have a role in chance exposure SARS-CoV-2 severity COVID-191,2, host genetics may also be important. Identifying host-specific reveal biological mechanisms therapeutic relevance clarify causal relationships modifiable environmental risk for infection outcomes. We formed global network researchers investigate human COVID-19 severity. Here we describe results three genome-wide association meta-analyses that consist up 49,562 patients with from 46 studies across 19 countries. report 13 significant loci are associated or severe manifestations COVID-19. Several these correspond previously documented associations lung autoimmune inflammatory diseases3-7. They represent potentially actionable Mendelian randomization analyses support smoking body-mass index although not type II diabetes. identification novel was made possible by community coming together prioritize sharing data, results, resources analytical frameworks. This working model international collaboration underscores what is future discoveries emerging pandemics, indeed any complex disease.

Language: Английский

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Effective gene expression prediction from sequence by integrating long-range interactions

Nature Methods, Journal Year: 2021, Volume and Issue: 18(10), P. 1196 - 1203

Published: Oct. 1, 2021

Abstract How noncoding DNA determines gene expression in different cell types is a major unsolved problem, and critical downstream applications human genetics depend on improved solutions. Here, we report substantially prediction accuracy from sequences through the use of deep learning architecture, called Enformer, that able to integrate information long-range interactions (up 100 kb away) genome. This improvement yielded more accurate variant effect predictions for both natural genetic variants saturation mutagenesis measured by massively parallel reporter assays. Furthermore, Enformer learned predict enhancer–promoter directly sequence competitively with methods take direct experimental data as input. We expect these advances will enable effective fine-mapping disease associations provide framework interpret cis -regulatory evolution.

Language: Английский

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Exome sequencing and analysis of 454,787 UK Biobank participants

Nature, Journal Year: 2021, Volume and Issue: 599(7886), P. 628 - 634

Published: Oct. 18, 2021

Abstract A major goal in human genetics is to use natural variation understand the phenotypic consequences of altering each protein-coding gene genome. Here we used exome sequencing 1 explore protein-altering variants and their 454,787 participants UK Biobank study 2 . We identified 12 million coding variants, including around loss-of-function 1.8 deleterious missense variants. When these were tested for association with 3,994 health-related traits, found 564 genes trait associations at P ≤ 2.18 × 10 −11 Rare variant enriched loci from genome-wide studies (GWAS), but most (91%) independent common signals. discovered several risk-increasing traits related liver disease, eye disease cancer, among others, as well risk-lowering hypertension ( SLC9A3R2 ), diabetes MAP3K15 , FAM234A ) asthma SLC27A3 ). Six associated brain imaging phenotypes, two involved neural development GBE1 PLD1 Of signals available powered replication an cohort, 81% confirmed; furthermore, generally consistent across individuals European, Asian African ancestry. illustrate ability identify gene–trait associations, elucidate function pinpoint effector that underlie GWAS scale.

Language: Английский

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Atherosclerosis: Recent developments

Cell, Journal Year: 2022, Volume and Issue: 185(10), P. 1630 - 1645

Published: May 1, 2022

Atherosclerosis is an inflammatory disease of the large arteries that major cause cardiovascular (CVD) and stroke. Here, we review current understanding molecular, cellular, genetic, environmental contributions to atherosclerosis, from both individual pathway systems perspectives. We place emphasis on recent developments, some which have yielded unexpected biology, including previously unknown heterogeneity smooth muscle cells in atherosclerotic lesions, roles for senescence clonal hematopoiesis, links gut microbiome.

Language: Английский

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The impact of sex on gene expression across human tissues

Science, Journal Year: 2020, Volume and Issue: 369(6509)

Published: Sept. 10, 2020

Many complex human phenotypes exhibit sex-differentiated characteristics. However, the molecular mechanisms underlying these differences remain largely unknown. We generated a catalog of sex in gene expression and genetic regulation across 44 tissue sources surveyed by Genotype-Tissue Expression project (GTEx, v8 release). demonstrate that influences levels cellular composition samples body. A total 37% all genes sex-biased at least one tissue. identify cis quantitative trait loci (eQTLs) with effects characterize their origin. By integrating eQTLs genome-wide association study data, we 58 gene-trait associations are driven single sex. These findings provide an extensive characterization transcriptome its regulation.

Language: Английский

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The UCSC Genome Browser database: 2021 update

Nucleic Acids Research, Journal Year: 2020, Volume and Issue: 49(D1), P. D1046 - D1057

Published: Nov. 19, 2020

Abstract For more than two decades, the UCSC Genome Browser database (https://genome.ucsc.edu) has provided high-quality genomics data visualization and genome annotations to research community. As field of grows become available, new modes display are required accommodate technologies. New features released this past year include a Hi-C heatmap display, phased family trio for VCF files, various track improvements. Striving keep up-to-date, updates gene GENCODE Genes, NCBI RefSeq Ensembl Genes. tracks added human mouse genomes ENCODE registry candidate cis-regulatory elements, promoters from Eukaryotic Promoter Database, Select Matched Annotation EMBL-EBI (MANE). Within weeks learning about outbreak coronavirus, browser, with detailed annotation tracks, SARS-CoV-2 RNA reference assembly.

Language: Английский

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