High-coverage whole-genome sequencing of the expanded 1000 Genomes Project cohort including 602 trios

Cell, Journal Year: 2022, Volume and Issue: 185(18), P. 3426 - 3440.e19

Published: Sept. 1, 2022

The 1000 Genomes Project (1kGP) is the largest fully open resource of whole-genome sequencing (WGS) data consented for public distribution without access or use restrictions. final, phase 3 release 1kGP included 2,504 unrelated samples from 26 populations and was based primarily on low-coverage WGS. Here, we present a high-coverage 3,202-sample WGS resource, which now includes 602 complete trios, sequenced to depth 30X using Illumina. We performed single-nucleotide variant (SNV) short insertion deletion (INDEL) discovery generated comprehensive set structural variants (SVs) by integrating multiple analytic methods through machine learning model. show gains in sensitivity precision calls compared 3, especially among rare SNVs as well INDELs SVs spanning frequency spectrum. also an improved reference imputation panel, making discovered here accessible association studies.

Language: Английский

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Multimodal biomedical AI

Nature Medicine, Journal Year: 2022, Volume and Issue: 28(9), P. 1773 - 1784

Published: Sept. 1, 2022

Language: Английский

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A genomic mutational constraint map using variation in 76,156 human genomes

Nature, Journal Year: 2023, Volume and Issue: 625(7993), P. 92 - 100

Published: Dec. 6, 2023

Language: Английский

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A saturated map of common genetic variants associated with human height

Nature, Journal Year: 2022, Volume and Issue: 610(7933), P. 704 - 712

Published: Oct. 12, 2022

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes

Language: Английский

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15 years of GWAS discovery: Realizing the promise

The American Journal of Human Genetics, Journal Year: 2023, Volume and Issue: 110(2), P. 179 - 194

Published: Jan. 11, 2023

Language: Английский

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A genome-wide mutational constraint map quantified from variation in 76,156 human genomes

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: March 21, 2022

Abstract The depletion of disruptive variation caused by purifying natural selection (constraint) has been widely used to investigate protein-coding genes underlying human disorders, but attempts assess constraint for non-protein-coding regions have proven more difficult. Here we aggregate, process, and release a dataset 76,156 genomes from the Genome Aggregation Database (gnomAD), largest public open-access genome reference dataset, use this build mutational map whole genome. We present refined model that incorporates local sequence context regional genomic features detect depletions across As expected, proteincoding sequences overall are under stronger than non-coding regions. Within genome, constrained enriched known regulatory elements variants implicated in complex diseases traits, facilitating triangulation biological annotation, disease association, DNA analysis. More tend regulate genes, while captures additional functional information underrecognized gene metrics. demonstrate genome-wide provides an effective approach characterizing improving identification interpretation genetic variation.

Language: Английский

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The UCSC Genome Browser database: 2024 update

Nucleic Acids Research, Journal Year: 2023, Volume and Issue: 52(D1), P. D1082 - D1088

Published: Nov. 11, 2023

The UCSC Genome Browser (https://genome.ucsc.edu) is a web-based genomic visualization and analysis tool that serves data to over 7,000 distinct users per day worldwide. It provides annotation on thousands of genome assemblies, ranging from human SARS-CoV2. This year, we have introduced new the Human Pangenome Reference Consortium viral genomes including We added 1,200 our GenArk system, increasing overall diversity representation. support for nine user-contributed track hubs public hub system. Additionally, released 29 tracks 11 mouse genome. Collectively, these features expand both breadth depth knowledge share publicly with

Language: Английский

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Genomic data in the All of Us Research Program

Nature, Journal Year: 2024, Volume and Issue: 627(8003), P. 340 - 346

Published: Feb. 19, 2024

Abstract Comprehensively mapping the genetic basis of human disease across diverse individuals is a long-standing goal for field genetics 1–4 . The All Us Research Program longitudinal cohort study aiming to enrol group at least one million USA accelerate biomedical research and improve health 5,6 Here we describe programme’s genomics data release 245,388 clinical-grade genome sequences. This resource unique in its diversity as 77% participants are from communities that historically under-represented 46% racial ethnic minorities. identified more than 1 billion variants, including 275 previously unreported 3.9 which had coding consequences. Leveraging linkage between genomic electronic record, evaluated 3,724 variants associated with 117 diseases found high replication rates both European ancestry African ancestry. Summary-level publicly available, individual-level can be accessed by researchers through Researcher Workbench using passport model median time initial researcher registration access 29 hours. We anticipate this dataset will advance promise medicine all.

Language: Английский

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Large-scale plasma proteomics comparisons through genetics and disease associations

Nature, Journal Year: 2023, Volume and Issue: 622(7982), P. 348 - 358

Published: Oct. 4, 2023

High-throughput proteomics platforms measuring thousands of proteins in plasma combined with genomic and phenotypic information have the power to bridge gap between genome diseases. Here we performed association studies Olink Explore 3072 data generated by UK Biobank Pharma Proteomics Project

Language: Английский

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Trials and Tribulations of MicroRNA Therapeutics

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1469 - 1469

Published: Jan. 25, 2024

The discovery of the link between microRNAs (miRNAs) and a myriad human diseases, particularly various cancer types, has generated significant interest in exploring their potential as novel class drugs. This led to substantial investments interdisciplinary research fields such biology, chemistry, medical science for development miRNA-based therapies. Furthermore, recent global success SARS-CoV-2 mRNA vaccines against COVID-19 pandemic further revitalized RNA-based immunotherapies, including approaches treatment. Consequently, RNA therapeutics have emerged highly adaptable modular options therapy. Moreover, advancements chemistry delivery methods been pivotal shaping landscape immunotherapy, approaches. biotechnology pharmaceutical industry witnessed resurgence incorporating immunotherapies miRNA into programs. Despite progress preclinical research, field remains its early stages, with only few progressing clinical development, none reaching phase III trials or being approved by US Food Drug Administration (FDA), several facing termination due toxicity issues. These setbacks highlight existing challenges that must be addressed broad application therapeutics. Key include establishing sensitivity, specificity, selectivity towards intended targets, mitigating immunogenic reactions off-target effects, developing enhanced targeted delivery, determining optimal dosing therapeutic efficacy while minimizing side effects. Additionally, limited understanding precise functions miRNAs limits utilization. viable treatment, they technically economically feasible widespread adoption As result, thorough risk evaluation is crucial minimize prevent overdosing, address other Nevertheless, diseases evident, future investigations are essential determine applicability settings.

Language: Английский

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