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Integration of genetically regulated gene expression and pharmacological library provides therapeutic drug candidates.

ABSTRACT: Approaches toward new therapeutics using disease genomics, such as genome-wide association study (GWAS), are anticipated. Here, we developed Trans-Phar [integration of transcriptome-wide association study (TWAS) and pharmacological database], achieving in silico screening of compounds from a large-scale pharmacological database (L1000 Connectivity Map), which have inverse expression profiles compared with tissue-specific genetically regulated gene expression. Firstly we confirmed the statistical robustness by the application of the null GWAS data and enrichment in the true-positive drug-disease relationships by the application of UK-Biobank GWAS summary statistics in broad disease categories, then we applied the GWAS summary statistics of large-scale European meta-analysis (17 traits; naverage = 201 849) and the hospitalized COVID-19 (n = 900 687), which has urgent need for drug development. We detected potential therapeutic compounds as well as anisomycin in schizophrenia (false discovery rate (FDR)-q = 0.056) and verapamil in hospitalized COVID-19 (FDR-q = 0.068) as top-associated compounds. This approach could be effective in disease genomics-driven drug development.

SUBMITTER: Konuma T

PROVIDER: S-EPMC7928862 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Integration of genetically regulated gene expression and pharmacological library provides therapeutic drug candidates.

Konuma Takahiro T Ogawa Kotaro K Okada Yukinori Y

Human molecular genetics 20210401 3-4

Approaches toward new therapeutics using disease genomics, such as genome-wide association study (GWAS), are anticipated. Here, we developed Trans-Phar [integration of transcriptome-wide association study (TWAS) and pharmacological database], achieving in silico screening of compounds from a large-scale pharmacological database (L1000 Connectivity Map), which have inverse expression profiles compared with tissue-specific genetically regulated gene expression. Firstly we confirmed the statistical ...[more]

PMID: 33577681

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Project description:BackgroundRecent research has shown a backlash against the enthusiastic promotion of technological solutions as replacements for traditional educational content delivery. Many institutions, including the University of Virginia, have committed staff and resources to supporting state-of-the-art, showpiece educational technology projects. However, the Claude Moore Health Sciences Library has taken the approach of helping Health Sciences faculty be more comfortable using technology in incremental ways for instruction and research presentations. In July 2004, to raise awareness of self-service multimedia resources for instructional and professional development needs, the Library conducted a "Multimedia Bootcamp" for nine Health Sciences faculty and fellows.MethodsCase study.ResultsProgram stewardship by a single Library faculty member contributed to the delivery of an integrated learning experience. The amount of time required to attend the sessions and complete homework was the maximum fellows had to devote to such pursuits. The benefit of introducing technology unfamiliar to most fellows allowed program instructors to start everyone at the same baseline while not appearing to pass judgment on the technology literacy skills of faculty. The combination of wrapping the program in the trappings of a fellowship and selecting fellows who could commit to a majority of scheduled sessions yielded strong commitment from participants as evidenced by high attendance and a 100% rate of assignment completion. Response rates to follow-up evaluation requests, as well as continued use of Media Studio resources and Library expertise for projects begun or conceived during Bootcamp, bode well for the long-term success of this program.ConclusionAn incremental approach to integrating technology with current practices in instruction and presentation provided a supportive yet energizing environment for Health Sciences faculty. Keys to this program were its faculty focus, traditional hands-on instruction, unrestricted access to technology tools and support, and inclusion of criteria for evaluating when multimedia can augment pedagogical aims.

Dataset Information

Integration of genetically regulated gene expression and pharmacological library provides therapeutic drug candidates.

Publications

Integration of genetically regulated gene expression and pharmacological library provides therapeutic drug candidates.

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