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2356: openSESAME: a “search engine” for discovering drug-disease connections by leveraging publicly available high-throughput experimental data

OBJECTIVES/SPECIFIC AIMS: Microarray technology has produced large volumes of gene expression data profiling differences in gene expression in a vast array of conditions, much of which is publicly available. Methods to query these data for similarities in patterns of gene regulation are limited to c...

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Detalles Bibliográficos
Autores principales: Gower, Adam C., Spira, Avrum, Lenburg, Marc E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cambridge University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804422/
http://dx.doi.org/10.1017/cts.2017.71
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author Gower, Adam C.
Spira, Avrum
Lenburg, Marc E.
author_facet Gower, Adam C.
Spira, Avrum
Lenburg, Marc E.
author_sort Gower, Adam C.
collection PubMed
description OBJECTIVES/SPECIFIC AIMS: Microarray technology has produced large volumes of gene expression data profiling differences in gene expression in a vast array of conditions, much of which is publicly available. Methods to query these data for similarities in patterns of gene regulation are limited to comparisons between preannotated groups. In response, we developed openSESAME to find experiments where a set of genes is similarly coregulated without regard to experimental design. An important application of openSESAME is drug repositioning: if a pattern associated with disease is reversed by a given drug, the drug might target disease-related processes. METHODS/STUDY POPULATION: Experiments from the Gene Expression Omnibus (GEO) were normalized, signature-association (SA) scores computed for each sample, experiments assigned enrichment scores, and ANOVAs used to assign significance to experimental variables automatically extracted from GEO. SA scores were also generated for hundreds of publicly available signatures, and pairwise correlations used to create a relevance network. RESULTS/ANTICIPATED RESULTS: Using signatures of estrogen and p63, we recovered relevant experimental variables, and with the network approach, we recovered previously reported associations between disease states and/or drug treatments. DISCUSSION/SIGNIFICANCE OF IMPACT: openSESAME has the potential to illuminate “dark data” and discover novel relationships between drugs and diseases on the basis of common patterns of differential gene expression.
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spelling pubmed-68044222019-10-28 2356: openSESAME: a “search engine” for discovering drug-disease connections by leveraging publicly available high-throughput experimental data Gower, Adam C. Spira, Avrum Lenburg, Marc E. J Clin Transl Sci Biomedical Informatics/Health Informatics OBJECTIVES/SPECIFIC AIMS: Microarray technology has produced large volumes of gene expression data profiling differences in gene expression in a vast array of conditions, much of which is publicly available. Methods to query these data for similarities in patterns of gene regulation are limited to comparisons between preannotated groups. In response, we developed openSESAME to find experiments where a set of genes is similarly coregulated without regard to experimental design. An important application of openSESAME is drug repositioning: if a pattern associated with disease is reversed by a given drug, the drug might target disease-related processes. METHODS/STUDY POPULATION: Experiments from the Gene Expression Omnibus (GEO) were normalized, signature-association (SA) scores computed for each sample, experiments assigned enrichment scores, and ANOVAs used to assign significance to experimental variables automatically extracted from GEO. SA scores were also generated for hundreds of publicly available signatures, and pairwise correlations used to create a relevance network. RESULTS/ANTICIPATED RESULTS: Using signatures of estrogen and p63, we recovered relevant experimental variables, and with the network approach, we recovered previously reported associations between disease states and/or drug treatments. DISCUSSION/SIGNIFICANCE OF IMPACT: openSESAME has the potential to illuminate “dark data” and discover novel relationships between drugs and diseases on the basis of common patterns of differential gene expression. Cambridge University Press 2018-05-10 /pmc/articles/PMC6804422/ http://dx.doi.org/10.1017/cts.2017.71 Text en © The Association for Clinical and Translational Science 2018 http://creativecommons.org/licenses/by/4.0/ This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Biomedical Informatics/Health Informatics
Gower, Adam C.
Spira, Avrum
Lenburg, Marc E.
2356: openSESAME: a “search engine” for discovering drug-disease connections by leveraging publicly available high-throughput experimental data
title 2356: openSESAME: a “search engine” for discovering drug-disease connections by leveraging publicly available high-throughput experimental data
title_full 2356: openSESAME: a “search engine” for discovering drug-disease connections by leveraging publicly available high-throughput experimental data
title_fullStr 2356: openSESAME: a “search engine” for discovering drug-disease connections by leveraging publicly available high-throughput experimental data
title_full_unstemmed 2356: openSESAME: a “search engine” for discovering drug-disease connections by leveraging publicly available high-throughput experimental data
title_short 2356: openSESAME: a “search engine” for discovering drug-disease connections by leveraging publicly available high-throughput experimental data
title_sort 2356: opensesame: a “search engine” for discovering drug-disease connections by leveraging publicly available high-throughput experimental data
topic Biomedical Informatics/Health Informatics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804422/
http://dx.doi.org/10.1017/cts.2017.71
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