{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:35:00Z","timestamp":1772138100118,"version":"3.50.1"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2019,11,8]],"date-time":"2019-11-08T00:00:00Z","timestamp":1573171200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01GM109215"],"award-info":[{"award-number":["R01GM109215"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01AR042742"],"award-info":[{"award-number":["R01AR042742"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Gene set enrichment analysis has been shown to be effective in identifying relevant biological pathways underlying complex diseases. Existing approaches lack the ability to quantify the enrichment levels accurately, hence preventing the enrichment information to be further utilized in both upstream and downstream analyses. A modernized and rigorous approach for gene set enrichment analysis that emphasizes both hypothesis testing and enrichment estimation is much needed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We propose a novel computational method, Bayesian Analysis of Gene Set Enrichment (BAGSE), for gene set enrichment analysis. BAGSE is built on a Bayesian hierarchical model and fully accounts for the uncertainty embedded in the association evidence of individual genes. We adopt an empirical Bayes inference framework to fit the proposed hierarchical model by implementing an efficient EM algorithm. Through simulation studies, we illustrate that BAGSE yields accurate enrichment quantification while achieving similar power as the state-of-the-art methods. Further simulation studies show that BAGSE can effectively utilize the enrichment information to improve the power in gene discovery. Finally, we demonstrate the application of BAGSE in analyzing real data from a differential expression experiment and a transcriptome-wide association study. Our results indicate that the proposed statistical framework is effective in aiding the discovery of potentially causal pathways and gene networks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>BAGSE is implemented using the C++ programing language and is freely available from https:\/\/github.com\/xqwen\/bagse\/. Simulated and real data used in this paper are also available at the Github repository for reproducibility purposes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Supplementary information<\/jats:title>\n                    <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btz831","type":"journal-article","created":{"date-parts":[[2019,11,6]],"date-time":"2019-11-06T15:11:00Z","timestamp":1573053060000},"page":"1689-1695","source":"Crossref","is-referenced-by-count":10,"title":["BAGSE: a Bayesian hierarchical model approach for gene set enrichment analysis"],"prefix":"10.1093","volume":"36","author":[{"given":"Abhay","family":"Hukku","sequence":"first","affiliation":[{"name":"Department of Biostatistics, University of Michigan , Ann Arbor, MI 48109, USA"}]},{"given":"Corbin","family":"Quick","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Michigan , Ann Arbor, MI 48109, USA"}]},{"given":"Francesca","family":"Luca","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine and Genetics, Wayne State University , Detroit, MI 48201, USA"}]},{"given":"Roger","family":"Pique-Regi","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine and Genetics, Wayne State University , Detroit, MI 48201, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8990-2737","authenticated-orcid":false,"given":"Xiaoquan","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Michigan , Ann Arbor, MI 48109, USA"}]}],"member":"286","published-online":{"date-parts":[[2019,11,8]]},"reference":[{"key":"2023060911503607100_btz831-B1","first-page":"045260","article-title":"MetaXcan: summary statistics based gene-level association method infers accurate prediXcan results","author":"Barbeira","year":"2016","journal-title":"bioRxiv"},{"key":"2023060911503607100_btz831-B2","doi-asserted-by":"crossref","first-page":"e1003770","DOI":"10.1371\/journal.pgen.1003770","article-title":"Integrated enrichment analysis of variants and pathways in genome-wide association studies indicates central role for il-2 signaling genes in type 1 diabetes, and cytokine signaling genes in Crohn\u2019s disease","volume":"9","author":"Carbonetto","year":"2013","journal-title":"PLoS Genet"},{"key":"2023060911503607100_btz831-B3","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.ygeno.2016.01.004","article-title":"COPD subtypes identified by network-based clustering of blood gene expression","volume":"107","author":"Chang","year":"2016","journal-title":"Genomics"},{"key":"2023060911503607100_btz831-B4","volume-title":"Large-Scale Inference: Empirical Bayes Methods for Estimation, Testing, and Prediction.","author":"Efron","year":"2012"},{"key":"2023060911503607100_btz831-B5","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.jpsychires.2015.09.017","article-title":"Activated immune\u2013inflammatory pathways are associated with long-standing depressive symptoms: evidence from gene-set enrichment analyses in the Young Finns Study","volume":"71","author":"Elovainio","year":"2015","journal-title":"J. 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