{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T20:44:45Z","timestamp":1769633085293,"version":"3.49.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"1","funder":[{"name":"National Institute of Environmental Health Sciences, Division of Translational Toxicology, Division of Intramural Research"},{"name":"Spatiotemporal Exposures and Toxicology Group","award":["ZIA ES103368"],"award-info":[{"award-number":["ZIA ES103368"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Estimating a toxic reference point using tools like the benchmark dose (BMD) is a critical step in setting policy to regulate pollution and ensure safe environments. Toxicity can be measured for different endpoints, including changes in gene expression and histopathology for various tissues, and is typically explored one gene or tissue at a time in a univariate setting that ignores correlation. In this work, we develop a multivariate estimation procedure to estimate the BMD for specified gene sets. Our approach extends the foundational univariate approach by accounting for correlation in a statistically principled way.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We illustrate the method using data from a 5-day rat study and Hallmark gene sets and compare to existing BMD results computed by the EPA for both gene sets and apical histopathology endpoints. In contrast to previous ad-hoc methods, our principled approach provides the needed extension to bring the foundational univariate method into the multivariate world of transcriptomics. In addition to use in a regulatory setting, our method can provide hypothesis generation when gene sets correspond to mechanistic pathways.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>BS-BMD is implemented in R and C++ and available at https:\/\/github.com\/NIEHS\/BS-BMD.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btaf008","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T16:48:23Z","timestamp":1736441303000},"source":"Crossref","is-referenced-by-count":1,"title":["Bayesian gene set benchmark dose estimation for \u201comic\u201d responses"],"prefix":"10.1093","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4387-0271","authenticated-orcid":false,"given":"Daniel","family":"Zilber","sequence":"first","affiliation":[{"name":"Division of Intramural Research, Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences , Research Triangle Park, NC 27709,","place":["United States"]},{"name":"Division of Translational Toxicology, Predictive Toxicology Branch, National Institute of Environmental Health Sciences , Durham, NC 27713,","place":["United States"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9508-9623","authenticated-orcid":false,"given":"Kyle P","family":"Messier","sequence":"additional","affiliation":[{"name":"Division of Intramural Research, Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences , Research Triangle Park, NC 27709,","place":["United States"]},{"name":"Division of Translational Toxicology, Predictive Toxicology Branch, National Institute of Environmental Health Sciences , Durham, NC 27713,","place":["United States"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8447-7871","authenticated-orcid":false,"given":"John","family":"House","sequence":"additional","affiliation":[{"name":"Division of Intramural Research, Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences , Research Triangle Park, NC 27709,","place":["United States"]}]},{"given":"Fred","family":"Parham","sequence":"additional","affiliation":[{"name":"Division of Translational Toxicology, Predictive Toxicology Branch, National Institute of Environmental Health Sciences , Durham, NC 27713,","place":["United States"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6294-3069","authenticated-orcid":false,"given":"Scott S","family":"Auerbach","sequence":"additional","affiliation":[{"name":"Division of Translational Toxicology, Predictive Toxicology Branch, National Institute of Environmental Health Sciences , Durham, NC 27713,","place":["United States"]}]},{"given":"Matthew 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