{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T05:28:36Z","timestamp":1781674116530,"version":"3.54.5"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T00:00:00Z","timestamp":1738108800000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Central Universities of China Pharmaceutical University","award":["2632023FY04"],"award-info":[{"award-number":["2632023FY04"]}]},{"DOI":"10.13039\/501100004921","name":"Shanghai Jiao Tong University","doi-asserted-by":"publisher","award":["YG2023QNA28"],"award-info":[{"award-number":["YG2023QNA28"]}],"id":[{"id":"10.13039\/501100004921","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82404380"],"award-info":[{"award-number":["82404380"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["12222111"],"award-info":[{"award-number":["12222111"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["12331009"],"award-info":[{"award-number":["12331009"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012456","name":"National Social Science Foundation of China","doi-asserted-by":"publisher","award":["24BTJ060"],"award-info":[{"award-number":["24BTJ060"]}],"id":[{"id":"10.13039\/501100012456","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Numerous microbiome studies have revealed significant associations between the microbiome and human health and disease. These findings have motivated researchers to explore the causal role of the microbiome in human complex traits and diseases. However, the complexities of microbiome data pose challenges for statistical analysis and interpretation of causal effects.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We introduced a novel statistical framework, CRAmed, for inferring the mediating role of the microbiome between treatment and outcome. CRAmed improved the interpretability of the mediation analysis by decomposing the natural indirect effect into two parts, corresponding to the presence\u2013absence and abundance of a microbe, respectively. Comprehensive simulations demonstrated the superior performance of CRAmed in Recall, precision, and F1 score, with a notable level of robustness, compared to existing mediation analysis methods. Furthermore, two real data applications illustrated the effectiveness and interpretability of CRAmed. Our research revealed that CRAmed holds promise for uncovering the mediating role of the microbiome and understanding of the factors influencing host health.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>The R package CRAmed implementing the proposed methods is available online at https:\/\/github.com\/liudoubletian\/CRAmed.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btaf038","type":"journal-article","created":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T00:17:36Z","timestamp":1738196256000},"source":"Crossref","is-referenced-by-count":2,"title":["CRAmed: a conditional randomization test for high-dimensional mediation analysis in sparse microbiome data"],"prefix":"10.1093","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4207-8651","authenticated-orcid":false,"given":"Tiantian","family":"Liu","sequence":"first","affiliation":[{"name":"Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University , Jiangsu 211198,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1910-6126","authenticated-orcid":false,"given":"Xiangnan","family":"Xu","sequence":"additional","affiliation":[{"name":"Chair of Statistics, Humboldt-Universit\u00e4t zu Berlin , Berlin 10099,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1218-4017","authenticated-orcid":false,"given":"Tao","family":"Wang","sequence":"additional","affiliation":[{"name":"SJTU-Yale Joint Center of Biostatistics and Data Science, Shanghai Jiao Tong University , Shanghai 200240,","place":["China"]},{"name":"Department of Statistics, School of Mathematical Sciences, Shanghai Jiao Tong University , Shanghai 200240,","place":["China"]},{"name":"MOE-LSC & CMA-Shanghai, Shanghai Jiao Tong University , Shanghai 200240,","place":["China"]},{"name":"MoE Key Lab of Artificial Intelligence, AI Institute, Shanghai Jiao Tong University , Shanghai 200240,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5115-751X","authenticated-orcid":false,"given":"Peirong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Statistics, School of Mathematical Sciences, Shanghai Jiao Tong University , Shanghai 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