{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:13:30Z","timestamp":1787318010833,"version":"build-2736575974"},"posted":{"date-parts":[[2025,2,19]]},"group-title":"Bioinformatics","reference-count":41,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T00:00:00Z","timestamp":1739923200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["P30-CA008748"],"award-info":[{"award-number":["P30-CA008748"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Correlating time-dependent patient characteristics and matched microbiome samples can identify biomarkers in longitudinal microbiome studies. Existing approaches typically repeat a pre-specified modeling approach for all taxonomic features, followed by a multiple testing adjustment step for false discovery rate (FDR) control. In this work, we develop an alternative strategy of using log-ratio penalized generalized estimating equations, which directly models the longitudinal patient characteristic of interest as the outcome variable and treats microbial features as high-dimensional compositional covariates. A cross validation procedure is developed for variable selection and model selection among different working correlation structures. In extensive simulations, the proposed method achieved superior sensitivity over the state-of-the-art methods with robustly controlled FDR. In the analyses of correlating longitudinal dietary intake, bloodstream infection status, and microbial features from matched samples of cancer patients, the proposed method effectively identified gut health indicators and clinically relevant microbial markers, showing robust utilities in real-world applications. The method is implemented under the open-source R package\n                  <jats:monospace>FLORAL<\/jats:monospace>\n                  , which is available at (\n                  <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/vdblab.github.io\/FLORAL\/\">https:\/\/vdblab.github.io\/FLORAL\/<\/jats:ext-link>\n                  ).\n                <\/jats:p>","DOI":"10.1101\/2025.02.17.638558","type":"posted-content","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T04:55:23Z","timestamp":1739940923000},"source":"Crossref","is-referenced-by-count":1,"title":["Correlating High-dimensional longitudinal microbial features with time-varying outcomes with FLORAL"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7888-1715","authenticated-orcid":false,"given":"Teng","family":"Fei","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Donovan","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center"},{"name":"Department of Biostatistics, Harvard T.H. Chan School of Public Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1612-5644","authenticated-orcid":false,"given":"Tyler","family":"Funnell","sequence":"additional","affiliation":[{"name":"Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirae","family":"Baichoo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas R.","family":"Waters","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Paredes","sequence":"additional","affiliation":[{"name":"Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anqi","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Medicine, Memorial Sloan Kettering Cancer Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Castro","sequence":"additional","affiliation":[{"name":"Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Haber","sequence":"additional","affiliation":[{"name":"Molecular Microbiology Facility, Department of Immunology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Gradissimo","sequence":"additional","affiliation":[{"name":"Molecular Microbiology Facility, Department of Immunology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep S.","family":"Raj","sequence":"additional","affiliation":[{"name":"Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9321-702X","authenticated-orcid":false,"given":"Alexander M.","family":"Lesokhin","sequence":"additional","affiliation":[{"name":"Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center"},{"name":"Department of Medicine, Weill Cornell Medical College"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8419-1091","authenticated-orcid":false,"given":"Urvi A.","family":"Shah","sequence":"additional","affiliation":[{"name":"Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center"},{"name":"Department of Medicine, Weill Cornell Medical College"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel R. M.","family":"van den Brink","sequence":"additional","affiliation":[{"name":"Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center"},{"name":"Hematologic Malignancies Research Institute, City of Hope National Medical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4029-7625","authenticated-orcid":false,"given":"Jonathan U.","family":"Peled","sequence":"additional","affiliation":[{"name":"Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center"},{"name":"Department of Medicine, Weill Cornell Medical College"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041110295164000_2025.02.17.638558v2.1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa068"},{"key":"2026041110295164000_2025.02.17.638558v2.2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis580"},{"key":"2026041110295164000_2025.02.17.638558v2.3","doi-asserted-by":"crossref","unstructured":"Dai, A. et al. 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