{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T11:19:04Z","timestamp":1777893544613,"version":"3.51.4"},"reference-count":15,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"vor","delay-in-days":40,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Biostate AI"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Recent advances in sequencing technology enable the capture of gene expression dynamics through longitudinal study designs. However, the field lacks robust analytical tools for these high-dimensional datasets. To address this, we developed bioinformatic methods to determine baseline gene expression variability and identify temporally varying genes (TVGs). Our dynamic cut-off metric enhances detection of differentially expressed genes (DEGs), reducing false positives and negatives, while our TVG scoring system identifies genes with fluctuating expression over time. In a 21-day longitudinal RNA-seq dataset from rats, we identified 502 DEGs and 300 high-confidence TVGs, revealing that repeated blood sampling activates pathways related to bleeding, coagulation, and inflammatory responses. These findings were recapitulated in a 9-day human longitudinal RNA-seq study, which revealed similar pathway enrichments and subject-specific expression dynamics. Additional controls confirmed that these gene expression changes were not induced by handling artifacts, and score threshold analysis enabled a tunable balance between sensitivity and specificity. Our study introduces a robust analytical framework and the largest high-frequency longitudinal RNA-seq dataset of its kind, now publicly available. These resources provide valuable insights into dynamic gene regulation and offer new approaches in systems biology, pharmacogenomics, and translational medicine.<\/jats:p>","DOI":"10.1093\/bib\/bbaf527","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:52:49Z","timestamp":1760107969000},"source":"Crossref","is-referenced-by-count":2,"title":["Novel methods for temporally varying gene identification in longitudinal studies reveal bleeding and clotting pathway activation caused by blood draws"],"prefix":"10.1093","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9278-1259","authenticated-orcid":false,"given":"Wei","family":"Chen","sequence":"first","affiliation":[{"name":"Biostate AI, Inc , 7505 Fannin St, Suite 610, Houston, Texas, 77054 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Chai","sequence":"additional","affiliation":[{"name":"Biostate AI, Inc , 7505 Fannin St, Suite 610, Houston, Texas, 77054 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Jiang","sequence":"additional","affiliation":[{"name":"Biostate AI, Inc , 7505 Fannin St, Suite 610, Houston, Texas, 77054 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5633-3419","authenticated-orcid":false,"given":"Sarah","family":"McCollum","sequence":"additional","affiliation":[{"name":"Biostate AI, Inc , 7505 Fannin St, Suite 610, Houston, Texas, 77054 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyu","family":"Weng","sequence":"additional","affiliation":[{"name":"Biostate AI, Inc , 7505 Fannin St, Suite 610, Houston, Texas, 77054 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Biostate AI, Inc , 7505 Fannin St, Suite 610, Houston, Texas, 77054 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva Yiqing","family":"Miao","sequence":"additional","affiliation":[{"name":"Biostate AI, Inc , 7505 Fannin St, Suite 610, Houston, Texas, 77054 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7637-5840","authenticated-orcid":false,"given":"Bonnie","family":"Wang","sequence":"additional","affiliation":[{"name":"Biostate AI, Inc , 7505 Fannin St, Suite 610, Houston, Texas, 77054 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashwin","family":"Gopinath","sequence":"additional","affiliation":[{"name":"Biostate AI, Inc , 7505 Fannin St, Suite 610, Houston, Texas, 77054 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Biostate AI, Inc , 7505 Fannin St, Suite 610, Houston, Texas, 77054 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,10,10]]},"reference":[{"key":"2025101010524257500_ref1","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1245\/s10434-018-07107-8","article-title":"Oncotype DX(\u00ae) recurrence score as a predictor of response to neoadjuvant chemotherapy","volume":"26","author":"Pease","year":"2019","journal-title":"Ann Surg Oncol"},{"key":"2025101010524257500_ref2","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1038\/s41467-020-14975-w","article-title":"A generalizable 29-mRNA neural-network classifier for acute bacterial and viral infections","volume":"11","author":"Mayhew","year":"2020","journal-title":"Nat Commun"},{"key":"2025101010524257500_ref3","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abb1654","article-title":"Noninvasive characterization of Alzheimer's disease by circulating, cell-free messenger RNA next-generation sequencing","volume":"6","author":"Toden","year":"2020","journal-title":"Sci Adv"},{"key":"2025101010524257500_ref4","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1161\/CIRCULATIONAHA.120.050498","article-title":"Myocardial gene expression signatures in human heart failure with preserved ejection fraction","volume":"143","author":"Hahn","year":"2021","journal-title":"Circulation"},{"key":"2025101010524257500_ref5","author":"Opinionome: Can DNA sequencing get any faster and cheaper? 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