{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:34:06Z","timestamp":1772138046737,"version":"3.50.1"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"23","license":[{"start":{"date-parts":[[2021,6,27]],"date-time":"2021-06-27T00:00:00Z","timestamp":1624752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000893","name":"Simons Foundation","doi-asserted-by":"publisher","award":["597491-RWC"],"award-info":[{"award-number":["597491-RWC"]}],"id":[{"id":"10.13039\/100000893","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1764421"],"award-info":[{"award-number":["1764421"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000893","name":"Simons Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000893","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,12,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>The circadian rhythm drives the oscillatory expression of thousands of genes across all tissues. The recent revolution in high-throughput transcriptomics, coupled with the significant implications of the circadian clock for human health, has sparked an interest in circadian profiling studies to discover genes under circadian control.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>We present TimeCycle: a topology-based rhythm detection method designed to identify cycling transcripts. For a given time-series, the method reconstructs the state space using time-delay embedding, a data transformation technique from dynamical systems theory. In the embedded space, Takens\u2019 theorem proves that the dynamics of a rhythmic signal will exhibit circular patterns. The degree of circularity of the embedding is calculated as a persistence score using persistent homology, an algebraic method for discerning the topological features of data. By comparing the persistence scores to a bootstrapped null distribution, cycling genes are identified. Results in both synthetic and biological data highlight TimeCycle\u2019s ability to identify cycling genes across a range of sampling schemes, number of replicates and missing data. Comparison to competing methods highlights their relative strengths, providing guidance as to the optimal choice of cycling detection method.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availabilityand implementation<\/jats:title>\n                    <jats:p>A fully documented open-source R package implementing TimeCycle is available at: https:\/\/nesscoder.github.io\/TimeCycle\/.<\/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\/btab476","type":"journal-article","created":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T15:13:34Z","timestamp":1624634014000},"page":"4405-4413","source":"Crossref","is-referenced-by-count":3,"title":["TimeCycle: topology inspired method for the detection of cycling transcripts in circadian time-series data"],"prefix":"10.1093","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3935-6667","authenticated-orcid":false,"given":"Elan","family":"Ness-Cohn","sequence":"first","affiliation":[{"name":"Department of Molecular Biosciences, Northwestern University , Evanston, IL 60208, USA"},{"name":"Biostatistics Division, Department of Preventive Medicine, Northwestern University , Chicago, IL 60611, USA"},{"name":"NSF-Simons Center for Quantitative Biology, Northwestern University , Evanston, IL 60208, USA"}]},{"given":"Rosemary","family":"Braun","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, Northwestern University , Evanston, IL 60208, USA"},{"name":"Biostatistics Division, Department of Preventive Medicine, Northwestern University , Chicago, IL 60611, USA"},{"name":"NSF-Simons Center for Quantitative Biology, Northwestern University , Evanston, IL 60208, USA"},{"name":"Department of Engineering Sciences and Applied Mathematics, Northwestern University , Evanston, IL 60208, USA"},{"name":"Department of Physics and Astronomy, Northwestern University , Evanston, IL 60208, USA"},{"name":"Northwestern Institute on Complex Systems, Northwestern University , Evanston, IL 60208, USA"}]}],"member":"286","published-online":{"date-parts":[[2021,6,27]]},"reference":[{"key":"2023061310485664600_btab476-B1","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1186\/1471-2105-8-233","article-title":"Robust regression for periodicity detection in non-uniformly sampled time-course gene expression data","volume":"8","author":"Ahdesm\u00e4ki","year":"2007","journal-title":"BMC Bioinformatics"},{"key":"2023061310485664600_btab476-B2","doi-asserted-by":"crossref","first-page":"R106","DOI":"10.1186\/gb-2010-11-10-r106","article-title":"Differential expression analysis for sequence count data","volume":"11","author":"Anders","year":"2010","journal-title":"Genome Biol"},{"key":"2023061310485664600_btab476-B3","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1162\/089976603321780317","article-title":"Laplacian eigenmaps for dimensionality reduction and data representation","volume":"15","author":"Belkin","year":"2003","journal-title":"Neural Comput"},{"key":"2023061310485664600_btab476-B4","doi-asserted-by":"crossref","first-page":"E9247","DOI":"10.1073\/pnas.1800314115","article-title":"Universal method for robust detection of circadian state from gene expression","volume":"115","author":"Braun","year":"2018","journal-title":"Proc. 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