{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T02:41:32Z","timestamp":1773196892294,"version":"3.50.1"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T00:00:00Z","timestamp":1634860800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Ministry of Science and Technology [MOST","award":["106-2320-B-002-053-MY3"],"award-info":[{"award-number":["106-2320-B-002-053-MY3"]}]},{"name":"Ministry of Science and Technology [MOST","award":["MOST 107-2221-E-010-017-MY2"],"award-info":[{"award-number":["MOST 107-2221-E-010-017-MY2"]}]},{"name":"Ministry of Science and Technology [MOST","award":["MOST 109-2221-E-010-011-MY3"],"award-info":[{"award-number":["MOST 109-2221-E-010-011-MY3"]}]},{"name":"Ministry of Science and Technology [MOST","award":["MOST 109-2320-B-002-017-MY3"],"award-info":[{"award-number":["MOST 109-2320-B-002-017-MY3"]}]},{"name":"Higher Education Sprout Project","award":["NTU-109L8837A"],"award-info":[{"award-number":["NTU-109L8837A"]}]},{"name":"Higher Education Sprout Project","award":["110L8808"],"award-info":[{"award-number":["110L8808"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>The hourglass model is a popular evo-devo model depicting that the developmental constraints in the middle of a developmental process are higher, and hence the phenotypes are evolutionarily more conserved, than those that occur in early and late ontogeny stages. Although this model has been supported by studies analyzing developmental gene expression data, the evolutionary explanation and molecular mechanism behind this phenomenon are not fully understood yet. To approach this problem, Raff proposed a hypothesis and claimed that higher interconnectivity among elements in an organism during organogenesis resulted in the larger constraints at the mid-developmental stage. By employing stochastic network analysis and gene-set pathway analysis, we aim to demonstrate such changes of interconnectivity claimed in Raff\u2019s hypothesis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We first compared the changes of network randomness among developmental processes in different species by measuring the stochasticity within the biological network in each developmental stage. By tracking the network entropy along each developmental process, we found that the network stochasticity follows an anti-hourglass trajectory, and such a pattern supports Raff\u2019s hypothesis in dynamic changes of interconnections among biological modules during development. To understand which biological functions change during the transition of network stochasticity, we sketched out the pathway dynamics along the developmental stages and found that species may activate similar groups of biological processes across different stages. Moreover, higher interspecies correlations are found at the mid-developmental stages.<\/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\/btab735","type":"journal-article","created":{"date-parts":[[2021,10,19]],"date-time":"2021-10-19T13:49:41Z","timestamp":1634651381000},"page":"763-769","source":"Crossref","is-referenced-by-count":1,"title":["Phylotranscriptomic patterns of network stochasticity and pathway dynamics during embryogenesis"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8564-8524","authenticated-orcid":false,"given":"Kuei-Yueh","family":"Ko","sequence":"first","affiliation":[{"name":"Genome and Systems Biology Degree Program, National Taiwan University , Taipei 106, Taiwan"},{"name":"Computational Biology and Bioinformatics Program, Duke University , Durham, NC 27710, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7915-7814","authenticated-orcid":false,"given":"Cho-Yi","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Informatics, National Yang Ming Chiao Tung University , Taipei 112, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4876-3309","authenticated-orcid":false,"given":"Hsueh-Fen","family":"Juan","sequence":"additional","affiliation":[{"name":"Genome and Systems Biology Degree Program, National Taiwan University , Taipei 106, Taiwan"},{"name":"Department of Life Science, Graduate Institute of Biomedical Electronics and Bioinformatics, Center for Computational and Systems Biology, National Taiwan University , Taipei 106, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3386-0934","authenticated-orcid":false,"given":"Hsuan-Cheng","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Informatics, National Yang Ming Chiao Tung University , Taipei 112, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,10,22]]},"reference":[{"key":"2023020108483610100_btab735-B1","doi-asserted-by":"crossref","first-page":"156","DOI":"10.12688\/f1000research.4583.2","article-title":"An explanatory evo-devo model for the developmental hourglass","volume":"3","author":"Akhshabi","year":"2014","journal-title":"F1000Research"},{"key":"2023020108483610100_btab735-B2","doi-asserted-by":"crossref","first-page":"3039","DOI":"10.1038\/srep03039","article-title":"Cellular network entropy as the energy potential in Waddington\u2019s differentiation landscape","volume":"3","author":"Banerji","year":"2013","journal-title":"Sci. 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