{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T18:31:48Z","timestamp":1721673108740},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"23","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Functional relationship networks, which summarize the probability of co-functionality between any two genes in the genome, could complement the reductionist focus of modern biology for understanding diverse biological processes in an organism. One major limitation of the current networks is that they are static, while one might expect functional relationships to consistently reprogram during the differentiation of a cell lineage. To address this potential limitation, we developed a novel algorithm that leverages both differentiation stage-specific expression data and large-scale heterogeneous functional genomic data to model such dynamic changes. We then applied this algorithm to the time-course RNA-Seq data we collected for ex vivo human erythroid cell differentiation.<\/jats:p>\n               <jats:p>Results: Through computational cross-validation and literature validation, we show that the resulting networks correctly predict the (de)-activated functional connections between genes during erythropoiesis. We identified known critical genes, such as HBD and GATA1, and functional connections during erythropoiesis using these dynamic networks, while the traditional static network was not able to provide such information. Furthermore, by comparing the static and the dynamic networks, we identified novel genes (such as OSBP2 and PDZK1IP1) that are potential drivers of erythroid cell differentiation. This novel method of modeling dynamic networks is applicable to other differentiation processes where time-course genome-scale expression data are available, and should assist in generating greater understanding of the functional dynamics at play across the genome during development.<\/jats:p>\n               <jats:p>Availability and implementation: The network described in this article is available at http:\/\/guanlab.ccmb.med.umich.edu\/stageSpecificNetwork.<\/jats:p>\n               <jats:p>Contact: \u00a0gyuanfan@umich.edu or engel@umich.edu<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btu542","type":"journal-article","created":{"date-parts":[[2014,8,13]],"date-time":"2014-08-13T13:59:18Z","timestamp":1407938358000},"page":"3325-3333","source":"Crossref","is-referenced-by-count":11,"title":["Modeling dynamic functional relationship networks and application to <i>ex vivo<\/i> human erythroid differentiation"],"prefix":"10.1093","volume":"30","author":[{"given":"Fan","family":"Zhu","sequence":"first","affiliation":[{"name":"1 Department of Computational Medicine and Bioinformatics, 2Department of Cell and Developmental Biology, 3Department of Internal Medicine and 4Department of Computer Science and Engineering, University of Michigan, MI48109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lihong","family":"Shi","sequence":"additional","affiliation":[{"name":"1 Department of Computational Medicine and Bioinformatics, 2Department of Cell and Developmental Biology, 3Department of Internal Medicine and 4Department of Computer Science and Engineering, University of Michigan, MI48109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongdong","family":"Li","sequence":"additional","affiliation":[{"name":"1 Department of Computational Medicine and Bioinformatics, 2Department of Cell and Developmental Biology, 3Department of Internal Medicine and 4Department of Computer Science and Engineering, University of Michigan, MI48109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ridvan","family":"Eksi","sequence":"additional","affiliation":[{"name":"1 Department of Computational Medicine and Bioinformatics, 2Department of Cell and Developmental Biology, 3Department of Internal Medicine and 4Department of Computer Science and Engineering, University of Michigan, MI48109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James Douglas","family":"Engel","sequence":"additional","affiliation":[{"name":"1 Department of Computational Medicine and Bioinformatics, 2Department of Cell and Developmental Biology, 3Department of Internal Medicine and 4Department of Computer Science and Engineering, University of Michigan, MI48109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanfang","family":"Guan","sequence":"additional","affiliation":[{"name":"1 Department of Computational Medicine and Bioinformatics, 2Department of Cell and Developmental Biology, 3Department of Internal Medicine and 4Department of Computer Science and Engineering, University of Michigan, MI48109, USA"},{"name":"1 Department of Computational Medicine and Bioinformatics, 2Department of Cell and Developmental Biology, 3Department of Internal Medicine and 4Department of Computer Science and Engineering, University of Michigan, MI48109, USA"},{"name":"1 Department of Computational Medicine and Bioinformatics, 2Department of Cell and Developmental Biology, 3Department of Internal Medicine and 4Department of Computer Science and Engineering, University of Michigan, MI48109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2014,8,12]]},"reference":[{"key":"2023012712023242600_btu542-B1","doi-asserted-by":"crossref","first-page":"D418","DOI":"10.1093\/nar\/gki051","article-title":"The biomolecular interaction network database and related tools 2005 update","volume":"33","author":"Alfarano","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"2023012712023242600_btu542-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":"2023012712023242600_btu542-B3","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: tool for the unification of biology","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat. 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