{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:56:21Z","timestamp":1773276981342,"version":"3.50.1"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Statistical inference of gene networks by using time-course microarray gene expression profiles is an essential step towards understanding the temporal structure of gene regulatory mechanisms. Unfortunately, most of the current studies have been limited to analysing a small number of genes because the length of time-course gene expression profiles is fairly short. One promising approach to overcome such a limitation is to infer gene networks by exploring the potential transcriptional modules which are sets of genes sharing a common function or involved in the same pathway.<\/jats:p>\n               <jats:p>Results: In this article, we present a novel approach based on the state space model to identify the transcriptional modules and module-based gene networks simultaneously. The state space model has the potential to infer large-scale gene networks, e.g. of order 103, from time-course gene expression profiles. Particularly, we succeeded in the identification of a cell cycle system by using the gene expression profiles of Saccharomyces cerevisiae in which the length of the time-course and number of genes were 24 and 4382, respectively. However, when analysing shorter time-course data, e.g. of length 10 or less, the parameter estimations of the state space model often fail due to overfitting. To extend the applicability of the state space model, we provide an approach to use the technical replicates of gene expression profiles, which are often measured in duplicate or triplicate. The use of technical replicates is important for achieving highly-efficient inferences of gene networks with short time-course data. The potential of the proposed method has been demonstrated through the time-course analysis of the gene expression profiles of human umbilical vein endothelial cells (HUVECs) undergoing growth factor deprivation-induced apoptosis.<\/jats:p>\n               <jats:p>Availability: Supplementary Information and the software (TRANS-MNET) are available at http:\/\/daweb.ism.ac.jp\/~yoshidar\/software\/ssm\/<\/jats:p>\n               <jats:p>Contact: \u00a0yoshidar@ism.ac.jp<\/jats:p>\n               <jats:p>Supplementary information: Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btm639","type":"journal-article","created":{"date-parts":[[2008,2,22]],"date-time":"2008-02-22T01:52:37Z","timestamp":1203645157000},"page":"932-942","source":"Crossref","is-referenced-by-count":76,"title":["Statistical inference of transcriptional module-based gene networks from time course gene expression profiles by using state space models"],"prefix":"10.1093","volume":"24","author":[{"given":"Osamu","family":"Hirose","sequence":"first","affiliation":[{"name":"1 Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan, 2Institute of Statistical Mathematics, Research Organization of Information and Systems, 4-6-7 Minami-Azabu, Minato-ku, Tokyo, 106-8569, Japan, 3Department of Pathology, Cambridge University, Tennis Court Road, Cambridge, CB2 1QP, UK and 4Department of Molecular Medicine and Pathology, University of Auckland, Private Bag 92019, Auckland, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryo","family":"Yoshida","sequence":"additional","affiliation":[{"name":"1 Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan, 2Institute of Statistical Mathematics, Research Organization of Information and Systems, 4-6-7 Minami-Azabu, Minato-ku, Tokyo, 106-8569, Japan, 3Department of Pathology, Cambridge University, Tennis Court Road, Cambridge, CB2 1QP, UK and 4Department of Molecular Medicine and Pathology, University of Auckland, Private Bag 92019, Auckland, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seiya","family":"Imoto","sequence":"additional","affiliation":[{"name":"1 Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan, 2Institute of Statistical Mathematics, Research Organization of Information and Systems, 4-6-7 Minami-Azabu, Minato-ku, Tokyo, 106-8569, Japan, 3Department of Pathology, Cambridge University, Tennis Court Road, Cambridge, CB2 1QP, UK and 4Department of Molecular Medicine and Pathology, University of Auckland, Private Bag 92019, Auckland, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"1 Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan, 2Institute of Statistical Mathematics, Research Organization of Information and Systems, 4-6-7 Minami-Azabu, Minato-ku, Tokyo, 106-8569, Japan, 3Department of Pathology, Cambridge University, Tennis Court Road, Cambridge, CB2 1QP, UK and 4Department of Molecular Medicine and Pathology, University of Auckland, Private Bag 92019, Auckland, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoyuki","family":"Higuchi","sequence":"additional","affiliation":[{"name":"1 Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan, 2Institute of Statistical Mathematics, Research Organization of Information and Systems, 4-6-7 Minami-Azabu, Minato-ku, Tokyo, 106-8569, Japan, 3Department of Pathology, Cambridge University, Tennis Court Road, Cambridge, CB2 1QP, UK and 4Department of Molecular Medicine and Pathology, University of Auckland, Private Bag 92019, Auckland, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. Stephen","family":"Charnock-Jones","sequence":"additional","affiliation":[{"name":"1 Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan, 2Institute of Statistical Mathematics, Research Organization of Information and Systems, 4-6-7 Minami-Azabu, Minato-ku, Tokyo, 106-8569, Japan, 3Department of Pathology, Cambridge University, Tennis Court Road, Cambridge, CB2 1QP, UK and 4Department of Molecular Medicine and Pathology, University of Auckland, Private Bag 92019, Auckland, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristin","family":"Print","sequence":"additional","affiliation":[{"name":"1 Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan, 2Institute of Statistical Mathematics, Research Organization of Information and Systems, 4-6-7 Minami-Azabu, Minato-ku, Tokyo, 106-8569, Japan, 3Department of Pathology, Cambridge University, Tennis Court Road, Cambridge, CB2 1QP, UK and 4Department of Molecular Medicine and Pathology, University of Auckland, Private Bag 92019, Auckland, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoru","family":"Miyano","sequence":"additional","affiliation":[{"name":"1 Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan, 2Institute of Statistical Mathematics, Research Organization of Information and Systems, 4-6-7 Minami-Azabu, Minato-ku, Tokyo, 106-8569, Japan, 3Department of Pathology, Cambridge University, Tennis Court Road, Cambridge, CB2 1QP, UK and 4Department of Molecular Medicine and Pathology, University of Auckland, Private Bag 92019, Auckland, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2008,2,21]]},"reference":[{"issue":"Suppl. I","key":"2023020209533412300_B1","doi-asserted-by":"crossref","first-page":"i6","DOI":"10.1136\/ard.59.suppl_1.i6","article-title":"Tumor necrosis factors receptor associated signaling molecules and their role in activation of apoptosis, JNK and NF-\u03baB","volume":"59","author":"Aggarwal","year":"2000","journal-title":"Ann. Rheum. Dis"},{"key":"2023020209533412300_B2","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1098\/rstb.2007.2129","article-title":"Understanding endothelial cell apoptosis: What can the transcriptome glycome and proteome reveal?","volume":"362","author":"Affara","year":"2007","journal-title":"Phil. Trans. Roy. Soc"},{"key":"2023020209533412300_B3","doi-asserted-by":"crossref","first-page":"2270","DOI":"10.1126\/science.1072152","article-title":"Gene expression during the life cycle of Drosophila melanogaster","volume":"298","author":"Arbeitman","year":"2002","journal-title":"Science"},{"key":"2023020209533412300_B4","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1093\/bioinformatics\/btl003","article-title":"Inference of gene regulatory networks and compound mode of action from time-course gene expression profiles","volume":"22","author":"Bansal","year":"2006","journal-title":"Bioinformatics"},{"key":"2023020209533412300_B5","first-page":"166","article-title":"Transcription-based prediction of response to IFNb using supervised computational methods","volume":"3","author":"Baranzini","year":"2005","journal-title":"PLoS Biology"},{"key":"2023020209533412300_B6","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1093\/bioinformatics\/bti014","article-title":"A Bayesian approach to reconstructing genetic regulatory networks with hidden factors","volume":"21","author":"Beal","year":"2005","journal-title":"Bioinformatics"},{"key":"2023020209533412300_B7","doi-asserted-by":"crossref","first-page":"3710","DOI":"10.1093\/bioinformatics\/bth456","article-title":"GO::TermFinder\u2013open source software for accessing Gene Ontology information and finding significantly enriched Gene Ontology terms associated with a list of genes","volume":"20","author":"Boyle","year":"2004","journal-title":"Bioinformatics"},{"issue":"1","key":"2023020209533412300_B8","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/74651","article-title":"Mechanisms of angiogenesis and arteriogenesis","volume":"6","author":"Carmeliet","year":"2000","journal-title":"Nat. Med"},{"key":"2023020209533412300_B9","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1126\/science.1081900","article-title":"Inferring genetic networks and identifying compound mode of action via expression profiling","volume":"102","author":"Gardner","year":"2003","journal-title":"Science"},{"key":"2023020209533412300_B10","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1242\/dev.126.6.1149","article-title":"VEGF is required for growth and survival in neonatal mice","volume":"126","author":"Gerver","year":"1999","journal-title":"Development"},{"key":"2023020209533412300_B11","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1074\/jbc.274.2.787","article-title":"Tumor necrosis factor-alpha-inducible IkappaBalpha proteolysis mediated by cytosolic m-calpain. A mechanism parallel to the ubiquitin-proteasome pathway for nuclear factor-kappab activation","volume":"274","author":"Han","year":"1999","journal-title":"J. Biol. Chem"},{"key":"2023020209533412300_B12","first-page":"559","article-title":"Computational strategy for discovering druggable gene networks from genome-wide RNA expression profiles","volume":"11","author":"Imoto","year":"2006","journal-title":"Pacific Symp. Biocomput"},{"key":"2023020209533412300_B13","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1096\/fj.03-0097fje","article-title":"Endothelial cells preparing to die by apoptosis initiate a program of transcriptome and glycome regulation","volume":"18","author":"Johnson","year":"2003","journal-title":"FASEB J"},{"key":"2023020209533412300_B14","doi-asserted-by":"crossref","first-page":"22382","DOI":"10.1074\/jbc.M100938200","article-title":"Inhibition of NF-kappa B activity by thalidomide through suppression of IkappaB kinase activity","volume":"276","author":"Keifer","year":"2001","journal-title":"J. Biol. Chem"},{"key":"2023020209533412300_B15","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4612-0761-0","volume-title":"Smoothness priors analysis of time series","author":"Kitagawa","year":"1996"},{"key":"2023020209533412300_B16","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1126\/science.1075090","article-title":"Transcriptional regulatory networks in Saccharomyces cerevisiae","volume":"798","author":"Lee","year":"2002","journal-title":"Science"},{"key":"2023020209533412300_B17","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1093\/bioinformatics\/btk034","article-title":"Using a state-space model with hidden variables to infer transcription factor activities","volume":"22","author":"Li","year":"2006","journal-title":"Bioinformatics"},{"key":"2023020209533412300_B18","doi-asserted-by":"crossref","first-page":"14819","DOI":"10.1073\/pnas.0604320103","article-title":"Genome-wide functional analysis of human cell-cycle regulators","volume":"103","author":"Mukherji","year":"2006","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023020209533412300_B19","doi-asserted-by":"crossref","first-page":"478","DOI":"10.4161\/cc.6.4.3859","article-title":"A probabilistic model for cell cycle distributions in synchrony experiments","volume":"6","author":"Orlando","year":"2007","journal-title":"Cell Cycle"},{"key":"2023020209533412300_B20","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1093\/bioinformatics\/bth093","article-title":"Modeling T-cell activation using gene expression profiling and state-space models","volume":"20","author":"Rangel","year":"2004","journal-title":"Bioinformatics"},{"key":"2023020209533412300_B21","doi-asserted-by":"crossref","first-page":"19368","DOI":"10.1074\/jbc.274.27.19368","article-title":"The human tumor necrosis factor (TNF) receptor-associated factor 1 gene (TRAF1) is up-regulated by cytokines of the TNF ligand family and modulates TNF-induced activation of NF-kappaB and c-Jun N-terminal kinase","volume":"274","author":"Schwenzer","year":"1999","journal-title":"J. Biol. Chem"},{"key":"2023020209533412300_B22","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1038\/ng1165","article-title":"Module networks: identifying regulatory modules and their condition-specific regulators from gene expression data","volume":"34","author":"Segal","year":"2003","journal-title":"Nat. Genet"},{"key":"2023020209533412300_B23","volume-title":"Density Estimation for Statistics and Data Analysis","author":"Silverman","year":"1986"},{"key":"2023020209533412300_B24","doi-asserted-by":"crossref","first-page":"3273","DOI":"10.1091\/mbc.9.12.3273","article-title":"Comprehensive identification of cell cycle regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization","volume":"9","author":"Spellman","year":"1998","journal-title":"Mol. Biol. Cell"},{"key":"2023020209533412300_B25","first-page":"182","article-title":"Identifying drug active pathways from gene networks estimated by gene expression data","volume":"16","author":"Tamada","year":"2005","journal-title":"Genome Inform"},{"key":"2023020209533412300_B26","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1093\/bioinformatics\/bti816","article-title":"Least absolute regression network analysis of the murine osteoblast differentiation network","volume":"22","author":"van Someran","year":"2006","journal-title":"Bioinformatics"},{"key":"2023020209533412300_B27","first-page":"581","article-title":"Modeling gene expression from microarray expression data with state-space equations","volume":"9","author":"Wu","year":"2004","journal-title":"Pacific Symp. Biocomput"},{"key":"2023020209533412300_B28","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1109\/MSP.2007.273053","article-title":"Finding module-based gene networks in time-course gene expression data with state space models","volume":"24","author":"Yamaguchi","year":"2007","journal-title":"IEEE Signal Processing Magazine"},{"key":"2023020209533412300_B29","first-page":"289","article-title":"Estimating time-dependent gene networks from time series microarray data by dynamic linear models with Markov switching","volume-title":"Proc. IEEE Comput. Syst. Bioinform. Conf","author":"Yoshida","year":"2005"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/24\/7\/932\/49048646\/bioinformatics_24_7_932.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/24\/7\/932\/49048646\/bioinformatics_24_7_932.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T11:13:13Z","timestamp":1675336393000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/24\/7\/932\/295736"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,2,21]]},"references-count":29,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2008,4,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btm639","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2008,4,1]]},"published":{"date-parts":[[2008,2,21]]}}}