{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T17:02:40Z","timestamp":1768323760540,"version":"3.49.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2020,9,15]],"date-time":"2020-09-15T00:00:00Z","timestamp":1600128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["61602352"],"award-info":[{"award-number":["61602352"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Pioneer Hundred Talents Program of Chinese Academy of Sciences"},{"name":"NSFC Excellent Young Scholars Program","award":["61722212"],"award-info":[{"award-number":["61722212"]}]},{"name":"Hong Kong Research Grants Council","award":["C1007-15G"],"award-info":[{"award-number":["C1007-15G"]}]},{"name":"Hong Kong Research Grants Council","award":["CityU 11200818"],"award-info":[{"award-number":["CityU 11200818"]}]},{"DOI":"10.13039\/100017449","name":"Hong Kong Institute for Data Science","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100017449","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Clustering analysis in a biological network is to group biological entities into functional modules, thus providing valuable insight into the understanding of complex biological systems. Existing clustering techniques make use of lower-order connectivity patterns at the level of individual biological entities and their connections, but few of them can take into account of higher-order connectivity patterns at the level of small network motifs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Here, we present a novel clustering framework, namely HiSCF, to identify functional modules based on the higher-order structure information available in a biological network. Taking advantage of higher-order Markov stochastic process, HiSCF is able to perform the clustering analysis by exploiting a variety of network motifs. When compared with several state-of-the-art clustering models, HiSCF yields the best performance for two practical clustering applications, i.e. protein complex identification and gene co-expression module detection, in terms of accuracy. The promising performance of HiSCF demonstrates that the consideration of higher-order network motifs gains new insight into the analysis of biological networks, such as the identification of overlapping protein complexes and the inference of new signaling pathways, and also reveals the rich higher-order organizational structures presented in biological networks.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>HiSCF is available at https:\/\/github.com\/allenv5\/HiSCF.<\/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\/btaa775","type":"journal-article","created":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T11:11:56Z","timestamp":1599131516000},"page":"542-550","source":"Crossref","is-referenced-by-count":110,"title":["HiSCF: leveraging higher-order structures for clustering analysis in biological networks"],"prefix":"10.1093","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1591-8549","authenticated-orcid":false,"given":"Lun","family":"Hu","sequence":"first","affiliation":[{"name":"Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Science , Urumqi 830011, China"},{"name":"School of Computer Science and Technology, Wuhan University of Technology , Wuhan 430070, China"}]},{"given":"Jun","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Computer Science and Technology, Wuhan University of Technology , Wuhan 430070, China"}]},{"given":"Xiangyu","family":"Pan","sequence":"additional","affiliation":[{"name":"School of Computer Science and Technology, Wuhan University of Technology , Wuhan 430070, China"}]},{"given":"Hong","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Electrical Engineering, City University of Hong Kong , Hong Kong 999077, China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1266-2696","authenticated-orcid":false,"given":"Zhu-Hong","family":"You","sequence":"additional","affiliation":[{"name":"Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Science , Urumqi 830011, China"}]}],"member":"286","published-online":{"date-parts":[[2020,9,15]]},"reference":[{"key":"2023051706080503400_btaa775-B1","doi-asserted-by":"crossref","first-page":"3460","DOI":"10.1105\/tpc.104.025833","article-title":"Antagonistic interaction between abscisic acid and jasmonate-ethylene signaling pathways modulates defense gene expression and disease resistance in Arabidopsis","volume":"16","author":"Anderson","year":"2004","journal-title":"Plant Cell"},{"key":"2023051706080503400_btaa775-B2","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1471-2105-4-2","article-title":"An automated method for finding molecular complexes in large protein interaction networks","volume":"4","author":"Bader","year":"2003","journal-title":"BMC Bioinformatics"},{"key":"2023051706080503400_btaa775-B3","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1126\/science.aad9029","article-title":"Higher-order organization of complex networks","volume":"353","author":"Benson","year":"2016","journal-title":"Science"},{"key":"2023051706080503400_btaa775-B4","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1137\/16M1074023","article-title":"The spacey random walk: a stochastic process for higher-order data","volume":"59","author":"Benson","year":"2017","journal-title":"SIAM Rev"},{"key":"2023051706080503400_btaa775-B5","doi-asserted-by":"crossref","first-page":"2383","DOI":"10.1105\/tpc.12.12.2383","article-title":"Activation tagging identifies a conserved myb regulator of phenylpropanoid biosynthesis","volume":"12","author":"Borevitz","year":"2000","journal-title":"Plant Cell"},{"key":"2023051706080503400_btaa775-B6","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"},{"key":"2023051706080503400_btaa775-B7","doi-asserted-by":"crossref","first-page":"D470","DOI":"10.1093\/nar\/gku1204","article-title":"The biogrid interaction database: 2015 update","volume":"43","author":"Chatr-Aryamontri","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"2023051706080503400_btaa775-B8","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/s41592-019-0509-5","article-title":"Assessment of network module identification across complex diseases","volume":"16","author":"Choobdar","year":"2019","journal-title":"Nat. Methods"},{"key":"2023051706080503400_btaa775-B9","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1074\/mcp.M600381-MCP200","article-title":"Toward a comprehensive atlas of the physical interactome of Saccharomyces cerevisiae","volume":"6","author":"Collins","year":"2007","journal-title":"Mol. Cell. Proteomics"},{"key":"2023051706080503400_btaa775-B10","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.tplants.2010.06.005","article-title":"Myb transcription factors in Arabidopsis","volume":"15","author":"Dubos","year":"2010","journal-title":"Trends Plant Sci"},{"key":"2023051706080503400_btaa775-B11","doi-asserted-by":"crossref","first-page":"3826","DOI":"10.1093\/nar\/gkh713","article-title":"Discovery of sequence motifs related to coexpression of genes using evolutionary computation","volume":"32","author":"Fogel","year":"2004","journal-title":"Nucleic Acids Res"},{"key":"2023051706080503400_btaa775-B12","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1038\/nature04532","article-title":"Proteome survey reveals modularity of the yeast cell machinery","volume":"440","author":"Gavin","year":"2006","journal-title":"Nature"},{"key":"2023051706080503400_btaa775-B13","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1111\/j.1365-313X.2007.03133.x","article-title":"The R2R3-MYB transcription factor HAG1\/MYB28 IS a regulator of methionine-derived glucosinolate biosynthesis in Arabidopsis thaliana","volume":"51","author":"Gigolashvili","year":"2007","journal-title":"Plant Journal"},{"key":"2023051706080503400_btaa775-B14","doi-asserted-by":"crossref","first-page":"7821","DOI":"10.1073\/pnas.122653799","article-title":"Community structure in social and biological networks","volume":"99","author":"Girvan","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023051706080503400_btaa775-B15","doi-asserted-by":"crossref","first-page":"D364","DOI":"10.1093\/nar\/gki053","article-title":"CYGD: the comprehensive yeast genome database","volume":"33","author":"G\u00fcldener","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"2023051706080503400_btaa775-B16","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1109\/TCBB.2016.2642107","article-title":"Evolutionary graph clustering for protein complex identification","volume":"15","author":"He","year":"2018","journal-title":"IEEE\/ACM Trans. Comput. Biol. Bioinform"},{"key":"2023051706080503400_btaa775-B17","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1109\/TCBB.2018.2822709","article-title":"Measuring boundedness for protein complex identification in PPI networks","volume":"16","author":"He","year":"2019","journal-title":"IEEE\/ACM Trans. Comput. Biol. Bioinform"},{"key":"2023051706080503400_btaa775-B18","first-page":"1","article-title":"Contextual correlation preserving multiview featured graph clustering","author":"He","year":"2019","journal-title":"IEEE Trans. Cybern"},{"key":"2023051706080503400_btaa775-B19","doi-asserted-by":"crossref","first-page":"6478","DOI":"10.1073\/pnas.0611629104","article-title":"Omics-based identification of Arabidopsis Myb transcription factors regulating aliphatic glucosinolate biosynthesis","volume":"104","author":"Hirai","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023051706080503400_btaa775-B20","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1109\/TCBB.2013.37","article-title":"Utilizing both topological and attribute information for protein complex identification in PPI networks","volume":"10","author":"Hu","year":"2013","journal-title":"IEEE\/ACM Trans. Comput. Biol. Bioinform"},{"key":"2023051706080503400_btaa775-B21","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1109\/TCBB.2018.2844256","article-title":"Efficiently detecting protein complexes from protein interaction networks via alternating direction method of multipliers","volume":"16","author":"Hu","year":"2019","journal-title":"IEEE\/ACM Trans. Comput. Biol. Bioinform"},{"key":"2023051706080503400_btaa775-B22","first-page":"1","article-title":"A variational Bayesian framework for cluster analysis in a complex network","author":"Hu","year":"2019","journal-title":"IEEE Trans. Knowl. Data Eng"},{"key":"2023051706080503400_btaa775-B23","doi-asserted-by":"crossref","first-page":"D1057","DOI":"10.1093\/nar\/gku1113","article-title":"The GOA database: gene ontology annotation updates for 2015","volume":"43","author":"Huntley","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"2023051706080503400_btaa775-B24","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.1093\/emboj\/21.10.2441","article-title":"PIF4, a phytochrome-interacting bHLH factor, functions as a negative regulator of phytochrome B signaling in Arabidopsis","volume":"21","author":"Huq","year":"2002","journal-title":"EMBO J"},{"key":"2023051706080503400_btaa775-B25","doi-asserted-by":"crossref","first-page":"5280","DOI":"10.1073\/pnas.0408941102","article-title":"An Arabidopsis transcription factor, AtbZIP60, regulates the endoplasmic reticulum stress response in a manner unique to plants","volume":"102","author":"Iwata","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023051706080503400_btaa775-B26","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/S1360-1385(01)02223-3","article-title":"bZIP transcription factors in Arabidopsis","volume":"7","author":"Jakoby","year":"2002","journal-title":"Trends Plant Sci"},{"key":"2023051706080503400_btaa775-B27","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1093\/bioinformatics\/btq078","article-title":"SPICi: a fast clustering algorithm for large biological networks","volume":"26","author":"Jiang","year":"2010","journal-title":"Bioinformatics"},{"key":"2023051706080503400_btaa775-B28","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1038\/nature04670","article-title":"Global landscape of protein complexes in the yeast Saccharomyces cerevisiae","volume":"440","author":"Krogan","year":"2006","journal-title":"Nature"},{"key":"2023051706080503400_btaa775-B29","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1093\/bioinformatics\/btr082","article-title":"The effects of feedback loops on disease comorbidity in human signaling networks","volume":"27","author":"Le","year":"2011","journal-title":"Bioinformatics"},{"key":"2023051706080503400_btaa775-B30","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1186\/1471-2164-11-S1-S3","article-title":"Computational approaches for detecting protein complexes from protein interaction networks: a survey","volume":"11","author":"Li","year":"2010","journal-title":"BMC Genomics"},{"key":"2023051706080503400_btaa775-B31","doi-asserted-by":"crossref","first-page":"e1003840","DOI":"10.1371\/journal.pgen.1003840","article-title":"Incorporating motif analysis into gene co-expression networks reveals novel modular expression pattern and new signaling pathways","volume":"9","author":"Ma","year":"2013","journal-title":"PLoS Genet"},{"key":"2023051706080503400_btaa775-B32","doi-asserted-by":"crossref","first-page":"D559","DOI":"10.1093\/nar\/gky973","article-title":"CORUM: the comprehensive resource of mammalian protein complexes\u20142019","volume":"47","author":"Madalina","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"2023051706080503400_btaa775-B33","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/nmeth.1938","article-title":"Detecting overlapping protein complexes in protein-protein interaction networks","volume":"9","author":"Nepusz","year":"2012","journal-title":"Nat. Methods"},{"key":"2023051706080503400_btaa775-B34","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1186\/s12859-016-1191-6","article-title":"Protein complex prediction for large protein protein interaction networks with the core&peel method","volume":"17","author":"Pellegrini","year":"2016","journal-title":"BMC Bioinformatics"},{"key":"2023051706080503400_btaa775-B35","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1038\/35021093","article-title":"Molecular portraits of human breast tumours","volume":"406","author":"Perou","year":"2000","journal-title":"Nature"},{"key":"2023051706080503400_btaa775-B36","doi-asserted-by":"crossref","first-page":"e343","DOI":"10.1371\/journal.pbio.0030343","article-title":"Dynamic properties of network motifs contribute to biological network organization","volume":"3","author":"Prill","year":"2005","journal-title":"PLoS Biol"},{"key":"2023051706080503400_btaa775-B37","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1093\/nar\/gkn1005","article-title":"Up-to-date catalogues of yeast protein complexes","volume":"37","author":"Pu","year":"2009","journal-title":"Nucleic Acids Res"},{"key":"2023051706080503400_btaa775-B38","doi-asserted-by":"crossref","first-page":"449D","DOI":"10.1093\/nar\/gkh086","article-title":"The database of interacting proteins: 2004 update","volume":"32","author":"Salwinski","year":"2004","journal-title":"Nucleic Acids Res"},{"key":"2023051706080503400_btaa775-B39","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.cell.2010.09.050","article-title":"SnapShot: network motifs","volume":"143","author":"Shoval","year":"2010","journal-title":"Cell"},{"key":"2023051706080503400_btaa775-B40","doi-asserted-by":"crossref","first-page":"e31929","DOI":"10.1371\/journal.pone.0031929","article-title":"Hierarchical information clustering by means of topologically embedded graphs","volume":"7","author":"Song","year":"2012","journal-title":"PLoS One"},{"key":"2023051706080503400_btaa775-B41","doi-asserted-by":"crossref","first-page":"3920","DOI":"10.1093\/bioinformatics\/btaa236","article-title":"MONET: a toolbox integrating top-performing methods for network modularisation","volume":"36","author":"Tomasoni","year":"2020","journal-title":"Bioinformatics"},{"key":"2023051706080503400_btaa775-B42","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1111\/j.1365-313X.2009.03976.x","article-title":"The GLABRA2 homeodomain protein directly regulates CESA5 and XTH17 gene expression in Arabidopsis roots","volume":"60","author":"Tominaga-Wada","year":"2009","journal-title":"Plant J"},{"key":"2023051706080503400_btaa775-B43","author":"Van Dongen","year":"2000"},{"key":"2023051706080503400_btaa775-B44","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1093\/bioinformatics\/btl038","article-title":"FANMOD: a tool for fast network motif detection","volume":"22","author":"Wernicke","year":"2006","journal-title":"Bioinformatics"},{"key":"2023051706080503400_btaa775-B45","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1093\/bib\/bbr033","article-title":"Biological network motif detection: principles and practice","volume":"13","author":"Wong","year":"2012","journal-title":"Brief. Bioinform"},{"key":"2023051706080503400_btaa775-B46","first-page":"2559","author":"Wu","year":"2016"},{"key":"2023051706080503400_btaa775-B47","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1111\/ppl.12638","article-title":"OsTGAP1 is responsible for JA-inducible diterpenoid phytoalexin biosynthesis in rice roots with biological impacts on allelopathic interaction","volume":"161","author":"Yoshida","year":"2017","journal-title":"Physiol. Plant"},{"key":"2023051706080503400_btaa775-B48","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1186\/1471-2105-14-163","article-title":"Protein complex detection using interaction reliability assessment and weighted clustering coefficient","volume":"14","author":"Zaki","year":"2013","journal-title":"BMC Bioinformatics"},{"key":"2023051706080503400_btaa775-B49","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1186\/1471-2105-15-186","article-title":"Detecting overlapping protein complexes based on a generative model with functional and topological properties","volume":"15","author":"Zhang","year":"2014","journal-title":"BMC Bioinformatics"},{"key":"2023051706080503400_btaa775-B50","doi-asserted-by":"crossref","first-page":"3184","DOI":"10.1093\/bioinformatics\/btz051","article-title":"DiffNetFDR: differential network analysis with false discovery rate control","volume":"35","author":"Zhang","year":"2019","journal-title":"Bioinformatics"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btaa775\/35056174\/btaa775.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/37\/4\/542\/50359883\/btaa775.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/37\/4\/542\/50359883\/btaa775.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T06:16:56Z","timestamp":1684304216000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/37\/4\/542\/5906025"}},"subtitle":[],"editor":[{"given":"Bonnie","family":"Berger","sequence":"additional","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2020,9,15]]},"references-count":50,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,5,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btaa775","relation":{},"ISSN":["1367-4803","1367-4811"],"issn-type":[{"value":"1367-4803","type":"print"},{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,2,15]]},"published":{"date-parts":[[2020,9,15]]}}}