{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:09:46Z","timestamp":1772158186275,"version":"3.50.1"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"21","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: Cancer progression and development are initiated by aberrations in various molecular networks through coordinated changes across multiple genes and pathways. It is important to understand how these networks change under different stress conditions and\/or patient-specific groups to infer differential patterns of activation and inhibition. Existing methods are limited to correlation networks that are independently estimated from separate group-specific data and without due consideration of relationships that are conserved across multiple groups.<\/jats:p><jats:p>Method: We propose a pathway-based differential network analysis in genomics (DINGO) model for estimating group-specific networks and making inference on the differential networks. DINGO jointly estimates the group-specific conditional dependencies by decomposing them into global and group-specific components. The delineation of these components allows for a more refined picture of the major driver and passenger events in the elucidation of cancer progression and development.<\/jats:p><jats:p>Results: Simulation studies demonstrate that DINGO provides more accurate group-specific conditional dependencies than achieved by using separate estimation approaches. We apply DINGO to key signaling pathways in glioblastoma to build differential networks for long-term survivors and short-term survivors in The Cancer Genome Atlas. The hub genes found by mRNA expression, DNA copy number, methylation and microRNA expression reveal several important roles in glioblastoma progression.<\/jats:p><jats:p>Availability and implementation: R Package at: odin.mdacc.tmc.edu\/\u223cvbaladan.<\/jats:p><jats:p>Contact: \u00a0veera@mdanderson.org<\/jats:p><jats:p>Supplementary information: Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btv406","type":"journal-article","created":{"date-parts":[[2015,7,7]],"date-time":"2015-07-07T01:11:11Z","timestamp":1436231471000},"page":"3413-3420","source":"Crossref","is-referenced-by-count":112,"title":["DINGO: differential network analysis in genomics"],"prefix":"10.1093","volume":"31","author":[{"given":"Min Jin","family":"Ha","sequence":"first","affiliation":[{"name":"Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}]},{"given":"Veerabhadran","family":"Baladandayuthapani","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}]},{"given":"Kim-Anh","family":"Do","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}]}],"member":"286","published-online":{"date-parts":[[2015,7,6]]},"reference":[{"key":"2023020202324314300_btv406-B1","doi-asserted-by":"crossref","first-page":"e29348","DOI":"10.1371\/journal.pone.0029348","article-title":"Comparing statistical methods for constructing large scale gene networks","volume":"7","author":"Allen","year":"2012","journal-title":"PLoS One"},{"key":"2023020202324314300_btv406-B2","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1126\/science.1195618","article-title":"Rewiring of genetic networks in response to DNA damage","volume":"330","author":"Bandyopadhyay","year":"2010","journal-title":"Science"},{"key":"2023020202324314300_btv406-B3","first-page":"485","article-title":"Model selection through sparse maximum likelihood estimation for multivariate Gaussian or binary data","volume":"9","author":"Banerjee","year":"2008","journal-title":"J. Machine Learning Res."},{"key":"2023020202324314300_btv406-B4","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1126\/science.286.5439.509","article-title":"Emergence of scaling in random networks","volume":"286","author":"Barab\u00e1si","year":"1999","journal-title":"Science"},{"key":"2023020202324314300_btv406-B5","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/nrg3013","article-title":"Towards systematic functional characterization of cancer genomes","volume":"12","author":"Boehm","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"2023020202324314300_btv406-B6","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/msb.2010.117","article-title":"Rewiring makes the difference","volume":"7","author":"Califano","year":"2011","journal-title":"Mol. Syst. Biol."},{"key":"2023020202324314300_btv406-B7","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/nrc3138","article-title":"Cancer research: past, present and future","volume":"11","author":"Cao","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"2023020202324314300_btv406-B8","doi-asserted-by":"crossref","first-page":"6479","DOI":"10.1158\/1078-0432.CCR-09-0889","article-title":"MYC-induced cancer cell energy metabolism and therapeutic opportunities","volume":"15","author":"Dang","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"2023020202324314300_btv406-B9","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.tig.2010.05.001","article-title":"From differential expression to differential networking\u2014identification of dysfunctional regulatory networks in diseases","volume":"26","author":"de la Fuente","year":"2010","journal-title":"Trends Genet."},{"key":"2023020202324314300_btv406-B11","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1214\/08-AOAS215","article-title":"Network exploration via the adaptive lasso and scad penalties","volume":"3","author":"Fan","year":"2009","journal-title":"Ann. Appl. Stat."},{"key":"2023020202324314300_btv406-B12","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1038\/nrg1476","article-title":"Rewiring the network","volume":"5","author":"Flintoft","year":"2004","journal-title":"Nat. Rev. Genet."},{"key":"2023020202324314300_btv406-B13","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1093\/biostatistics\/kxm045","article-title":"Sparse inverse covariance estimation with the graphical lasso","volume":"9","author":"Friedman","year":"2008","journal-title":"Biostatistics"},{"key":"2023020202324314300_btv406-B14","doi-asserted-by":"crossref","first-page":"2683","DOI":"10.1101\/gad.1596707","article-title":"Malignant astrocytic glioma: genetics, biology, and paths to treatment","volume":"21","author":"Furnari","year":"2007","journal-title":"Genes Dev."},{"key":"2023020202324314300_btv406-B15","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1093\/bioinformatics\/btm051","article-title":"Analyzing gene expression data in terms of gene sets: methodological issues","volume":"23","author":"Goeman","year":"2007","journal-title":"Bioinformatics"},{"key":"2023020202324314300_btv406-B16","doi-asserted-by":"crossref","first-page":"729","DOI":"10.5705\/ss.2010.051","article-title":"A covariance regression model","volume":"22","author":"Hoff","year":"2012","journal-title":"Stat. Sin."},{"key":"2023020202324314300_btv406-B17","doi-asserted-by":"crossref","first-page":"e1000382","DOI":"10.1371\/journal.pcbi.1000382","article-title":"A differential wiring analysis of expression data correctly identifies the gene containing the causal mutation","volume":"5","author":"Hudson","year":"2009","journal-title":"PLoS Comput. Biol."},{"key":"2023020202324314300_btv406-B18","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/msb.2011.99","article-title":"Differential network biology","volume":"8","author":"Ideker","year":"2012","journal-title":"Mol. Syst. Biol."},{"key":"2023020202324314300_btv406-B19","doi-asserted-by":"crossref","first-page":"e1002375","DOI":"10.1371\/journal.pcbi.1002375","article-title":"Ten years of pathway analysis: current approaches and outstanding challenges","volume":"8","author":"Khatri","year":"2012","journal-title":"PLoS Comput. Biol."},{"key":"2023020202324314300_btv406-B20","doi-asserted-by":"crossref","DOI":"10.1093\/oso\/9780198522195.001.0001","volume-title":"Graphical Models","author":"Lauritzen","year":"1996"},{"key":"2023020202324314300_btv406-B21","doi-asserted-by":"crossref","first-page":"2637","DOI":"10.1093\/bioinformatics\/btq471","article-title":"DCGL: an R package for identifying differentially coexpressed genes and links from gene expression microarray data","volume":"26","author":"Liu","year":"2010","journal-title":"Bioinformatics"},{"key":"2023020202324314300_btv406-B22","doi-asserted-by":"crossref","first-page":"7570","DOI":"10.1073\/pnas.0712306105","article-title":"Cdk5-mediated regulation of the PIKE-A-Akt pathway and glioblastoma cell invasion","volume":"105","author":"Liu","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023020202324314300_btv406-B23","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1038\/nature02782","article-title":"Genomic analysis of regulatory network dynamics reveals large topological changes","volume":"431","author":"Luscombe","year":"2004","journal-title":"Nature"},{"key":"2023020202324314300_btv406-B24","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1186\/1471-2105-8-S6-S5","article-title":"Inferring cellular networks\u2014a review","volume":"8","author":"Markowetz","year":"2007","journal-title":"BMC Bioinformatics"},{"key":"2023020202324314300_btv406-B25","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/j.cmet.2013.09.013","article-title":"mTOR complex 2 controls glycolytic metabolism in glioblastoma through FoxO acetylation and upregulation of c-Myc","volume":"18","author":"Masui","year":"2013","journal-title":"Cell Metab."},{"key":"2023020202324314300_btv406-B26","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1038\/nature07385","article-title":"Comprehensive genomic characterization defines human glioblastoma genes and core pathways","volume":"455","author":"McLendon","year":"2008","journal-title":"Nature"},{"key":"2023020202324314300_btv406-B27","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1080\/0025570X.1981.11976898","article-title":"On the inverse of the sum of matrices","volume":"54","author":"Miller","year":"1981","journal-title":"Math. Mag."},{"key":"2023020202324314300_btv406-B28","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1111\/j.1750-3639.2003.tb00006.x","article-title":"Targeted molecular therapy of GBM","volume":"13","author":"Mischel","year":"2003","journal-title":"Brain Pathol."},{"key":"2023020202324314300_btv406-B29","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1038\/nrg3552","article-title":"Integrative approaches for finding modular structure in biological networks","volume":"14","author":"Mitra","year":"2013","journal-title":"Nat. Rev. Genet."},{"key":"2023020202324314300_btv406-B30","doi-asserted-by":"crossref","first-page":"278","DOI":"10.3389\/fphys.2013.00278","article-title":"Methods and approaches in the topology-based analysis of biological pathways","volume":"4","author":"Mitrea","year":"2013","journal-title":"Front. Physiol."},{"key":"2023020202324314300_btv406-B31","doi-asserted-by":"crossref","first-page":"e20038","DOI":"10.1371\/journal.pone.0020038","article-title":"The role of miR-103 and miR-107 in regulation of CDK5R1 expression and in cellular migration","volume":"6","author":"Moncini","year":"2011","journal-title":"PLoS One"},{"key":"2023020202324314300_btv406-B32","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S0014-2999(00)00809-8","article-title":"Extreme discordant phenotype methodology: an intuitive approach to clinical pharmacogenetics","volume":"410","author":"Nebert","year":"2000","journal-title":"Eur. J. Pharmacol."},{"key":"2023020202324314300_btv406-B33","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1093\/bioinformatics\/btt687","article-title":"Gene sets net correlations analysis (GSNCA): a multivariate differential coexpression test for gene sets","volume":"30","author":"Rahmatallah","year":"2014","journal-title":"Bioinformatics"},{"key":"2023020202324314300_btv406-B34","doi-asserted-by":"crossref","first-page":"2396","DOI":"10.1093\/bioinformatics\/btl392","article-title":"Simultaneous identification of differential gene expression and connectivity in inflammation, adipogenesis and cancer","volume":"22","author":"Reverter","year":"2006","journal-title":"Bioinformatics"},{"key":"2023020202324314300_btv406-B35","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/nature12415","article-title":"Integrative genomics identifies APOE \u03b54 effectors in Alzheimer\u2019s disease","volume":"500","author":"Rhinn","year":"2013","journal-title":"Nature"},{"key":"2023020202324314300_btv406-B36","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1214\/08-EJS176","article-title":"Sparse permutation invariant covariance estimation","volume":"2","author":"Rothman","year":"2008","journal-title":"Electron. J. Stat."},{"key":"2023020202324314300_btv406-B37","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/nature08454","article-title":"Molecular networks as sensors and drivers of common human diseases","volume":"461","author":"Schadt","year":"2009","journal-title":"Nature"},{"key":"2023020202324314300_btv406-B38","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1093\/bioinformatics\/btn577","article-title":"A novel signaling pathway impact analysis","volume":"25","author":"Tarca","year":"2009","journal-title":"Bioinformatics"},{"key":"2023020202324314300_btv406-B39","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/10343","article-title":"Systematic determination of genetic network architecture","volume":"22","author":"Tavazoie","year":"1999","journal-title":"Nat. Genet."},{"key":"2023020202324314300_btv406-B40","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/nbt.1522","article-title":"Dynamic modularity in protein interaction networks predicts breast cancer outcome","volume":"27","author":"Taylor","year":"2009","journal-title":"Nat. Biotechnol."},{"key":"2023020202324314300_btv406-B41","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1186\/1471-2105-11-497","article-title":"Diffcoex: a simple and sensitive method to find differentially coexpressed gene modules","volume":"11","author":"Tesson","year":"2010","journal-title":"BMC Bioinformatics"},{"key":"2023020202324314300_btv406-B42","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1111\/1467-9868.00196","article-title":"Probabilistic principal component analysis","volume":"61","author":"Tipping","year":"1999","journal-title":"J. R. Stat. Soc. B (Stat. Methodol.)"},{"key":"2023020202324314300_btv406-B43","doi-asserted-by":"crossref","first-page":"7277","DOI":"10.1158\/0008-5472.CAN-13-1868","article-title":"Combined targeting of PDK1 and EGFR triggers regression of glioblastoma by reversing the Warburg effect","volume":"73","author":"Velpula","year":"2013","journal-title":"Cancer Res."},{"key":"2023020202324314300_btv406-B44","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.ccr.2009.12.020","article-title":"Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1","volume":"17","author":"Verhaak","year":"2010","journal-title":"Cancer Cell"},{"key":"2023020202324314300_btv406-B45","doi-asserted-by":"crossref","first-page":"e3769","DOI":"10.1371\/journal.pone.0003769","article-title":"c-Myc is required for maintenance of glioma cancer stem cells","volume":"3","author":"Wang","year":"2008","journal-title":"PLoS One"},{"key":"2023020202324314300_btv406-B46","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1186\/1471-2105-7-509","article-title":"CoXpress: differential co-expression in gene expression data","volume":"7","author":"Watson","year":"2006","journal-title":"BMC Bioinformatics"},{"key":"2023020202324314300_btv406-B47","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1093\/neuonc\/nos117","article-title":"Current clinical development of PI3K pathway inhibitors in glioblastoma","volume":"14","author":"Wen","year":"2012","journal-title":"Neuro Oncol."},{"key":"2023020202324314300_btv406-B48","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1093\/biomet\/asm018","article-title":"Model selection and estimation in the Gaussian graphical model","volume":"94","author":"Yuan","year":"2007","journal-title":"Biometrika"},{"key":"2023020202324314300_btv406-B49","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1093\/bioinformatics\/btn660","article-title":"Differential dependency network analysis to identify condition-specific topological changes in biological networks","volume":"25","author":"Zhang","year":"2009","journal-title":"Bioinformatics"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/31\/21\/3413\/49035714\/bioinformatics_31_21_3413.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/31\/21\/3413\/49035714\/bioinformatics_31_21_3413.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,9]],"date-time":"2024-06-09T21:47:11Z","timestamp":1717969631000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/31\/21\/3413\/195238"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,7,6]]},"references-count":48,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2015,11,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btv406","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2015,11,1]]},"published":{"date-parts":[[2015,7,6]]}}}