{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T01:53:13Z","timestamp":1774489993860,"version":"3.50.1"},"reference-count":32,"publisher":"World Scientific Pub Co Pte Lt","issue":"02a","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Bioinform. Comput. Biol."],"published-print":{"date-parts":[[2007,4]]},"abstract":"<jats:p> Cisplatin-induced drug resistance is known to involve a complex set of cellular changes whose molecular mechanism details remain unclear. In this study, we developed a systems biology approach to examine proteomics- and network-level changes between cisplatin-resistant and cisplatin-sensitive cell lines. This approach involves experimental investigation of differential proteomics profiles and computational study of activated enriched proteins, protein interactions, and protein interaction networks. Our experimental platform is based on a Label-free liquid Chromatography\/mass spectrometry proteomics platform. Our computational methods start with an initial list of 119 differentially expressed proteins. We expanded these proteins into a cisplatin-resistant activated sub-network using a database of human protein-protein interactions. An examination of network topology features revealed the activated responses in the network are closely coupled. By examining sub-network proteins using gene ontology categories, we found significant enrichment of proton-transporting ATPase and ATP synthase complexes activities in cisplatin-resistant cells in the form of cooperative down-regulations. Using two-dimensional visualization matrixes, we further found significant cascading of endogenous, abiotic, and stress-related signals. Using a visual representation of activated protein categorical sub-networks, we showed that molecular regulation of cell differentiation and development caused by responses to proteome-wide stress as a key signature to the acquired drug resistance. <\/jats:p>","DOI":"10.1142\/s0219720007002606","type":"journal-article","created":{"date-parts":[[2007,6,21]],"date-time":"2007-06-21T22:42:56Z","timestamp":1182465776000},"page":"383-405","source":"Crossref","is-referenced-by-count":17,"title":["A SYSTEMS BIOLOGY APPROACH TO THE STUDY OF CISPLATIN DRUG RESISTANCE IN OVARIAN CANCERS"],"prefix":"10.1142","volume":"05","author":[{"given":"JAKE Y.","family":"CHEN","sequence":"first","affiliation":[{"name":"Indiana University School of Informatics, and Department of Computer and Information Science, Purdue University School of Science, 535 W. Michigan Street, IT #493, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ZHONG","family":"YAN","sequence":"additional","affiliation":[{"name":"Indiana University School of Informatics, 535 W. Michigan Street, IT #492, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"CHANGYU","family":"SHEN","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, Indiana University School of Medicine, 1050 Wishard Blvd., RG R4101, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"DAWN P. G.","family":"FITZPATRICK","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 1345 West 16th Street, Room 345, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MU","family":"WANG","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Indiana University School of Medicine and INCAPS, (Indiana Centers for Applied Protein Sciences), 351 West 10th St, Suite 350, Indianapolis, IN 46202, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"219","published-online":{"date-parts":[[2011,11,21]]},"reference":[{"key":"rf1","first-page":"258","volume":"5","author":"Verrills N. 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