title: Integrative computational and experimental approaches to establish a post-myocardial infarction knowledge map.
abstract: Vast research efforts have been devoted to providing clinical diagnostic markers of myocardial infarction (MI), leading to over one million abstracts associated with "MI" and "Cardiovascular Diseases" in PubMed. Accumulation of the research results imposed a challenge to integrate and interpret these results. To address this problem and better understand how the left ventricle (LV) remodels post-MI at both the molecular and cellular levels, we propose here an integrative framework that couples computational methods and experimental data. We selected an initial set of MI-related proteins from published human studies and constructed an MI-specific protein-protein-interaction network (MIPIN). Structural and functional analysis of the MIPIN showed that the post-MI LV exhibited increased representation of proteins involved in transcriptional activity, inflammatory response, and extracellular matrix (ECM) remodeling. Known plasma or serum expression changes of the MIPIN proteins in patients with MI were acquired by data mining of the PubMed and UniProt knowledgebase, and served as a training set to predict unlabeled MIPIN protein changes post-MI. The predictions were validated with published results in PubMed, suggesting prognosticative capability of the MIPIN. Further, we established the first knowledge map related to the post-MI response, providing a major step towards enhancing our understanding of molecular interactions specific to MI and linking the molecular interaction, cellular responses, and biological processes to quantify LV remodeling.
authors.affiliation: Department of Electrical and Computer Engineering, University of Texas at San Antonio, San Antonio, Texas, United States of America; San Antonio Cardiovascular Proteomics Center, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
authors.forename: Nguyen T
authors.initials: NT
authors.lastname: Nguyen
authors.affiliation: Department of Electrical and Computer Engineering, University of Texas at San Antonio, San Antonio, Texas, United States of America.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Center for Bioinformatics and Computational Biology and Protein Information Resource, University of Delaware, Newark, Delaware, United States of America.
authors.forename: Cathy
authors.initials: C
authors.lastname: Wu
authors.affiliation: San Antonio Cardiovascular Proteomics Center, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America; Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lange
authors.affiliation: San Antonio Cardiovascular Proteomics Center, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America; Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Chilton
authors.affiliation: San Antonio Cardiovascular Proteomics Center, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America; Mississippi Center for Heart Research, University of Mississippi Medical Center, Jackson, Mississippi, United States of America; Research Service, G.V. (Sonny) Montgomery Veterans Affairs Medical Center, Jackson, Mississippi, United States of America.
authors.forename: Merry L
authors.initials: ML
authors.lastname: Lindsey
authors.affiliation: Department of Electrical and Computer Engineering, University of Texas at San Antonio, San Antonio, Texas, United States of America; San Antonio Cardiovascular Proteomics Center, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
authors.forename: Yu-Fang
authors.initials: YF
authors.lastname: Jin
mesh_terms: D000465:Algorithms; D015415:Biomarkers / Q000378:metabolism; D016000:Cluster Analysis; D003198:Computer Simulation; D057225:Data Mining; D030562:Databases, Protein; D005109:Extracellular Matrix / Q000502:physiology; D006352:Heart Ventricles / Q000473:pathology; D006801:Humans; D008490:Medical Informatics; D008954:Models, Biological; D009203:Myocardial Infarction / Q000175:diagnosis* / Q000503:physiopathology*; D025941:Protein Interaction Mapping; D020257:Ventricular Remodeling
chemical_list: D015415:Biomarkers