Volume 17 No 8 (2019)
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An Integrative Bioinformatics Framework for Linking Peripheral Biomarker Genes with Coronary Artery Disease
Ranjan K. Pradhan
Abstract
Coronary artery disease is the leading cause of mortality and morbidity worldwide and shows significant
biomarker diversity. Despite considerable progress in microarray and proteomics technologies, and therapeutic
strategies, the genetic basis of this disease remain poorly understood. High-throughput experiments such as
genome-wide association studies and microarray gene expression profiling offer valuable information to uncover
potential biomarkers associated with biochemical pathways and underlying mechanisms. Meta-analysis and
gene enrichment analysis are known to provide powerful tool to discover novel biomarkers and their associated
pathways using available genomic data on differentially expressed genes, measured under diverse conditions.
Although meta-analysis alone has shown to predict biomarker genes of cardiovascular diseases, its efficacy in
linking differentially expressed genes to coronary artery disease pathways along with other functional
enrichment tools is unclear. Specifically, identifying differentially expressed genes using meta-analysis is often
complicated by several factors such as the differences in microarray technique, study focus, data quality, gene
nomenclature, species, intervention, and the statistical models used for analysis. Therefore, in this work, we
developed a combined meta-analysis of multiple microarray data with quality control analysis, gene ontology
and pathways functional enrichment analysis to identify potential differentially expressed genes of coronary
artery disease and their cellular pathways. Gene expression data from four different studies were analyzed
individually and using meta-analysis of combined data, which results in five differentially expressed genes that
are thought to involve in coronary artery disease. This framework demonstrated the significance of microarray
data heterogeneity and selection of statistical measures in identifying potential biomarkers associated with
coronary artery disease, and can help elucidating the molecular mechanisms underlying this disease.
Keywords
Microarray Data; Differentially Expressed Genes; Gene Enrichment; Bioinformatics Analysis; Metaanalysis; Coronary Artery Disease
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