title: Statistical insights into major human muscular diseases.
abstract: Muscular diseases lead to muscle fiber degeneration, impairment of mobility, and in some cases premature death. Many of these muscular diseases are largely idiopathic. The goal of this study was to identify biomarkers based on their functional role and possible mechanisms of pathogenesis, specific to individual muscular disease. We analyzed the muscle transcriptome from five major muscular diseases: acute quadriplegic myopathy (AQM), amyotrophic lateral sclerosis (ALS), mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), dermatomyositis (DM) and polymyositis (PM) using pairwise statistical comparison to identify uniquely regulated genes in each muscular disease. The genome-wide information encoded in the transcriptome provided biomarkers and functional insights into dysregulation in each muscular disease. The analysis showed that the dysregulation of genes in forward membrane pathway, responsible for transmitting action potential from neural excitation, is unique to AQM, while the dysregulation of myofibril genes, determinant of the mechanical properties of muscle, is unique to ALS, dysregulation of ER protein processing, responsible for correct protein folding, is unique to DM, and upregulation of immune response genes is unique to PM. We have identified biomarkers specific to each muscular disease which can be used for diagnostic purposes.
authors.affiliation: Department of Bioengineering.
authors.forename: Shakti
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Bioengineering.
authors.forename: Sung-Min
authors.initials: SM
authors.lastname: Kim
authors.affiliation: Department of Bioengineering.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Bioengineering.
authors.forename: Ashok Reddy
authors.initials: AR
authors.lastname: Dinasarapu
authors.affiliation: Department of Bioengineering, Department of Cellular and Molecular Medicine and Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA shankar@ucsd.edu.
authors.forename: Shankar
authors.initials: S
authors.lastname: Subramaniam
mesh_terms: D015415:Biomarkers / Q000032:analysis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D056726:Genetic Association Studies / Q000379:methods*; D006801:Humans; D015233:Models, Statistical; D009132:Muscles / Q000378:metabolism / Q000473:pathology; D009135:Muscular Diseases / Q000235:genetics* / Q000473:pathology*; D009928:Organ Specificity; D046888:Tissue Array Analysis
chemical_list: D015415:Biomarkers