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Proteomic analysis of DCM mouse hearts reveals activation of complement cascades and decreased protein abundance involved in glycogen metabolic processes.

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posted on 25.09.2017, 17:26 by Leslie Kennedy, Erin Kaltenbrun, Todd M. Greco, Brenda Temple, Laura E. Herring, Ileana M. Cristea, Frank L. Conlon

(A-B) Comparison of normalized protein abundances (black dots, n = 3164) quantified by TMT-based proteomics between biological replicates of (A) Nkx2.5Cre (Control, CTL) and (B) Tbx20flox/+; Casz1flox/+; Nkx2.5Cre (Mutant) mouse hearts. (C) Comparison of average normalized TMT protein abundances between Mutant and CTL mouse hearts (n = 2). Proteins classified as differentially abundant in the Mutant (TMT abundance ratios ≥ ±1/3-fold in both replicates) are indicated (red dots, n = 175). (D) Functional interaction network of differentially abundant proteins constructed using STRING interaction database. Proteins with up- and down-regulated abundances are represented by circle and square nodes, respectively, and labeled with primary gene symbols. Proteins that did not have connectivity to at least one other protein were excluded. Nodes are color-coded by cluster connectivity, which was assigned by the ReactomeF1 plug-in (see Methods). (See S7 Fig) Network edges reflect known STRING database relationships (confidence score >0.4). Edge thickness correlates with STRING confidence score (0.4–1). (E) Gene ontology (GO)-based network of selected over-represented Biological Processes represented by the differentially abundant proteins. Over-represented GO terms (p-value <0.05) are colored according to the proportion of the total differentially abundant proteins annotated to that term that were up- (yellow) or down- (blue) regulated. Protein to GO term assignments are indicated by network edges connecting the respective gene symbols (squares) with their assigned GO term.