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. 2022 Apr 6;9:840647. doi: 10.3389/fcvm.2022.840647

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Copyright © 2022 Halawa, Latif, Tseng, Ibrahim, Chester, Moustafa, Aguib and Yacoub.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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PPI networks constructed upon the genes associated with differentially methylated promoters between non-diseased aortic and mitral valve tissue and the proteins that are necessary to interconnect them: (A) complete network, (B) subnetwork 1 (p-value 3.04e-13) and (C) subnetwork 2 (p-value 0.047). Depicted nodes are classified according to their methylation direction: nodes representing genes showing increased methylation in mitral compared to aortic tissue (red), nodes depicting increased methylation in aortic vs. mitral tissue (green) and nodes representing genes that are not part of the input dataset (gray). Node sizes are proportional to their betweenness centrality values. Betweenness centrality reflects the number of shortest paths passing through a node, while degree refers to the number of connections/edges/PPIs that a node has to other nodes. Hub nodes (A) UBC, SMAD3, UBL4A, RPS3, RXRA, (B) UBC and (C) BRCA2 and APOA5 can be clearly identified on the respective networks.