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MS evaluation of cardiac ion channel IPs. a, Workflow of the study. We performed MS measurements of immunoprecipitated channels and their interactors and of control IPs from quadruplicate murine cardiac tissue lysates. Deep proteome measurements of the membrane-enriched mouse heart samples utilized in the IP experiments were also performed. Bioinformatics network analyses prioritized interactors for functional evaluation. A subset of interactors were evaluated for their functional impact on cardiac electrophysiology by STORM imaging, optical mapping in zebrafish KOs, and patch clamping of cardiomyocytes from mice with interactor genes silenced. From multi-omics data integration, the impact of each interactor in human electrophysiology is evaluated. b, Dendrogram from unsupervised hierarchical cluster analysis of protein intensities of proteins identified in IP experiments show that the four replicate experiments all cluster together. The clustering follows the bait replicates. c, Pearson correlation coefficients for protein intensities of the four Cacna1c replicate pulldown experiments. Pearson correlation coefficients are indicated in each scatter plot. Parts of the figure were drawn by using pictures from Servier Medical Art. Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/). Source data
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