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IV-KAPhE enables more robust and consistent kinase-activity inference.

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posted on 13.05.2022, 17:43 by Brandon M. Invergo

a) Target kinases and their downstream substrate kinases in a multi-inhibitor quantitative phosphoproteomics experiment [41] are expected to have altered enzymatic activities. Assignments derived from NetworKIN 3.0, GPS 5.0, and IV-KAPhE make stronger inferences than those from LinkPhinder or in vivo literature-derived annotations from PhosphoSitePlus, however these methods also erroneously predict increased activity in some target kinases and downstream substrate kinases that they enzymatically activate. Each column represents a different kinase inhibitor condition (see Table A in S1 Text), in which green dots are direct targets of the inhibitor, orange triangles are kinases that are enzymatically activated by a target kinase, and violet squares are kinases that are enzymatically inhibited by a target kinase. Gray, dashed lines indicate activity levels of -2.5 and 2.5, corresponding to Z-test p-values of 10−2.5. b) IV-KAPhE provides more consistent inference of negative activity in target kinases and substrate kinases that they enzymatically activate than other computational methods as well as in vivo literature-derived annotations from PhosphoSitePlus. Point colors and shapes, as well as the gray dashed lines, are as described for panel (a).

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