An integrative proteogenomic examine reveals that human phospho-signaling networks responding to SARS-CoV-2 an infection are enriched in genetic variants that modify kinase binding motifs, suggesting that genetic variation could affect an infection and COVID-19 pathology.
SARS-CoV-2 an infection hijacks signaling pathways and induces protein–protein interactions between human and viral proteins. Human genetic variation could affect SARS-CoV-2 an infection and COVID-19 pathology; nevertheless, the genetic variation in these signaling networks stays uncharacterized. Right here, we studied human missense single nucleotide variants (SNVs) altering phosphorylation websites modulated by SARS-CoV-2 an infection, utilizing machine studying to establish amino acid substitutions altering kinase-bound sequence motifs. We discovered 2,033 rare phosphorylation-associated SNVs (pSNVs) which are enriched in sequence motif alterations, doubtlessly reflecting the evolution of signaling networks regulating host defenses. Proteins with pSNVs are concerned in viral life cycle and host responses, together with RNA splicing, interferon response (TRIM28), and glucose homeostasis (TBC1D4) with potential associations with COVID-19 comorbidities. pSNVs disrupt CDK and MAPK substrate motifs and substitute these with motifs of Tank Binding Kinase 1 (TBK1) concerned in innate immune responses, indicating constant rewiring of signaling networks. A number of pSNVs affiliate with extreme COVID-19 and hospitalization (STARD13, ARFGEF2). Our evaluation highlights potential genetic elements contributing to inter-individual variation of SARS-CoV-2 an infection and COVID-19 and suggests leads for mechanistic and translational research.