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Multi‐omics analysis reveals expression complexity and functional diversity of mouse kinome

Protein kinases are a crucial component of signaling pathways involved in a wide range of cellular responses, including growth, proliferation, differentiation, and migration. Systematic investigation of protein kinases is critical to better understand phosphorylation‐mediated signaling pathways and may provide insights into the development of potential therapeutic drug targets. Here we perform a systems‐level analysis of the mouse kinome by analyzing multi‐omics data. We used bulk and single‐cell transcriptomic data from the C57BL/6J mouse strain to define tissue‐ and cell‐type‐specific expression of protein kinases, followed by investigating variations in sequence and expression between C57BL/6J and DBA/2J strains. We then profiled a deep brain phosphoproteome from C57BL/6J and DBA/2J strains as well as their reciprocal hybrids to infer the activity of the mouse kinome. Finally, we performed phenome‐wide association analysis using the BXD recombinant inbred (RI) mice (a cross between C57BL/6J and DBA/2J strains) to identify any associations between variants in protein kinases and phenotypes. Collectively, our study provides a comprehensive analysis of the mouse kinome by investigating genetic sequence variation, tissue‐specific expression patterns, and associations with downstream phenotypes.