Integrated Proteome and Phosphoproteome Analyses Reveal Early- and Late-Stage Protein Networks of Traumatic Brain Injury.

Traumatic brain injury (TBI) is a major public health concern all around the world. Accumulating evidence suggests that pathological processes after brain injury continuously evolve. Here, we identified the differentially expressed proteins (DEPs) and differentially expressed phosphoproteins (DEPPs) in the early and late stages of TBI in mice using TMT labeling, enrichment of Phos affinity followed, and high-resolution LC-MS/MS analysis. Subsequently, integrative analyses, including functional enrichment-based clustering analysis, motif analysis, cross-talk pathway/process enrichment analysis, and protein-protein interaction enrichment analysis were performed to further identify the different and similar pathophysiologic mechanisms in the early and late stage. Our work reveals a map of early and late-stage protein networks in TBI, which shed light on useful biomarkers and the underlying mechanisms in TBI and its sequelae.