Quantitative Proteomics and Phosphoproteomics Analyses Identify Sex-biased Protein Ontologies of <i>Schistosoma Japonicum</i>

Schistosoma japonicum (S. japonicum) is the causative agent of human schistosomiasis in Asia. Identification of differentially expressed proteins (DEPs) between males and females could elucidate critical signaling pathways underlying sexual maturation and egg production. In the study, quantitative proteome and phosphoproteome profiles were obtained for adult males and females of S. japonicum. In total, we identified 2710 unique proteins, including 2055 proteins and 924 phosphorylated proteins, and 252 (∼ 12.5%) non-phosphorylated and 209 (11.7%) phosphorylated DEPs between males and females. Combined with RNA sequencing, 22 non-phosphorylated DEPs exhibited corresponding mRNA-level changes. Meanwhile, several non-phosphorylated DEPs were shown to function in sex-biased biological processes, including vitellocyte development, oviposition, and parasite mobility by RNA interference. Furthermore, we annotated 96 kinases for S. japonicum, of which CMGC/MAPK and Atypical/RIO kinases are significantly activated in males, while CAMK/CAMKL, AGC/DMPK, and STE/STE7 kinases are activated in females. Finally, the potential drugs targeting these kinases were determined in silico, resulting in 28 kinases as potentially targetable by 30 FDA-approved drugs. Overall, our study provided a collection of evidence-based proteomic and phosphoproteomic resources of S. japonicum and identified sex-biased proteins, phosphopeptides, and kinases, which could serve as potentially effective targets for developing novel interventions against schistosomiasis.