Quantitative proteomics and phosphoproteomics analyses identify sex-biased protein ontologies of Schistosoma japonicum

Schistosoma japonicum (S. japonicum) is one of the major causative agents of human schistosomiasis in Asia. Identification of differentially expressed proteins (DEPs) between male and female worms could reveal critical signaling pathways that are involved in sexual maturation and egg production. In the study, quantitative proteome and phosphoproteome profiles were obtained from adult male and female worms of S. japonicum. A total of 2,710 unique proteins, including 2,055 proteins and 924 phosphorylated proteins, were identified. We identifed 252 (~12.5%) non-phosphorylated and 209 (11.7%) phosphorylated DEPs between males and females. Combined with the RNA sequencing (RNA-seq) results, 22 non-phosphorylated DEPs exhibited corresponding mRNA-level changes. Next, several identified non-phosphorylated DEPs were further shown to be involved in sex-biased biological processes, including vitellocyte development, oviposition, and parasite mobility by RNA interference, which were also supported by their cellular niches by analyzing previously published single-cell RNA seq data. Furthermore, we annotated 96 kinases of S. japonicum based on the obtained phosphorylated proteins, of which CMGC/MAPK, Atypical/RIO are significantly activated in males, while CAMK/CAMKL, AGC/DMPK, and STE/STE7 are activated in females. Finally, the potential drugs targeting these kinases were determined in silico, resulting in the identification of 28 S. japonicum 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.