Identifying Schistosoma japonicum excretory/secretory proteins and their interactions with host immune system

Abstract

Schistosoma japonicum is a major infectious agent of schistosomiasis. It has been reported that large number of proteins excreted and secreted by S. japonicum during its life cycle are important for its infection and survival in definitive hosts. These proteins can be used as ideal candidates for vaccines or drug targets. In this work, we analyzed the protein sequences of S. japonicum and found that compared with other proteins in S. japonicum, excretory/secretory (ES) proteins are generally longer, more likely to be stable and enzyme, more likely to contain immune-related binding peptides and more likely to be involved in regulation and metabolism processes. Based on the sequence difference between ES and non-ES proteins, we trained a support vector machine (SVM) with much higher accuracy than existing approaches. Using this SVM, we identified 191 new ES proteins in S. japonicum, and further predicted 7 potential interactions between these ES proteins and human immune proteins. Our results are useful to understand the pathogenesis of schistosomiasis and can serve as a new resource for vaccine or drug targets discovery for anti-schistosome.

Figure 1. The average amino acid frequencies composition of SjSPs and SjBgPs.

Figure 2. The average percentage of nine physico-chemical classes of amino acids in SjSPs and SjBgPs.

Figure 3. Comparison of the distributions of other primary sequence features between SjSPs and SjBgPs.

Gravy: Grand average of hydropathicity. Extinction coefficient: an index indicates how much light a protein absorbs at a certain wavelength. Instability index: an estimate of the stability of your protein in a test tube.

Figure 4. The distributions of all post-modification features of SjSPs and SjBgPs.

NetCGlyc: C-mannosylation sites. NetNGlyc: N-linked glycosylation sites. NetOGlyc: O-GalNAc (mucin type) glycosylation sites. NetPhos_Ser: Ser phosphorylation sites. NetPhos_Thr: Thr phosphorylation sites. NetPhos_Tyr: Tyr phosphorylation sites.

Figure 5. The average composition of secondary structures of SjSPs and SjBgPs.

Figure 6. The distributions of all immune peptide features of SjSPs and SjBgPs.

BepiPred: linear B-cell peptides. NetChop: Human proteasome cleave sites.

Figure 7. The percentage of all signal peptides in SjSPs and SjBgPs.

SignalP: secretory pathway signal peptide predicted by SignalP program. Mitochondria: mitochondrial target sites. Nuclear: export nuclear target sites. Secretory: secreted via non-classical secretory pathway.

Figure 8. Potential protein protein interactions between Schistosoma japonicum and human.