Clearly, both proposed and demonstrated protein protein associations could help us in understanding the function of a protease within the parasite. For that reason, we constructed a network of P. falciparum proteins applying the protein protein associa tion data from STRING database, and analyzed these data, in conjunction together with the data from protein protein interaction assays employing the yeast two hybrid method, blood stage microarray experiments, proteo mics, literature text mining, and sequence homol ogy evaluation. The topology with the protein protein association network was analyzed along with the outcomes exam ined for facts as to how the proteases might func tion within the parasite. Sets of proteins connected with precise proteases or protease families had been extracted from the entire cell network to create protease asso ciated subnetworks and five of those subnetworks had been examined in detail.
Novel protease targets and pre viously unrecognized members of some sub systems may be postulated. ATP-competitive p38 MAPK inhibitor these insights support us to improved recognize the mechanisms underlying parasite metabo lism, cell cycle regulation, invasion and infection. Results and discussion Proteases are involved in complicated networks We downloaded and mined the protein protein associa tion information from the STRING database involving pro teins from P. falciparum. Seventy seven out of 124 predicted proteases have been found in this set and have been linked with no less than one other protein, constituting two,431 associations. Every asso ciation between a pair of proteins has a self-assurance score ranging from 0. 15 to 0.
999 that was inferred in the evidence employed to establish the association 221 associations reversible microtubule inhibitor have high self-assurance scores, 432 associations have medium self-assurance scores, and strikingly, 1,778 associations have relative low self-assurance scores. The massive proportion of low scored associations arises in the paucity of annotation data. Just before the genome of P. falciparum was sequenced, only about 20 proteins had been characterized. immediately after genome sequencing this num ber increased by two orders of magnitude, but more than 60% on the predicted gene solutions within the genome nevertheless had no functional assignment and ten years of subse quent work have reduced this quantity to roughly 45%. Consequently, info such as KEGG pathway assignments, PDB protein structures and reactome information, which have a tendency to enhance association scores, is scarce for P. falciparum. Thus, our subsequent evaluation is not going to exclude the associations with low confidence scores as they might effectively represent associations that have not been previously recognized. The degrees of connectivity vary among the 77 pre dicted proteases with protein protein associations, ran ging from one to 143.