Optimizing the PROTREC network-based missing protein prediction algorithm.

This article summarizes the PROTREC method and investigates the impact that the different hyper-parameters have on the task of missing protein prediction using PROTREC. We evaluate missing protein recovery rates using different PROTREC score selection approaches (MAX, MIN, MEDIAN, and MEAN), different PROTREC score thresholds, as well as different complex size thresholds. In addition, we included two additional cancer datasets in our analysis and introduced a new validation method to check both the robustness of the PROTREC method as well as the correctness of our analysis. Our analysis showed that the missing protein recovery rate can be improved by adopting PROTREC score selection operations of MIN, MEDIAN, and MEAN instead of the default MAX. However, this may come at a cost of reduced numbers of proteins predicted and validated. The users should therefore choose their hyper-parameters carefully to find a balance in the accuracy-quantity trade-off. We also explored the possibility of combining PROTREC with a p-value-based method (FCS) and demonstrated that PROTREC is able to perform well independently without any help from a p-value-based method. Furthermore, we conducted a downstream enrichment analysis to understand the biological pathways and protein networks within the cancerous tissues using the recovered proteins. Missing protein recovery rate using PROTREC can be improved by selecting a different PROTREC score selection method. Different PROTREC score selection methods and other hyper-parameters such as PROTREC score threshold and complex size threshold introduce accuracy-quantity trade-off. PROTREC is able to perform well independently of any filtering using a p-value-based method. Verification of the PROTREC method on additional cancer datasets. Downstream Enrichment Analysis to understand the biological pathways and protein networks in cancerous tissues.