Benchmarking network propagation methods for disease gene identification

摘要

The use of biological network data has proven its effectiveness in many areas from computational biology. Networks consist of nodes, usually genes or proteins, and edges that connect pairs of nodes, representing information such as physical interactions, regulatory roles or co-occurrence. In order to find new candidate nodes for a given biological property, the so-called network propagation algorithms start from the set of known nodes with that property and leverage the connections from the biological network to make predictions. Here, we assess the performance of several network propagation algorithms to find sensible gene targets for 22 common non-cancerous diseases, i.e. those that have been found promising enough to start the clinical trials with any compound. We focus on obtaining performance metrics that reflect a practical scenario in drug development where only a small set of genes can be essayed. We found that the presence of protein complexes biased the performance estimates, leading to over-optimistic conclusions, and introduced two novel strategies to address it. Our results support that network propagation is still a viable approach to find drug targets, but that special care needs to be put on the validation strategy. Algorithms benefitted from the use of a larger -although noisier- network and of direct evidence data, rather than indirect genetic associations to disease.