H-DROP: an SVM based helical domain linker predictor trained with features optimized by combining random forest and stepwise selection.

Abstract

Domain linker prediction is attracting much interest as it can help identifying novel domains suitable for high throughput proteomics analysis. Here, we report H-DROP, an SVM-based Helical Domain linker pRediction using OPtimal features. H-DROP is, to the best of our knowledge, the first predictor for specifically and effectively identifying helical linkers. This was made possible first because a large training dataset became available from IS-Dom, and second because we selected a small number of optimal features from a huge number of potential ones. The training helical linker dataset, which included 261 helical linkers, was constructed by detecting helical residues at the boundary regions of two independent structural domains listed in our previously reported IS-Dom dataset. 45 optimal feature candidates were selected from 3,000 features by random forest, which were further reduced to 26 optimal features by stepwise selection. The prediction sensitivity and precision of H-DROP were 35.2 and 38.8%, respectively. These values were over 10.7% higher than those of control methods including our previously developed DROP, which is a coil linker predictor, and PPRODO, which is trained with un-differentiated domain boundary sequences. Overall, these results indicated that helical linkers can be predicted from sequence information alone by using a strictly curated training data set for helical linkers and carefully selected set of optimal features. H-DROP is available at http://domserv.lab.tuat.ac.jp.