AT-TSVM: Improving Transmembrane Protein Inter-Helical Residue Contact Prediction Using Active Transfer Transductive Support Vector Machines

Alpha helical transmembrane proteins are a specific type of membrane proteins that consist of helices spanning the entire cell membrane. They make up almost a third of all transmembrane (TM) proteins and play a significant role in various cellular activities. The structural prediction of these proteins is crucial in understanding how they behave inside the cell and thus in identifying their functions. Despite their importance, only a small portion of TM proteins have had their structure determined experimentally. Inter-helical residue contact is one of the most successful computational approaches for reducing the TM protein fold search space and generating an acceptable 3D structure. Most current TM protein residue contact predictors use features extracted only from protein sequences to predict residue contacts. However, these features alone deliver a low-accuracy contact map and, as a result, a poor 3D structure. Although there are models that explore leveraging features extracted from protein 3D structures in order to produce a better representative contact model, such an approach remains theoretical, assuming the structure features are available, whereas in reality they are only available in the training data, but not in the test data, whose structure is what needs to be predicted. This presents a brand new transfer learning paradigm: training examples contain two sets of features, but test examples contain only one set of the less informative features. In this work, we propose a novel approach that can train a model with training examples that contain both sequence features and atomic features and apply the model on the test data that contain only sequence features but not atomic features, while still improving contact prediction rather than using sequence features alone. Specifically, our method, AT-TSVM, employs Active Transfer for Transductive Support Vector Machines, which is augmented with transfer, active learning and conventional transductive learning to enhance contact prediction accuracy. Results from a benchmark dataset show that our method can boost contact prediction accuracy by an average of 5 to 6% over the inductive classifier and 2.5 to 4% over the transductive classifier.