Motivation: Helix–helix interactions play a critical role in the structure assembly, stability and function of membrane proteins. On the molecular level, the interactions are mediated by one or more residue contacts. Although previous studies focused on helix-packing patterns and sequence motifs, few of them developed methods specifically for contact prediction.Results: We present a new hierarchical framework for contact prediction, with an application in membrane proteins. The hierarchical scheme consists of two levels: in the first level, contact residues are predicted from the sequence and their pairing relationships are further predicted in the second level. Statistical analyses on contact propensities are combined with other sequence and structural information for training the support vector machine classifiers. Evaluated on 52 protein chains using leave-one-out cross validation (LOOCV) and an independent test set of 14 protein chains, the two-level approach consistently improves the conventional direct approach in prediction accuracy, with 80% reduction of input for prediction. Furthermore, the predicted contacts are then used to infer interactions between pairs of helices. When at least three predicted contacts are required for an inferred interaction, the accuracy, sensitivity and specificity are 56%, 40% and 89%, respectively. Our results demonstrate that a hierarchical framework can be applied to eliminate false positives (FP) while reducing computational complexity in predicting contacts. Together with the estimated contact propensities, this method can be used to gain insights into helix-packing in membrane proteins.Availability: http://bio-cluster.iis.sinica.edu.tw/TMhit/Contact: tsung@iis.sinica.edu.twSupplementary information:Supplementary data are available at Bioinformatics online.

This work examines the robustness of selfattentive neural networks against adversarial input perturbations. Specifically, we investigate the attention and feature extraction mechanisms of state-of-the-art recurrent neural networks and self-attentive architectures for sentiment analysis, entailment and machine translation under adversarial attacks. We also propose a novel attack algorithm for generating more natural adversarial examples that could mislead neural models but not humans. Experimental results show that, compared to recurrent neural models, self-attentive models are more robust against adversarial perturbation. In addition, we provide theoretical explanations for their superior robustness to support our claims.