COMTOP: Protein Residue–Residue Contact Prediction through Mixed Integer Linear Optimization

Protein contact prediction helps reconstruct the tertiary structure that greatly determines a protein’s function; therefore, contact prediction from the sequence is an important problem. Recently there has been exciting progress on this problem, but many of the existing methods are still low quality of prediction accuracy. In this paper, we present a new mixed integer linear programming (MILP)-based consensus method: a Consensus scheme based On a Mixed integer linear opTimization method for prOtein contact Prediction (COMTOP). The MILP-based consensus method combines the strengths of seven selected protein contact prediction methods, including CCMpred, EVfold, DeepCov, NNcon, PconsC4, plmDCA, and PSICOV, by optimizing the number of correctly predicted contacts and achieving a better prediction accuracy. The proposed hybrid protein residue–residue contact prediction scheme was tested in four independent test sets. For 239 highly non-redundant proteins, the method showed a prediction accuracy of 59.68%, 70.79%, 78.86%, 89.04%, 94.51%, and 97.35% for top-5L, top-3L, top-2L, top-L, top-L/2, and top-L/5 contacts, respectively. When tested on the CASP13 and CASP14 test sets, the proposed method obtained accuracies of 75.91% and 77.49% for top-L/5 predictions, respectively. COMTOP was further tested on 57 non-redundant ɑ-helical transmembrane proteins and achieved prediction accuracies of 64.34% and 73.91% for top-L/2 and top-L/5 predictions, respectively. For all test datasets, the improvement of COMTOP in accuracy over the seven individual methods increased with the increasing number of predicted contacts. For example, COMTOP performed much better for large number of contact predictions (such as top-5L and top-3L) than for small number of contact predictions such as top-L/2 and top-L/5. The results and analysis demonstrate that COMTOP can significantly improve the performance of the individual methods; therefore, COMTOP is more robust against different types of test sets. COMTOP also showed better/comparable predictions when compared with the state-of-the-art predictors.

DACE: Distribution-Aware Counterfactual Explanation by Mixed-Integer Linear Optimization

Counterfactual Explanation (CE) is one of the post-hoc explanation methods that provides a perturbation vector so as to alter the prediction result obtained from a classifier. Users can directly interpret the perturbation as an "action" for obtaining their desired decision results. However, an action extracted by existing methods often becomes unrealistic for users because they do not adequately care about the characteristics corresponding to the empirical data distribution such as feature-correlations and outlier risk. To suggest an executable action for users, we propose a new framework of CE for extracting an action by evaluating its reality on the empirical data distribution. The key idea of our proposed method is to define a new cost function based on the Mahalanobis' distance and the local outlier factor. Then, we propose a mixed-integer linear optimization approach to extracting an optimal action by minimizing our cost function. By experiments on real datasets, we confirm the effectiveness of our method in comparison with existing methods for CE.