Generalized Hierarchical Sparse Model for Arbitrary-Order Interactive Antigenic Sites Identification in Flu Virus Data.

Recent statistical evidence has shown that a regression model by incorporating the interactions among the original covariates/features can significantly improve the interpretability for biological data. One major challenge is the exponentially expanded feature space when adding high-order feature interactions to the model. To tackle the huge dimensionality, hierarchical sparse models (HSM) are developed by enforcing sparsity under heredity structures in the interactions among the covariates. However, existing methods only consider pairwise interactions, making the discovery of important high-order interactions a non-trivial open problem. In this paper, we propose a generalized hierarchical sparse model (GHSM) as a generalization of the HSM models to tackle arbitrary-order interactions. The GHSM applies the ℓ penalty to all the model coefficients under a constraint that given any covariate, if none of its associated th-order interactions contribute to the regression model, then neither do its associated higher-order interactions. The resulting objective function is non-convex with a challenge lying in the coupled variables appearing in the arbitrary-order hierarchical constraints and we devise an efficient optimization algorithm to directly solve it. Specifically, we decouple the variables in the constraints via both the general iterative shrinkage and thresholding (GIST) and the alternating direction method of multipliers (ADMM) methods into three subproblems, each of which is proved to admit an efficiently analytical solution. We evaluate the GHSM method in both synthetic problem and the antigenic sites identification problem for the influenza virus data, where we expand the feature space up to the 5th-order interactions. Empirical results demonstrate the effectiveness and efficiency of the proposed methods and the learned high-order interactions have meaningful synergistic covariate patterns in the influenza virus antigenicity.