Learning Robust Multi-label Sample Specific Distances for Identifying HIV-1 Drug Resistance

Abstract

Acquired immunodeficiency syndrome (AIDS) is a syndrome caused by the human immunodeficiency virus (HIV). During the progression of AIDS, a patient’s the immune system is weakened, which increases the patient’s susceptibility to infections and diseases. Although antiretroviral drugs can effectively suppress HIV, the virus mutates very quickly and can become resistant to treatment. In addition, the virus can also become resistant to other treatments not currently being used through mutations, which is known in the clinical research community as cross-resistance. Since a single HIV strain can be resistant to multiple drugs, this problem is naturally represented as a multi-label classification problem. Given this multi-class relationship, traditional single-label classification methods usually fail to effectively identify the drug resistances that may develop after a particular virus mutation. In this paper, we propose a novel multi-label Robust Sample Specific Distance (RSSD) method to identify multi-class HIV drug resistance. Our method is novel in that it can illustrate the relative strength of the drug resistance of a reverse transcriptase sequence against a given drug nucleoside analogue and learn the distance metrics for all the drug resistances. To learn the proposed RSSDs, we formulate a learning objective that maximizes the ratio of the summations of a number of \(\ell _1\)-norm distances, which is difficult to solve in general. To solve this optimization problem, we derive an efficient, non-greedy, iterative algorithm with rigorously proved convergence. Our new method has been verified on a public HIV-1 drug resistance data set with over 600 RT sequences and five nucleoside analogues. We compared our method against other state-of-the-art multi-label classification methods and the experimental results have demonstrated the effectiveness of our proposed method.