AIDS is a syndrome caused by the HIV. During the progression of AIDS, a patient's 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 multilabel classification problem. Given this multilabel relationship, traditional single-label classification methods often fail to effectively identify the drug resistances that may develop after a particular virus mutation. In this work, we propose a novel multilabel Robust Sample Specific Distance (RSSD) method to identify multiclass HIV drug resistance. Our method is novel in that it can illustrate the relative strength of the drug resistance of a reverse transcriptase (RT) sequence against a given drug nucleoside analog 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 ℓ1-norm distances, which is difficult to solve in general. To solve this optimization problem, we derive an efficient, nongreedy iterative algorithm with rigorously proved convergence. Our new method has been verified on a public HIV type 1 drug resistance data set with over 600 RT sequences and five nucleoside analogs. We compared our method against several state-of-the-art multilabel classification methods, and the experimental results have demonstrated the effectiveness of our proposed method.
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A weak‐signal‐assisted procedure for variable selection and statistical inference with an informative subsample
This paper is motivated from an HIV‐1 drug resistance study where we encounter three analytical challenges: to analyze data with an informative subsample, to take into account the weak signals, and to detect important signals and also conduct statistical inference. We start with an initial estimation method, which adopts a penalized pairwise conditional likelihood approach for variable selection. This initial estimator incorporates the informative subsample issue. To accounting for the effect of weak signals, we use a key idea of partial ridge regression. We also propose a one‐step estimation method for each of the signal coefficients and then construct confidence intervals accordingly. We apply the proposed method to the Stanford HIV‐1 drug resistance study and compare the results with existing approaches. We also conduct comprehensive simulation studies to demonstrate the superior performance of our proposed method.
more » « less- Award ID(s):
- 2019461
- NSF-PAR ID:
- 10450068
- Publisher / Repository:
- Oxford University Press
- Date Published:
- Journal Name:
- Biometrics
- Volume:
- 77
- Issue:
- 3
- ISSN:
- 0006-341X
- Format(s):
- Medium: X Size: p. 996-1010
- Size(s):
- ["p. 996-1010"]
- Sponsoring Org:
- National Science Foundation
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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 ℓ1-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.more » « less
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