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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Learning Robust Multi-label Sample Specific Distances for Identifying HIV-1 Drug Resistance
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.
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- Award ID(s):
- 1652943
- NSF-PAR ID:
- 10129595
- Date Published:
- Journal Name:
- The Proceedings of the 23rd Annual International Conference on Research in Computational Molecular Biology (RECOMB 2019)
- Page Range / eLocation ID:
- 51-67
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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This article is categorized under:
Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease
Biology‐Inspired Nanomaterials > Protein and Virus‐Based Structures
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An antibiogram is a periodic summary of antibiotic resistance results of organisms from infected patients to selected antimicrobial drugs. Antibiograms help clinicians to understand regional resistance rates and select appropriate antibiotics in prescriptions. In practice, significant combinations of antibiotic resistance may appear in different antibiograms, forming antibiogram patterns. Such patterns may imply the prevalence of some infectious diseases in certain regions. Thus it is of crucial importance to monitor antibiotic resistance trends and track the spread of multi-drug resistant organisms. In this paper, we propose a novel problem of antibiogram pattern prediction that aims to predict which patterns will appear in the future. Despite its importance, tackling this problem encounters a series of challenges and has not yet been explored in the literature. First of all, antibiogram patterns are not i.i.d as they may have strong relations with each other due to genomic similarities of the underlying organisms. Second, antibiogram patterns are often temporally dependent on the ones that are previously detected. Furthermore, the spread of antibiotic resistance can be significantly influenced by nearby or similar regions. To address the above challenges, we propose a novel Spatial-Temporal Antibiogram Pattern Prediction framework, STAPP, that can effectively leverage the pattern correlations and exploit the temporal and spatial information. We conduct extensive experiments on a real-world dataset with antibiogram reports of patients from 1999 to 2012 for 203 cities in the United States. The experimental results show the superiority of STAPP against several competitive baselines.more » « less
- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Conference Paper:
- https://doi.org/10.1007/978-3-030-17083-7_4
