Mutagenetic tree Fisher kernel improves prediction of HIV drug resistance from viral genotype

Starting with the work of Jaakkola and Haussler, a variety of approaches have been proposed for coupling domain-specific generative models with statistical learning methods. The link is established by a kernel function which provides a similarity measure based inherently on the underlying model. In computational biology, the full promise of this framework has rarely ever been exploited, as most kernels are derived from very generic models, such as sequence profiles or hidden Markov models. Here, we introduce the MTreeMix kernel, which is based on a generative model tailored to the underlying biological mechanism. Specifically, the kernel quantifies the similarity of evolutionary escape from antiviral drug pressure between two viral sequence samples. We compare this novel kernel to a standard, evolution-agnostic amino acid encoding in the prediction of HIV drug resistance from genotype, using support vector regression. The results show significant improvements in predictive performance across 17 anti-HIV drugs. Thus, in our study, the generative-discriminative paradigm is key to bridging the gap between population genetic modeling and clinical decision making

HIV Drug Resistant Prediction and Featured Mutants Selection using Machine Learning Approaches

HIV/AIDS is widely spread and ranks as the sixth biggest killer all over the world. Moreover, due to the rapid replication rate and the lack of proofreading mechanism of HIV virus, drug resistance is commonly found and is one of the reasons causing the failure of the treatment. Even though the drug resistance tests are provided to the patients and help choose more efficient drugs, such experiments may take up to two weeks to finish and are expensive. Because of the fast development of the computer, drug resistance prediction using machine learning is feasible. In order to accurately predict the HIV drug resistance, two main tasks need to be solved: how to encode the protein structure, extracting the more useful information and feeding it into the machine learning tools; and which kinds of machine learning tools to choose. In our research, we first proposed a new protein encoding algorithm, which could convert various sizes of proteins into a fixed size vector. This algorithm enables feeding the protein structure information to most state of the art machine learning algorithms. In the next step, we also proposed a new classification algorithm based on sparse representation. Following that, mean shift and quantile regression were included to help extract the feature information from the data. Our results show that encoding protein structure using our newly proposed method is very efficient, and has consistently higher accuracy regardless of type of machine learning tools. Furthermore, our new classification algorithm based on sparse representation is the first application of sparse representation performed on biological data, and the result is comparable to other state of the art classification algorithms, for example ANN, SVM and multiple regression. Following that, the mean shift and quantile regression provided us with the potentially most important drug resistant mutants, and such results might help biologists/chemists to determine which mutants are the most representative candidates for further research