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  Learning from past treatments and their outcome improves prediction of In Vivo response to anti-HIV therapy

Saigo, H., Altmann, A., Bogojeska, J., Müller, F., Nowozin, S., & Lengauer, T. (2011). Learning from past treatments and their outcome improves prediction of In Vivo response to anti-HIV therapy. Statistical Applications in Genetics and Molecular Biology, 10(1): 6, pp. 1-32. doi:10.2202/1544-6115.1604.

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 Creators:
Saigo, H, Author
Altmann, A, Author
Bogojeska, J, Author
Müller, F, Author
Nowozin, S1, 2, Author              
Lengauer, T, Author
Affiliations:
1Department Empirical Inference, Max Planck Institute for Biological Cybernetics, Max Planck Society, ou_1497795              
2Max Planck Institute for Biological Cybernetics, Max Planck Society, Spemannstrasse 38, 72076 Tübingen, DE, ou_1497794              

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 Abstract: Infections with the human immunodeficiency virus type 1 (HIV-1) are treated with combinations of drugs. Unfortunately, HIV responds to the treatment by developing resistance mutations. Consequently, the genome of the viral target proteins is sequenced and inspected for resistance mutations as part of routine diagnostic procedures for ensuring an effective treatment. For predicting response to a combination therapy, currently available computer-based methods rely on the genotype of the virus and the composition of the regimen as input. However, no available tool takes full advantage of the knowledge about the order of and the response to previously prescribed regimens. The resulting high-dimensional feature space makes existing methods difficult to apply in a straightforward fashion. The machine learning system proposed in this work, sequence boosting, is tailored to exploiting such high-dimensional information, i.e. the extraction of longitudinal features, by utilizing the recent advancements in data mining and boosting. When applied to predicting the latest treatment outcome for 3,759 treatment-experienced patients from the EuResist integrated database, sequence boosting achieved superior performance compared to SVMs with RBF kernels. Moreover, sequence boosting allows an easy access to the discriminative treatment information. Analysis of feature importance values provided by our model confirmed known facts regarding HIV treatment. For instance, application of potent and recently licensed drugs was beneficial for patients, and, conversely, the patient group that was subject to NRTI mono-therapies in the past had poor treatment perspectives today. Furthermore, our model revealed novel biological insights. More precisely, the combination of previously used drugs with their in vivo response is more informative than the information of previously used drugs alone. Using this information improves the performance of systems for predicting therapy outcome.

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Language(s): eng - English
 Dates: 2011-01
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.2202/1544-6115.1604
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Title: Statistical Applications in Genetics and Molecular Biology
Source Genre: Journal
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Publ. Info: Berkeley, CA : Berkeley Electronic Press
Pages: - Volume / Issue: 10 (1) Sequence Number: 6 Start / End Page: 1 - 32 Identifier: ISSN: 1544-6115
CoNE: https://pure.mpg.de/cone/journals/resource/111055796786000