Use of the l1 norm for selection of sparse parameter sets that accurately predict drug response phenotype from viral genetic sequences.
We describe the use of the l1 norm for selection of a sparse set of model parameters that are used in the prediction of viral drug response, based on genetic sequence data of the Human Immunodeficiency Virus (HIV) reverse-transcriptase enzyme. We discuss the use of the l1 norm in the Least Absolute Selection and Shrinkage Operator (LASSO) regression model and the Support Vector Machine model. When tested by cross-validation with laboratory measurements, these models predict viral phenotype, or resistance, in response to Reverse-Transcriptase Inhibitors (RTIs) more accurately than other known models. The l1 norm is the most selective convex function, which sets a large proportion of the parameters to zero and also assures that a single optimal solution will be found, given a particular model formulation and training data set. A statistical model that reliably predicts viral drug response is an important tool in the selection of Anti-Retroviral Therapy. These techniques have general application to modeling phenotype from complex genetic data.
Matthew
Rabinowitz
R
Gene Security Network, Portola Valley, CA, USA.
Banjevic
Milena
M
Chan
A S
AS
Myers
Lance
L
Wolkowicz
Roland
R
Haberer
Jessica
J
Singer
Joshua
J
D000465:Algorithms; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D003663:Decision Trees; D024882:Drug Resistance, Viral / Q000235:genetics*; D005103:Expert Systems; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D015233:Models, Statistical; D009154:Mutation; D010641:Phenotype; D012044:Regression Analysis
D044966:Anti-Retroviral Agents; D054303:HIV Reverse Transcriptase