A nonparametric test of gene region heterogeneity associated with phenotype

• 成果类型: Article
• 署名作者: Kowalski, J; Pagano, M; DeGruttola, V
• 署名单位: Johns Hopkins University; Johns Hopkins University; Harvard University
• 刊物名称: JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION
• ISSN/ISSBN: 0162-1459
• DOI: 10.1198/016214502760046952
• 发表日期: 2002
• 页码: 398-408
• 关键词: immunodeficiency-virus type-1; drug-resistance; substitutions; populations; management; genotype; distinct; therapy; blood

摘要

High-dimensional statistical problems arise in the investigation of the relationship between reduced sensitivity to antiretroviral drugs among human immunodeficiency virus-infected patients and viral genotypic patterns obtained from blood samples, This article develops a nonparametric approach for analyzing gene region heterogeneity associated with drug-resistance phenotype, The method is based on the distribution of distances between viral genetic sequences. The distance measures used are sufficiently flexible to allow weighting of locations within a gene region, as well as weighting of residue types within a location. The weighting may reflect covariability between locations and between residues within a location. The approach to inference presented extends U statistic theory to multivariate one- and two-sample cases, which leads to exact tests based on permutation theory and their asymptotic counterparts. These methods are applied to data from a study conducted by the AIDS Clinical Trials Group that investigated altered viral susceptibility to protease inhibitor drugs.