Biomedical subjects

Benjamin Good

Publications and source records attributed to Benjamin Good.

3 recordsLinked to original sources

PubMed2005

Semen-specific genetic characteristics of human immunodeficiency virus type 1 env.

Human immunodeficiency virus type 1 (HIV-1) in the male genital tract may comprise virus produced locally in addition to virus transported from the circulation. Virus produced in the male genital tract may be genetically distinct, due to tissue-specific cellular characteristics and immunological pressures. HIV-1 env sequences derived from paired blood and semen samples from the Los Alamos HIV Sequence Database were analyzed to ascertain a male genital tract-specific viral signature. Machine learning algorithms could predict seminal tropism based on env sequences with accuracies exceeding 90%, suggesting that a strong genetic signature does exist for virus replicating in the male genital tract. Additionally, semen-derived viral populations exhibited constrained diversity (P < 0.05), decreased levels of positive selection (P < 0.025), decreased CXCR4 coreceptor utilization, and altered glycosylation patterns. Our analysis suggests that the male genital tract represents a distinct selective environment that contributes to the apparent genetic bottlenecks associated with the sexual transmission of HIV-1.

Computational Biology↗

PubMed2004

Genetic basis of hypersusceptibility to protease inhibitors and low replicative capacity of human immunodeficiency virus type 1 strains in primary infection.

The initial virus strains from as many as 12% of individuals with primary human immunodeficiency virus (HIV) infection have a 50% inhibitory concentration </=0.4-fold that of HIV type 1(NL4-3) (HIV-1(NL4-3)) to ritonavir (hypersusceptibility [HS]). There is also substantial variation in replicative capacity (RC) or an in vitro assay of the contributions of protease (PR) and reverse transcriptase to viral fitness. In chronically infected antiretrovirally treated patients, amprenavir HS has been associated with the mutation N88S in PR, but this mutation is not seen in untreated patients. In this study, virus strains from 182 cases of primary HIV infection were analyzed, and a highly significant association between HS and low RC (</=10% that of HIV-1(NL4-3)) was observed (P < 10(-6)). Multivariate analysis was used to determine the genotypic basis of ritonavir HS, analyzing all polymorphic amino acid sites and insertions from p7gag through PR. Decision tree models developed on the entire Gag-plus-PR data set and on PR alone gave overall correct classifications of 73 and 72%, respectively, on cross-validation. They were also able to predict low RC, with sensitivities of 69 and 62% and specificities of 84 and 70%, respectively. The analysis shows that ritonavir HS in untreated primary HIV infection is not associated with single mutations but with combinations of amino acids at polymorphic sites and that the same genotypes which confer HS to PR inhibitors confer low RC. This supports the view that variation in PR function is directly responsible for variation in fitness among strains in primary infection.

Decision Trees↗

PubMed2003

A new perspective on V3 phenotype prediction.

The particular coreceptor used by a strain of HIV-1 to enter a host cell is highly indicative of its pathology. HIV-1 coreceptor usage is primarily determined by the amino add sequences of the V3 loop region of the viral envelope glycoprotein. The canonical approach to sequence-based prediction of coreceptor usage was derived via statistical analysis of a less reliable and significantly smaller data set than is presently available. We aimed to produce a superior phenotypic classifier by applying modern machine learning (ML) techniques to the current database of V3 loop sequences with known phenotype. The trained classifiers along with the sequence data are available for public use at the supplementary website: http://genomiac2.ucsd.edu:8080/wetcat/v3.html and http://www.cs.waikato.ac.nz/ml/weka[corrected].

Amino Acid Sequence↗