ArticleBMC medical informatics and decision making2011
Genotypic tropism testing by massively parallel sequencing: qualitative and quantitative analysis.
Article in BMC medical informatics and decision making, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Comparison of genotypic and phenotypic HIV type 1 tropism assay: results from the screening samples of Cenicriviroc Study 202, a randomized phase II trial in treatment-naive subjects.AIDS research and human retroviruses · 2014Trial
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- In-depth virological and immunological characterization of HIV-1 cure after CCR5Δ32/Δ32 allogeneic hematopoietic stem cell transplantation.Nature medicine · 2023Article
- Monophylogenetic HIV-1C epidemic in Ethiopia is dominated by CCR5-tropic viruses-an analysis of a prospective country-wide cohort.BMC infectious diseases · 2017Article
- Statistical correlation of nonconservative substitutions of HIV gp41 variable amino acid residues with the R5X4 HIV-1 phenotype.Virology journal · 2016Article
- HIV-1 Coreceptor Usage Assessment by Ultra-Deep Pyrosequencing and Response to Maraviroc.PloS one · 2015Article
- Article
- Bioinformatic analysis of HIV-1 entry and pathogenesis.Current HIV research · 2014Review
- HIV-1 tropism dynamics and phylogenetic analysis from longitudinal ultra-deep sequencing data of CCR5- and CXCR4-using variants.PloS one · 2014Article
- Using ultradeep pyrosequencing to study HIV-1 coreceptor usage in primary and dual infection.The Journal of infectious diseases · 2013Article
- Development of a novel codon-specific polymerase chain reaction for the detection of CXCR4-utilizing HIV type 1 subtype B.AIDS research and human retroviruses · 2013Article
- Sexual transmission of predicted CXCR4-tropic HIV-1 likely originating from the source partner's seminal cells.Virology · 2012Article
- Routine use of microbial whole genome sequencing in diagnostic and public health microbiology.PLoS pathogens · 2012Review
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInferring viral tropism from genotype is a fast and inexpensive alternative to phenotypic testing. While being highly predictive when performed on clonal samples, sensitivity of predicting CXCR4-using (X4) variants drops substantially in clinical isolates. This is mainly attributed to minor variants not detected by standard bulk-sequencing. Massively parallel sequencing (MPS) detects single clones thereby being much more sensitive. Using this technology we wanted to improve genotypic prediction of coreceptor usage.
methodsPlasma samples from 55 antiretroviral-treated patients tested for coreceptor usage with the Monogram Trofile Assay were sequenced with standard population-based approaches. Fourteen of these samples were selected for further analysis with MPS. Tropism was predicted from each sequence with geno2pheno[coreceptor].
resultsPrediction based on bulk-sequencing yielded 59.1% sensitivity and 90.9% specificity compared to the trofile assay. With MPS, 7600 reads were generated on average per isolate. Minorities of sequences with high confidence in CXCR4-usage were found in all samples, irrespective of phenotype. When using the default false-positive-rate of geno2pheno[coreceptor] (10%), and defining a minority cutoff of 5%, the results were concordant in all but one isolate.
conclusionsThe combination of MPS and coreceptor usage prediction results in a fast and accurate alternative to phenotypic assays. The detection of X4-viruses in all isolates suggests that coreceptor usage as well as fitness of minorities is important for therapy outcome. The high sensitivity of this technology in combination with a quantitative description of the viral population may allow implementing meaningful cutoffs for predicting response to CCR5-antagonists in the presence of X4-minorities.
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