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Author, Editor(s)

Author(s):

Low, Andrew J.
Dong, Winnie
Chan, Dennison
Sing, Tobias
Swanstrom, Ronald
Jensen, Mark
Pillai, Satish
Good, Benjamin
Harrigan, P. Richard

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Not MPG Author(s):

Low, Andrew J.
Dong, Winnie
Chan, Dennison
Swanstrom, Ronald
Jensen, Mark
Pillai, Satish
Good, Benjamin
Harrigan, P. Richard

BibTeX cite key*:

LowDong2007

Title

Title*:

Current V3 genotyping algorithms are inadequate for predicting X4 co-receptor usage in clinical isolates

Journal

Journal Title*:

AIDS

Journal's URL:

http://www.aidsonline.com/

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Language:

English

Publisher

Publisher's
Name:

Lippincott Williams & Wilkins

Publisher's URL:


Publisher's
Address:


ISSN:

0269-9370

Vol, No, pp, Date

Volume*:

21

Number:

14

Publishing Date:

September 2007

Pages*:

F19-F26

Number of
VG Pages:


Page Start:

F19

Page End:

F26

Sequence Number:


DOI:


Note, Abstract, ©

Note:


(LaTeX) Abstract:

Objective: Integrating CCR5 antagonists into clinical practice would benefit from accurate assays of co-receptor usage (CCR5 versus CXCR4) with fast turnaround and low cost.
Design: Published HIV V3-loop based predictors of co-receptor usage were compared with actual phenotypic tropism results in a large cohort of antiretroviral naive individuals to determine accuracy on clinical samples and identify areas for improvement.
Methods: Aligned HIV envelope V3 loop sequences (n = 977), derived by bulk sequencing were analyzed by six methods: the 11/25 rule; a neural network (NN), two support vector machines, and two subtype-B position specific scoring matrices (PSSM). Co-receptor phenotype results (Trofile Co-receptor Phenotype Assay; Monogram Biosciences) were stratified by CXCR4 relative light unit (RLU) readout and CD4 cell count.
Results: Co-receptor phenotype was available for 920 clinical samples with V3 genotypes having fewer than seven amino acid mixtures (n = 769 R5; n = 151 X4-capable). Sensitivity and specificity for predicting X4 capacity were evaluated for the 11/25 rule (30% sensitivity/93% specificity), NN (44%/88%), PSSM(sinsi) (34%/96%), PSSM(x4r5) (24%/97%), SVMgenomiac (22%/90%) and SVMgeno2pheno (50%/89%). Quantitative increases in sensitivity could be obtained by optimizing the cut-off for methods with continuous output (PSSM methods), and/or integrating clinical data (CD4%). Sensitivity was directly proportional to strength of X4 signal in the phenotype assay (P < 0.05).
Conclusions: Current default implementations of co-receptor prediction algorithms are inadequate for predicting HIV X4 co-receptor usage in clinical samples, particularly those X4 phenotypes with low CXCR4 RLU signals. Significant improvements can be made to genotypic predictors, including training on clinical samples, using additional data to improve predictions and optimizing cutoffs and increasing genotype sensitivity.

(C) 2007 Lippincott Williams & Wilkins, Inc.



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Access Level:

Internal

Correlation

MPG Unit:

Max-Planck-Institut für Informatik



MPG Subunit:

Computational Biology and Applied Algorithmics

Audience:

Expert

Appearance:

MPII WWW Server, MPII FTP Server, MPG publications list, university publications list, working group publication list, Fachbeirat, VG Wort


BibTeX Entry:

@ARTICLE{LowDong2007,
AUTHOR = {Low, Andrew J. and Dong, Winnie and Chan, Dennison and Sing, Tobias and Swanstrom, Ronald and Jensen, Mark and Pillai, Satish and Good, Benjamin and Harrigan, P. Richard},
TITLE = {Current {V3} genotyping algorithms are inadequate for predicting {X4} co-receptor usage in clinical isolates},
JOURNAL = {AIDS},
PUBLISHER = {Lippincott Williams & Wilkins},
YEAR = {2007},
NUMBER = {14},
VOLUME = {21},
PAGES = {F19--F26},
MONTH = {September},
ISBN = {0269-9370},
}


Entry last modified by Ruth Schneppen-Christmann, 04/01/2009
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Editor(s)
Anja Becker
Created
02/14/2008 10:58:04 AM
Revisions
2.
1.
0.

Editor(s)
Ruth Schneppen-Christmann
Uwe Brahm
Anja Becker

Edit Dates
01.04.2009 09:48:37
02/28/2008 04:18:31 PM
14.02.2008 11:04:12