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Author, Editor(s)

Author(s):

Sander, Oliver
Sing, Tobias
Sommer, Ingolf
Low, Andrew J.
Cheung, Peter K.
Harrigan, P. Richard
Lengauer, Thomas
Domingues, Francisco S.

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Not MPG Author(s):

Low, Andrew J.
Cheung, Peter K.
Harrigan, P. Richard

BibTeX cite key*:

Sander2007

Title

Title*:

Structural Descriptors of gp120 V3 Loop for the Prediction of HIV-1 Coreceptor Usage


Sander.pdf (2666.5 KB)

Journal

Journal Title*:

PLoS Computational Biology

Journal's URL:

http://compbiol.plosjournals.org

Download URL
for the article:

http://dx.doi.org/10.1371/journal.pcbi.003005

Language:

English

Publisher

Publisher's
Name:

Public Library of Science

Publisher's URL:


Publisher's
Address:

San Francisco, CA, USA

ISSN:

1553-734X

Vol, No, pp, Date

Volume*:

3

Number:

3

Publishing Date:

2007

Pages*:

555-564

Number of
VG Pages:


Page Start:

555

Page End:

564

Sequence Number:

e58

DOI:

10.1371/journal.pcbi.0030058

Note, Abstract, ©

Note:


(LaTeX) Abstract:

HIV-1 cell entry commonly uses, in addition to CD4, one of the chemokine receptors CCR5 or CXCR4 as coreceptor. Knowledge of coreceptor usage is critical for monitoring disease progression as well as for supporting therapy with the novel drug class of coreceptor antagonists. Predictive methods for inferring coreceptor usage based on the third hypervariable (V3) loop region of the viral gene coding for the envelope protein gp120 can provide these monitoring facilities while avoiding expensive phenotypic tests. All simple heuristics (like the 11/25 rule) as well as statistical learning methods proposed to date predict coreceptor usage based on sequence features of the V3 loop exclusively. Here, we show, based on a recently resolved structure of gp120 with an untruncated V3 loop, that using structural information on the V3 loop in combination with sequence features of V3 variants improves prediction of coreceptor usage. In particular, we propose a distance-based descriptor of the spatial arrangement of physicochemical properties that increases discriminative performance. For a fixed specificity of 0.95, a sensitivity of 0.77 was achieved, improving further to 0.80 when combined with a sequence-based representation using amino acid indicators. This compares favorably with the sensitivities of 0.62 for the traditional 11/25 rule and 0.73 for a prediction based on sequence information as input to a support vector machine (SVM) and constitutes a statistically significant improvement. A detailed analysis and interpretation of structural features important for classification shows the relevance of several specific hydrogen-bond donor sites and aliphatic side chains to coreceptor specificity towards CCR5 or CXCR4. Furthermore, an analysis of side chain orientation of the specificity determining residues suggests a major role of one side of the V3 loop in the selection of the coreceptor. The proposed method constitutes the first approach to an improved prediction of coreceptor usage based on an original integration of structural bioinformatics methods with statistical learning.

URL for the Abstract:

http://compbiol.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pcbi.0030058.eor

Categories,
Keywords:


HyperLinks / References / URLs:


Copyright Message:

Copyright: © 2007 Sander et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Personal Comments:


Download
Access Level:

Public

Correlation

MPG Unit:

Max-Planck-Institut für Informatik



MPG Subunit:

Computational Biology and Applied Algorithmics

Appearance:

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


BibTeX Entry:

@ARTICLE{Sander2007,
AUTHOR = {Sander, Oliver and Sing, Tobias and Sommer, Ingolf and Low, Andrew J. and Cheung, Peter K. and Harrigan, P. Richard and Lengauer, Thomas and Domingues, Francisco S.},
TITLE = {Structural Descriptors of gp120 {V3} Loop for the Prediction of {HIV-1} Coreceptor Usage},
JOURNAL = {PLoS Computational Biology},
PUBLISHER = {Public Library of Science},
YEAR = {2007},
NUMBER = {3},
VOLUME = {3},
PAGES = {555--564},
ADDRESS = {San Francisco, CA, USA},
ISBN = {1553-734X},
DOI = {10.1371/journal.pcbi.0030058},
}


Entry last modified by Uwe Brahm, 02/28/2008
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Editor(s)
Oliver Sander
Created
03/21/2007 04:02:14 PM
Revisions
7.
6.
5.
4.
3.
Editor(s)
Uwe Brahm
Anja Becker
Anja Becker
Christine Kiesel
Christine Kiesel
Edit Dates
02/28/2008 04:19:30 PM
14.02.2008 15:48:52
14.02.2008 15:45:37
01.07.2007 14:40:30
01.07.2007 14:09:54
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