This article is available from: http://www.biomedcentral.com/1471-2334/6/44
[Background] Genotypic assays based on DNA sequencing of part or the whole reverse
transcriptase (RT)- and protease (PR)-coding regions of the human immunodeficiency virus type 1
(HIV-1) genome have become part of the routine clinical management of HIV-infected individuals.
However, the results are difficult to interpret due to complex interactions between mutations
found in viral genes.
[Results] DR_SEQAN is a tool to analyze RT and PR sequences. The program output includes a
list containing all of the amino acid changes found in the query sequence in comparison with the
sequence of a wild-type HIV-1 strain. Translation of codons containing nucleotide mixtures can
result in potential ambiguities or heterogeneities in the amino acid sequence. The program
identifies all possible combinations of 2 or 3 amino acids that derive from translation of triplets
containing nucleotide mixtures. In addition, when ambiguities affect codons relevant for drug
resistance, DR_SEQAN allows the user to select the appropriate mutation to be considered by the
program's drug resistance interpretation algorithm. Resistance is predicted using a rule-based
algorithm, whose efficiency and accuracy has been tested with a large set of drug susceptibility data.
Drug resistance predictions given by DR_SEQAN were consistent with phenotypic data and
coherent with predictions provided by other publicly available algorithms. In addition, the program
output provides two tables showing published drug susceptibility data and references for mutations
and combinations of mutations found in the analyzed sequence. These data are retrieved from an
integrated relational database, implemented in Microsoft Access, which includes two sets of nonredundant
core tables (one for combinations of mutations in the PR and the other for combinations
in the RT)
[Conclusion] DR_SEQAN is an easy to use off-line application that provides expert advice on HIV
genotypic resistance interpretation. It is coded in Visual Basic for use in PC/Windows-based
platforms. The program is freely available under the General Public License. The program (including
the integrated database), documentation and a sample sequence can be downloaded from http://
www2.cbm.uam.es:8080/lmenendez/DR_SEQAN.zip
This work has been supported in part by the Fundación para la Investigación
y Prevención del SIDA en España (FIPSE), through grants 36200/01 and
36460/05. An institutional grant of Fundación Ramón Areces to Centro de
Biología Molecular "Severo Ochoa" is also acknowledged.
Peer reviewed