Human Immunodeficiency Virus Reverse Transcriptase and Protease Sequence Database: an expanded data model integrating natural language text and sequence analysis programs

Abstract

The HIV Reverse Transcriptase and Protease Sequence Database is an on-line relational database that catalogs evolutionary and drug-related sequence variation in the human immunodeficiency virus (HIV) reverse transcriptase (RT) and protease enzymes, the molecular targets of anti-HIV therapy (http://hivdb.stanford.edu). The database contains a compilation of nearly all published HIV RT and protease sequences, including submissions from International Collaboration databases and sequences published in journal articles. Sequences are linked to data about the source of the sequence sample and the antiretroviral drug treatment history of the individual from whom the isolate was obtained. During the past year 3500 sequences have been added and the data model has been expanded to include drug susceptibility data on sequenced isolates. Database content has also been integrated with didactic text and the output of two sequence analysis programs.

Figure 1

Protease mutations and their relationship to protease inhibitor drug susceptibilities. Drug names are shown at the top of the columns. Amino acid positions are shown at the left of each row. NFV, nelfinavir; SQV, saquinavir; IDV, indinavir; RTV, ritonavir; APV, amprenavir. Red rectangles denote primary resistance mutations. Yellow rectangles denote mutations that contribute to resistance when present with other mutations. Pale yellow rectangles represent mutations that are accessory resistance mutations which also occur as polymorphisms in untreated individuals. Rectangles containing a question mark imply that the relationship between the mutation and drug resistance has not been fully defined. Rectangles containing a star imply that the mutation causes hypersusceptibility to the drug shown at the top of the column. Each rectangle is hyperlinked to a page containing the four types of data shown in the top right box that link mutation and drug. An example of one of these types of data (e.g. SQV susceptibilities of laboratory isolates containing G48V) is shown in the bottom right box.

Figure 2

Composite sequence alignment. This is one of the methods for viewing the results of queries. This query retrieved sequences from HIV-1 subtype B patients receiving nelfinavir as their sole protease inhibitor. The page header shows the query parameters and the numbers of references, patients and isolates returned by the query. The figure legend shows whether the user wished to view the absolute number of mutations at each position and whether the user wished to ignore rare occurrences that were observed in only one sequence. The first line in that summary shows the numbered consensus sequence. The second line contains the total number of isolates in the data set at each position. The remaining lines show the frequency of variation at each position in the sequence data set. If this composite alignment is compared to the composite alignment of protease sequences from untreated patients, one would observe that the changes at codons 30, 46, 73, 88 and 90 occurred only in isolates from patients who had received nelfinavir and that changes at codons 36 and 71 were present in both alignments but occurred more commonly in isolates from patients receiving nelfinavir.