W-Curve Alignments for HIV-1 Genomic Comparisons

• Published in: PloS one Vol. 5; no. 6; p. e10829
• Main Authors: Cork, Douglas J., Lembark, Steven, Tovanabutra, Sodsai, Robb, Merlin L., Kim, Jerome H.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.06.2010; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; AIDS; AIDS vaccines; Algorithms; Alignment; Analysis; Computational Biology/Comparative Sequence Analysis; Computational Biology/Genomics; Computer applications; Computer Science/Information Technology; Cylindrical coordinates; Deoxyribonucleic acid; Diagnostic systems; DNA; DNA, Viral - genetics; Env gene; Fractals; Gap analysis; Gene sequencing; Genes; Genetics and Genomics/Bioinformatics; Genetics and Genomics/Comparative Genomics; Genome, Viral; Genomes; Genomics; HIV; HIV-1 - genetics; Human immunodeficiency virus; Human immunodeficiency virus 1; Immunoglobulins; Infants; Mathematics/Algorithms; Mathematics/Game Theory; Mathematics/Mathematical Computing; Military medicine; Molecular evolution; Multivariate analysis; Nucleotide sequence; Pandemics; Problem solving; Regression analysis; Ribonucleic acid; RNA; RNA, Viral - genetics; Viruses; Visualization (Computer); New York; United States > US; Maryland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0010829

The W-curve was originally developed as a graphical visualization technique for viewing DNA and RNA sequences. Its ability to render features of DNA also makes it suitable for computational studies. Its main advantage in this area is utilizing a single-pass algorithm for comparing the sequences. Avoiding recursion during sequence alignments offers advantages for speed and in-process resources. The graphical technique also allows for multiple models of comparison to be used depending on the nucleotide patterns embedded in similar whole genomic sequences. The W-curve approach allows us to compare large numbers of samples quickly. We are currently tuning the algorithm to accommodate quirks specific to HIV-1 genomic sequences so that it can be used to aid in diagnostic and vaccine efforts. Tracking the molecular evolution of the virus has been greatly hampered by gap associated problems predominantly embedded within the envelope gene of the virus. Gaps and hypermutation of the virus slow conventional string based alignments of the whole genome. This paper describes the W-curve algorithm itself, and how we have adapted it for comparison of similar HIV-1 genomes. A treebuilding method is developed with the W-curve that utilizes a novel Cylindrical Coordinate distance method and gap analysis method. HIV-1 C2-V5 env sequence regions from a Mother/Infant cohort study are used in the comparison. The output distance matrix and neighbor results produced by the W-curve are functionally equivalent to those from Clustal for C2-V5 sequences in the mother/infant pairs infected with CRF01_AE. Significant potential exists for utilizing this method in place of conventional string based alignment of HIV-1 genomes, such as Clustal X. With W-curve heuristic alignment, it may be possible to obtain clinically useful results in a short time-short enough to affect clinical choices for acute treatment. A description of the W-curve generation process, including a comparison technique of aligning extremes of the curves to effectively phase-shift them past the HIV-1 gap problem, is presented. Besides yielding similar neighbor-joining phenogram topologies, most Mother and Infant C2-V5 sequences in the cohort pairs geometrically map closest to each other, indicating that W-curve heuristics overcame any gap problem.