Title
QColors: an algorithm for conservative viral quasispecies reconstruction from short and non-contiguous next generation sequencing reads.
Abstract
Next generation sequencing technologies have recently been applied to characterize mutational spectra of the heterogeneous population of viral genotypes (known as a quasispecies) within HIV-infected patients. Such information is clinically relevant because minority genetic subpopulations of HIV within patients enable viral escape from selection pressures such as the immune response and antiretroviral therapy. However, methods for quasispecies sequence reconstruction from next generation sequencing reads are not yet widely used and remains an emerging area of research. Furthermore, the majority of research methodology in HIV has focused on 454 sequencing, while many next-generation sequencing platforms used in practice are limited to shorter read lengths relative to 454 sequencing. Little work has been done in determining how best to address the read length limitations of other platforms. The approach described here incorporates graph representations of both read differences and read overlap to conservatively determine the regions of the sequence with sufficient variability to separate quasispecies sequences. Within these tractable regions of quasispecies inference, we use constraint programming to solve for an optimal quasispecies subsequence determination via vertex coloring of the conflict graph, a representation which also lends itself to data with non-contiguous reads such as paired-end sequencing. We demonstrate the utility of the method by applying it to simulations based on actual intra-patient clonal HIV-1 sequencing data.
Year
DOI
Venue
2012
10.3233/ISB-2012-0454
in Silico Biology
Keywords
DocType
Volume
quasispecies sequence,non-contiguous next generation sequencing,read length limitation,next generation sequencing,quasispecies inference,paired-end sequencing,next-generation sequencing platform,conservative viral quasispecies reconstruction,quasispecies sequence reconstruction,read difference,optimal quasispecies,hiv-1 sequencing data,constraint programming,virology,quasispecies,graph coloring,graphs,graph representation,spectrum,genomics,research methodology,microorganisms
Journal
11
Issue
ISSN
Citations 
5-6
1434-3207
7
PageRank 
References 
Authors
0.50
0
5
Name
Order
Citations
PageRank
Austin Huang170.84
Rami Kantor210536.12
allison k delong370.50
Leeann Schreier470.50
Sorin Istrail51415170.40