Title
Mutant-bin: unsupervised haplotype estimation of viral population diversity without reference genome.
Abstract
High genetic variability in viral populations plays an important role in disease progression, pathogenesis, and drug resistance. The last few years has seen significant progress in the development of methods for reconstruction of viral populations using data from next-generation sequencing technologies. These methods identify the differences between individual haplotypes by mapping the short reads to a reference genome. Much less has been published about resolving the population structure when a reference genome is lacking or is not well-defined, which severely limits the application of these new technologies to resolve virus population structure. We describe a computational framework, called Mutant-Bin, for clustering individual haplotypes in a viral population and determining their prevalence based on a set of deep sequencing reads. The main advantages of our method are that: (i) it enables determination of the population structure and haplotype frequencies when a reference genome is lacking; (ii) the method is unsupervised-the number of haplotypes does not have to be specified in advance; and (iii) it identifies the polymorphic sites that co-occur in a subset of haplotypes and the frequency with which they appear in the viral population. The method was evaluated on simulated reads with sequencing errors and 454 pyrosequencing reads from HIV samples. Our method clustered a high percentage of haplotypes with low false-positive rates, even at low genetic diversity.
Year
DOI
Venue
2013
10.1089/cmb.2012.0174
JOURNAL OF COMPUTATIONAL BIOLOGY
Keywords
Field
DocType
algorithms,computational molecular biology,next generation sequencing,sequence analysis,viruses
Population,Deep sequencing,Biology,Genetic variability,Haplotype,DNA sequencing,Bioinformatics,Reference genome,Haplotype estimation,Sequence analysis
Journal
Volume
Issue
ISSN
20.0
6
1066-5277
Citations 
PageRank 
References 
4
0.44
14
Authors
4
Name
Order
Citations
PageRank
Shruthi Prabhakara1122.51
Raunaq Malhotra253.17
Raj Acharya334755.42
Mary Poss441.79