Probabilistic Inference of Viral Quasispecies Subject to Recombination
Title | Probabilistic Inference of Viral Quasispecies Subject to Recombination |
Publication Type | Conference Paper |
Year of Publication | 2012 |
Authors | Zagordi, O., Töpfer A., Prabhakaran S., Roth V., Halperin E., & Beerenwinkel N. |
Page(s) | 342-354 |
Other Numbers | 3255 |
Keywords | Hidden Markov model, Molecular sequence analysis, Next-generation sequencing, Sequencing and genotyping technologies, Viral quasispecies |
Abstract | RNA viruses are present in a single host as a population ofdifferent but related strains. This population, shaped by the combinationof genetic change and selection, is called quasispecies. Genetic change isdue to both point mutations and recombination events. We present ajumping hidden Markov model that describes the generation of the viralquasispecies and a method to infer its parameters by analysing nextgeneration sequencing data. The model introduces position-specific probabilitytables over the sequence alphabet to explain the diversity that canbe found in the population at each site. Recombination events are indicatedby a change of state, allowing a single observed read to originatefrom multiple sequences. We present an implementation of the EM algorithmto find maximum likelihood estimates of the model parametersand a method to estimate the distribution of viral strains in the quasispecies.The model is validated on simulated data, showing the advantageof explicitly taking the recombination process into account, and appliedto reads obtained from two experimental HIV samples. |
URL | http://www.icsi.berkeley.edu/pubs/algorithms/ICSI_probabilisticinferenceofviral12.pdf |
Bibliographic Notes | Proceedings of the 16th Annual International Conference on Research in Computational Molecular Biology (RECOMB 2012), Barcelona, Spain, pp.342-354 |
Abbreviated Authors | O. Zagordi, A. Topfer, S. Prabhakaran, V. Roth, E. Halperin, and N. Beerenwinkel |
ICSI Research Group | Algorithms |
ICSI Publication Type | Article in conference proceedings |