Title :
Haplotype Inference Constrained by Plausible Haplotype Data
Author :
Fellows, Michael R. ; Hartman, Tzvika ; Hermelin, Danny ; Landau, Gad M. ; Rosamond, Frances ; Rozenberg, Liat
Author_Institution :
Charles Darwin Univ., Darwin, NT, Australia
Abstract :
The haplotype inference problem (HIP) asks to find a set of haplotypes which resolve a given set of genotypes. This problem is important in practical fields such as the investigation of diseases or other types of genetic mutations. In order to find the haplotypes which are as close as possible to the real set of haplotypes that comprise the genotypes, two models have been suggested which are by now well-studied: The perfect phylogeny model and the pure parsimony model. All known algorithms up till now for haplotype inference may find haplotypes that are not necessarily plausible, i.e., very rare haplotypes or haplotypes that were never observed in the population. In order to overcome this disadvantage, we study in this paper, a new constrained version of HIP under the above-mentioned models. In this new version, a pool of plausible haplotypes H̃ is given together with the set of genotypes G, and the goal is to find a subset H ⊆ H̃ that resolves G. For constrained perfect phylogeny haplotyping (CPPH), we provide initial insights and polynomial-time algorithms for some restricted cases of the problem. For constrained parsimony haplotyping (CPH), we show that the problem is fixed parameter tractable when parameterized by the size of the solution set of haplotypes.
Keywords :
diseases; genetics; inference mechanisms; medical computing; physiological models; polynomial approximation; constrained parsimony haplotyping; constrained perfect phylogeny haplotyping; diseases; genetic mutations; genotypes; haplotype inference problem; parsimony model; phylogeny model; plausible haplotype data; polynomial-time algorithms; Biological system modeling; Computational biology; Genetics; Inference algorithms; Phylogeny; Haplotyping; parameterized complexity.; perfect phylogeny; polynomial-time algorithms; pure parsimony; Algorithms; Genotype; Haplotypes; Humans; Phylogeny; Polymorphism, Single Nucleotide;
Journal_Title :
Computational Biology and Bioinformatics, IEEE/ACM Transactions on
DOI :
10.1109/TCBB.2010.72