title: Accuracy assessment of diploid consensus sequences.
abstract: If the origins of fragments are known in genome sequencing projects, it is straightforward to reconstruct diploid consensus sequences. In reality, however, this is not true. Although there are proposed methods to reconstruct haplotypes from genome sequencing projects, an accuracy assessment is required to evaluate the confidence of the estimated diploid consensus sequences. In this paper, we define the confidence score of diploid consensus sequences. It requires the calculation of the likelihood of an assembly. To calculate the likelihood, we propose a linear time algorithm with respect to the number of polymorphic sites. The likelihood calculation and confidence score are used for further improvements of haplotype estimation in two directions. One direction is that low-scored phases are disconnected. The other direction is that, instead of using nominal frequency 1/2, the haplotype frequency is estimated to reflect the actual contribution of each haplotype. Our method was evaluated on the simulated data whose polymorphism rate (1.2 percent) was based on Ciona intestinalis. As a result, the high accuracy of our algorithm was indicated: The true positive rate of the haplotype estimation was greater than 97 percent.
authors.affiliation: Department of Computer Science, University of Southern California, Los Angeles 90089, USA. jonghkim@usc.edu
authors.forename: Jong Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Michael S
authors.initials: MS
authors.lastname: Waterman
authors.forename: Lei M
authors.initials: LM
authors.lastname: Li
mesh_terms: D000465:Algorithms; D000818:Animals; D002938:Ciona intestinalis / Q000235:genetics; D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D016384:Consensus Sequence / Q000235:genetics*; D004171:Diploidy; D005787:Gene Frequency; D006239:Haplotypes; D016013:Likelihood Functions; D008390:Markov Chains; D015233:Models, Statistical; D011110:Polymorphism, Genetic; D011336:Probability; D017422:Sequence Analysis, DNA / Q000379:methods / Q000706:statistics & numerical data*