title: Probabilistic model based error correction in a set of various mutant sequences analyzed by next-generation sequencing.
abstract: To analyze the evolutionary dynamics of a mutant population in an evolutionary experiment, it is necessary to sequence a vast number of mutants by high-throughput (next-generation) sequencing technologies, which enable rapid and parallel analysis of multikilobase sequences. However, the observed sequences include many errors of base call. Therefore, if next-generation sequencing is applied to analysis of a heterogeneous population of various mutant sequences, it is necessary to discriminate between true bases as point mutations and errors of base call in the observed sequences, and to subject the sequences to error-correction processes. To address this issue, we have developed a novel method of error correction based on the Potts model and a maximum a posteriori probability (MAP) estimate of its parameters corresponding to the "true sequences". Our method of error correction utilizes (1) the "quality scores" which are assigned to individual bases in the observed sequences and (2) the neighborhood relationship among the observed sequences mapped in sequence space. The computer experiments of error correction of artificially generated sequences supported the effectiveness of our method, showing that 50-90% of errors were removed. Interestingly, this method is analogous to a probabilistic model based method of image restoration developed in the field of information engineering.
authors.affiliation: Exploratory Research for Advanced Technology, Japan Science and Technology Agency, Yamadaoka 1-5, Suita, Osaka, Japan.
authors.forename: Takuyo
authors.initials: T
authors.lastname: Aita
authors.forename: Norikazu
authors.initials: N
authors.lastname: Ichihashi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yomo
mesh_terms: D000465:Algorithms; D004247:DNA / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D015233:Models, Statistical; D009154:Mutation; D017422:Sequence Analysis, DNA
chemical_list: D004247:DNA
keywords: Base call error; Image restoration; Quality score; Quasispecies; SMRT; Sequence analysis