Finding maximum likelihood indel scenarios

Abstract

Given a multiple alignment of orthologous DNA sequences and a phylogenetic tree for these sequences, we investigate the problem of reconstructing the most likely scenario of insertions and deletions capable of explaining the gaps observed in the alignment. This problem, that we called the Indel Maximum Likelihood Problem (IMLP), is an important step toward the reconstruction of ancestral genomics sequences, and is important for studying evolutionary processes and genome function. We solve the IMLP using a new type of tree hidden Markov model whose states correspond to single-based evolutionary scenarios and transitions model dependencies between neighboring columns. The standard Viterbi and Forward-backward algorithms are optimized to produce the most likely ancestral reconstruction and to compute the level of confidence associated to specific regions of the reconstruction. The method is illustrated on a set of 85kb sequences from eight mammals. © Springer-Verlag Berlin Heidelberg 2006.