Figure 2.

Schematic representation of CESAR. The Hidden-Markov-Model consists of states that emit the up- and downstream intronic bases, the splice sites and the exon body in between. The exon body consists of states that match entire codons with emission probabilities reflecting the similarity to the codon in the reference exon (47), states that emit partial 1 or 2 bp codons that represent frameshifting deletions, states that insert any of the 61 non-stop codons, and nucleotide insertion states that insert in-frame stop codons or insert frameshifts. Codon deletions are modeled by transitions that skip between 1 and 10 codon units (blue transitions; only 1 to 3 codon deletions are illustrated here for clarity). The non-emitting (silent) black-circle states allow deleting more than 10 successive codons, similar to delete states in a profile HMM (46). All transitions representing exon-inactivating mutations (splice site mutations or frameshifting indels) are shown in red, transitions to codon insertion states are green and transitions that loop in insert states are black. The grey transitions are not free parameters but are fixed by the constraint that the sum of all out-going transition probabilities of a state must be 1.