Two methods for improving performance of an HMM and their application for gene finding.

A hidden Markov model for gene finding consists of submodels for coding regions, splice sites, introns, intergenic regions and possibly more. It is described how to estimate the model as a whole from labeled sequences instead of estimating the individual parts independently from subsequences. It is argued that the standard maximum likelihood estimation criterion is not optimal for training such a model. Instead of maximizing the probability of the DNA sequence, one should maximize the probability of the correct prediction. Such a criterion, called conditional maximum likelihood, is used for the gene finder 'HMM-gene'. A new (approximative) algorithm is described, which finds the most probable prediction summed over all paths yielding the same prediction. We show that these methods contribute significantly to the high performance of HMMgene.