Evolution of a computer program for classifying protein segments as transmembrane domains using genetic programming.

The recently-developed genetic programming paradigm is used to evolve a computer program to classify a given protein segment as being a transmembrane domain or non-transmembrane area of the protein. Genetic programming starts with a primordial ooze of randomly generated computer programs composed of available programmatic ingredients and then genetically breeds the population of programs using the Darwinian principle of survival of the fittest and an analog of the naturally occurring genetic operation of crossover (sexual recombination). Automatic function definition enables genetic programming to dynamically create subroutines dynamically during the run. Genetic programming is given a training set of differently-sized protein segments and their correct classification (but no biochemical knowledge, such as hydrophobicity values). Correlation is used as the fitness measure to drive the evolutionary process. The best genetically-evolved program achieves an out-of-sample correlation of 0.968 and an out-of-sample error rate of 1.6%. This error rate is better than that reported for four other algorithms reported at the First International Conference on Intelligent Systems for Molecular Biology. Our genetically evolved program is an instance of an algorithm discovered by an automated learning paradigm that is superior to that written by human investigators.