A comparison of physical mapping algorithms.pdf

BIOINFORMATICS Vol. 19 no. 11 2003, pages 1303–1310 DOI: 10.1093/bioinformatics/btg166 A comparison of physical mapping algorithms based on the maximum likelihood model Jinling Huang ?,? and Suchendra M. Bhandarkar Department of Computer Science, University of Georgia, Athens, Georgia 30602-7404, USA Received on October 22, 2002; revised on January 30, 2003; accepted on February 6, 2003 ABSTRACT Motivation: Physical mapping of chromosomes using the maximum likelihood (ML) model is a problem of high com- putational complexity entailing both discrete optimization to recover the optimal probe order as well as continuous optimization to recover the optimal inter-probe spacings. In this paper, two versions of the genetic algorithm (GA) are proposed, one with heuristic crossover and determinis- tic replacement and the other with heuristic crossover and stochastic replacement, for the physical mapping problem under the maximum likelihood model. The genetic algo- rithms are compared with two other discrete optimization approaches, namely simulated annealing (SA) and large- step Markov chains (LSMC), in terms of solution quality and runtime efficiency. Results: The physical mapping algorithms based on the GA, SA and LSMC have been tested using synthetic datasets and real datasets derived from cosmid libraries of the fungus Neurospora crassa. The GA, especially the version with heuristic crossover and stochastic replace- ment, is shown to consistently outperform the SA-based and LSMC-based physical mapping algorithms in terms of runtime and final solution quality. Experimental results on real datasets and simulated datasets are presented. Further improvements to the GA in the context of phys- ical mapping under the maximum likelihood model are proposed. Availability: The software is available upon request from the first author. Contact: tupistra@ INTRODUCTION Mapping molecular markers on chromosomes is critical for understanding the genetic structure, various functions and ev