RHO - Radiation hybrid ordering

Radiation hybrid (RH) mapping is a somatic cell technique that is used for ordering markers along a chromosome and estimating the physical distances b etween them. With the advent of this mapping technique, analyzing the exper imental data is becoming a challenging and demanding computational task. In this paper we present the software package RHO (radiation hybrid ordering) . The package implements a number of heuristics that attempt to order genom ic markers along a chromosome, given as input the results of an RH experime nt. The heuristics are based on reducing an appropriate optimization proble m to the traveling salesman problem (TSP). The reduced optimization problem is either the nonparametric obligate chromosome breaks (OCBs) or the param etric maximum likelihood estimation (MLE). We tested our package on both si mulated and publicly available RH data. For synthetic RH data, the reconstr ucted markers' permutation is very close to the original permutation, even with fairly high error rates. For real data we used the framework markers' data from the Whitehead Institute maps. For most of the chromosomes (18 out of 23), there is a perfect agreement or nearly perfect agreement (reversal of chromosome armor arms) between our maps and the Whitehead framework map s. For the remaining five chromosomes, our maps improve:on the Whitehead fr amework maps with respect to both optimization criteria, having higher like lihood-and fewer breakpoints. For three chromosomes, the results differ sig nificantly (lod score >1.75), with chromosome 2 having the largest improvem ent (lod score 3.776).