The use of simulated annealing in chromosome reconstruction experiments based on binary scoring.

We present a method of combinatorial optimization, simulated annealing, to order clones in a library with respect to their position along a chromosome. This ordering method relies on scoring each clone for the presence or absence of specific target sequences, thereby assigning a digital signature to each clone. Specifically, we consider the hybridization of oligonucleotide probes to a clone to constitute the signature. In that the degree of clonal overlap is reflected in the similarity of their signatures, it is possible to construct maps based on the minimization of the differences in signatures across a reconstructed chromosome. Our simulations show that with as few as 30 probes and a clonal density of 4.5 genome equivalents, it is possible to assemble a small eukaryotic chromosome into 33 contiguous blocks of clones (contigs). With higher clonal densities and more probes, this number can be reduced to less than 5 contigs per chromosome.