AN ALGORITHM-BASED ON GRAPH-THEORY FOR THE ASSEMBLY OF CONTIGS IN PHYSICAL MAPPING OF DNA

An algorithm is described for mapping DNA contigs based on an interval graph (IG) representation. In general terms, the input to the algorit hm is a set of binary overlapping relations among finite intervals spr ead along a real line, from which the algorithm generates sets of orde red overlapping fragments spanning that line. The implications of a mo re general case of the IG, called a probe interval graph (PIG), in whi ch only a subset of cosmids are used as probes, are also discussed. In the specific case of cosmids hybridizing to regions of a YAC, the alg orithm takes cross-hybridization information using the cosmids as prob es, and orders them along the YAC; if gaps exist due to insufficient c overage of cosmid contigs along the length of the YAC, repetitive use of the algorithm generates sets of ordered overlapping fragments. Both the IG and the PIG can expose problems caused by false overlaps, such as hybridizations due to repetitive elements. The algorithm, has been coded in C; CPU time is essentially linear with respect to the number of cosmids analyzed. Results are presented for the application of a P IG to cosmid contig assembly along a human chromosome 13-specific YAC. An alignment of 67 cosmids spanning a YAC took 0.28 seconds of CPU ti me on a Convex 220 computer.