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The electronic form of this document may be cited in the following style:
Human Genome Program, U.S. Department of Energy, DOE Human Genome Program Contractor-Grantee Workshop IV, 1994.

Abstracts scanned from text submitted for November 1994 DOE Human Genome Program Contractor-Grantee Workshop. Inaccuracies have not been corrected.

A Software.Tool to Determine Overlaps Between Clones and Existing Restriction Fragment Maps

T. Mimi Yeh (myeh@llnl.gov), and Tom Slezak
Human Genome Center, L-452, Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, Livermore, California 94550.

The LLNL Human Genome Center currently has over 50% of chromosome 19 covered with high-resolution EcoRI restriction fragment maps. As the number of the restriction fragment maps in our database nears 200, an automatic clone matching software tool is needed to help the chromosome 19 closure effort. Such a tool would have two functions: 1) Given a clone (or a list of clones) find the "best" matches against all the restriction fragment maps within our database, 2) Find pairs of restriction maps that possibly overlap on their ends. This will assist us in the gap closing process by freeing the map builders from tedious manual clone matching and by minimizing human errors as much as possible. We note that with such a large amount of chromosonal real estate covered it is quite likely that there may be multiple candidate "fits" for any given clone. We need to find all likely sites and then use other mapping data (insitu or other hybridization, FISH, statistical overlap, etc.) and human judgement to determine the most likely placement.

We use a sliding window method for the comparison process. A window with the size of the input clone length slides along the current restriction map to perform the comparison between the fragments in the sliding window and the input clone fragment list. The sliding window and the input clone fragment lists are both sorted for an efficient comparison. Scores are calculated based on the comparison of matching results for both end windows or interior windows. (End windows are defined as cases where the input clone would extend one or both ends of the existing map.)

The result scores are presented to the user showing the most likely location(s) for both end-extension to existing maps and placement totally with existing maps. By running the program on lists of end clones of existing maps we can dredge for overlaps that have not yet been determined by other means. A number of parameters can be chosen by the user at run time to set the stringency of the comparison. This tool will see wide use in our closure of chromosome 19 and in high-resolution mapping on other genomic targets.

This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory contract no. W-7405-ENG-48.