On the Analysis of Optical Mapping Data - University of Wisconsin ...

5
for microbial and other small genomes. In the early stages of a sequencing project, a genomewide
restriction map provides ordering and orientation information for sequence contigs. In
later stages, optical mapping can be used to validate ordering and orientation, estimate
sequence gap sizes, and identify potential misassemblies. Recently, the focus of optical
mapping has changed in two important ways. First, the ability to automate image processing
and much of the subsequent analysis has made it practical to collect and analyze very large
data sets. This allows the study of large genomes. Second, as more and more high quality
sequence information has become available, the detection of genomic variation has emerged
as a major goal of optical mapping. The construction of restriction maps to aid sequencing is
still important for organisms where sequence information is absent or incomplete. This is a
particularly challenging task for large genomes, with mixed success so far. In this thesis, we
will largely restrict our attention to the case where a high quality reference copy is available.
1.2 Example
Throughout the thesis, we use optical map data recently collected and reported by
Reslewic et al. (unpublished) to illustrate specific ideas. The data were obtained from two human
cell sources. One was a normal diploid male lymphoblastoid cell line GM07535 (Coriell
Cell Repositories, Camden, NJ). The other was a complete hydatidiform mole (CHM), artificially
created to be homozygous (Fan et al., 2002). The restriction enzyme SwaI was used
in both cases. Table 1.1 gives some basic numerical summaries of the two data sets.
Source CHM GM07535
Number of maps 416284 206796
Avg. molecule size (Kb) 436.5 441.9
Avg. fragment size (Kb) 21.3 20.2
Total map mass (Mb) 187386 91915
Approximate coverage 62.1 29.9
Table 1.1 Summary of the CHM and GM07535 data sets