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

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Software: The SOMA software suite can be used to perform restriction map alignments.
As in sequence alignment, one is often interested in sub-optimal alignments as well, i.e. highscoring
alignments in addition to the top-scoring one. SOMA is able to find such alignments.
Genspect can be used to visualize alignments reported by SOMA. Figure 1.5 shows a typical
visualization of optical map alignments.
Assembly
The assembly problem can be viewed as a multiple alignment problem, with an additional
step of producing an inferred consensus map. The most successful optical map assembly software
to date is Gentig, based on ideas described in Anantharaman et al. (1997) (for clones)
and Anantharaman et al. (1999) (for genomic DNA). Briefly, they develop a Bayesian approach
where a prior model for the unknown restriction map and a conditional distribution
for optical maps given the true map are used to derive the posterior density for an hypothesized
map. The inferred restriction map is, in principle, the one that maximizes this posterior
density. Due to the complexities of the problem, a complete search is infeasible, and various
heuristics are employed to enable an efficient implementation. We have little to add on the
assembly problem, and refer the reader to the original papers for further details. Gentig
results can also be visualized using Genspect, as shown in Figure 1.6.
1.3.5 Example (continued)
The goal of an optical mapping project is to infer the underlying restriction map of the
genome being studied. For small genomes, Gentig serves this purpose well. However, for
large genomes such as GM07535 and CHM (Table 1.1), the sizes of the data sets exceeds its
capacity, and new algorithms are required. Fortunately, additional information is available
for these data sets in the form of an in silico reference map, derived from the human genome
sequence by locating instances of the SwaI recognition pattern. The genomes being studied
are largely similar to this reference, so we are primarily interested in how their restriction
maps differ from the reference.