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

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States d.f. AIC BIC
1 2 9775.9 9786.7
2 5 9731.3 9758.1
3 10 9729.9 9783.5
Table 4.1 In comparing the GM07535 and CHM genomes, AIC and BIC values for HMM
fits with 1, 2 and 3 states serve as a guide to choose the number of states. In this case, we
choose the model with 2 states.
optical maps represent a population that has 6 known sites each of decreased (1:2) and
elevated (3:2) copy number.
Figure 4.2 shows the results of fitting a 3-state negative binomial HMM to one such
data set. Figure 4.3 summarizes the results from multiple instances of this simulation. For
each simulation, models were fitted using the full data sets as well as smaller subsets. Copy
number changes larger that 1 Mb were detected more or less consistently, while smaller
regions were not. Surprisingly, the results obtained from the smaller data sets were not
much different, except in a couple of runs which had more false positives. Presumably, these
details will vary depending on the size of the genome and the number and magnitude of the
copy number alterations.
Example: GM07535 and CHM: We next considered optical map data from two human
genomes, GM07535 and CHM (Section 1.2), restricting our attention to alignments to
the first 6 chromosomes. 23424 GM07535 and 43502 CHM optical maps aligned to these
chromosomes. Alignments of CHM maps were used as the normalizing genome to detect relative
copy number changes in GM07535. Both genomes are believed to be “normal”, so not
much variation is expected. AIC and BIC values given in Table 4.1 provide some guidance
in selecting an appropriate number of states, and a model with 2 states seems appropriate.
Some regions of mild copy number differences are indicated by the graph of posterior probabilities
in Figure 4.4. The reason for the differences is not clear, but could in part reflect
heterozygous differences in GM07535.