Affiliations: Dependable and High-performance Computing, Research
Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba,
Meguro-ku, Tokyo 153-8904, Japan | Intelligent and Cooperative System, Research Center
for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba,
Meguro-ku, Tokyo 153-8904, Japan | Genome Science Division, Research Center for Advanced
Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo
153-8904, Japan | Affymetrix, Inc., 3380 Central Expressway, Santa
Clara, CA 95051, USA | CREST, Japan Science and Technology Agency, 4-1-8
Honchou Kawaguchi, Saitama Japan
Abstract: Genomic copy number change is one of the important phenomenon
observed in cancer and other genetic disorders. Recently oligonucleotide
microarrays have been used to analyze changes in the copy number. Although high
density microarrays provide genome wide useful data on copy number, they are
often associated with substantial amount of experimental noise that could
affect the performance of the analyses. We used the high density oligonucleotide genotyping microarrays in
our experiments that uses redundant probe tiling approach for individual SNPs.
We found that the noise in the genotyping microarray data is associated with
several experimental steps during target preparation and devised an algorithm
that takes into account those experimental parameters. Additionally, defective
probes that do not hybridize well to the target and therefore could not be
modified inherently were detected and omitted automatically by using the
algorithm. When we applied the algorithm to actual datasets, we could reduce
the noise substantially without compressing the dynamic range. Additionally,
combinatorial use of our noise reduction algorithm and conventional breakpoint
detection algorithm successfully detected a microamplification of c-myc which
was overlooked in the raw data. The algorithm described here is freely available with the software
upon request to all non-profit researchers.
