Reducing system noise in copy number data using principal components of self-self hybridizations

Lee, Y. H., Ronemus, M., Kendall, J., Lakshmi, B., Leotta, A., Levy, D., Esposito, D., Grubor, V., Ye, K., Wigler, M., Yamrom, B. (January 2012) Reducing system noise in copy number data using principal components of self-self hybridizations. Proceedings of the National Academy of Sciences of the United States of America, 109 (3). E103-E110. ISSN 0027-8424

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URL: http://www.ncbi.nlm.nih.gov/pubmed/22207624
DOI: 10.1073/pnas.1106233109

Abstract

Genomic copy number variation underlies genetic disorders such as autism, schizophrenia, and congenital heart disease. Copy number variations are commonly detected by array based comparative genomic hybridization of sample to reference DNAs, but probe and operational variables combine to create correlated system noise that degrades detection of genetic events. To correct for this we have explored hybridizations in which no genetic signal is expected, namely "self-self" hybridizations (SSH) comparing DNAs from the same genome. We show that SSH trap a variety of correlated system noise present also in sample-reference (test) data. Through singular value decomposition of SSH, we are able to determine the principal components (PCs) of this noise. The PCs themselves offer deep insights into the sources of noise, and facilitate detection of artifacts. We present evidence that linear and piecewise linear correction of test data with the PCs does not introduce detectable spurious signal, yet improves signal-to-noise metrics, reduces false positives, and facilitates copy number determination.

Item Type: Paper
Uncontrolled Keywords: comparative genomic hybridization copy number variation principal component analysis singular value decomposition array-cgh data human genome structural variation spectrum disorders de-novo evolution dna normalization autism microarrays
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > copy number variants
CSHL Authors:
Communities: CSHL Cancer Center Shared Resources > Instrumentation Service
CSHL labs > Levy lab
CSHL labs > Wigler lab
CSHL Cancer Center Program > Cancer Genetics
Depositing User: Matt Covey
Date: January 2012
Date Deposited: 30 Jan 2013 17:27
Last Modified: 02 Jan 2018 17:09
PMCID: PMC3271883
Related URLs:
URI: http://repository.cshl.edu/id/eprint/26990

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