Reference alignment of SNP microarray signals for copy number analysis of tumors.

Bioinformatics 2009 Feb 3;25(3):315-21. Epub 2008 Dec 3.

Department of Biostatistics, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.

Unlabelled: A new procedure to align single nucleotide polymorphism (SNP) microarray signals for copy number analysis is proposed. For each individual array, this reference alignment procedure (RAP) uses a set of selected markers as internal references to direct the signal alignment. RAP aligns the signals so that each array has a similar signal distribution among its reference markers. An accompanying reference selection algorithm (RSA) uses genotype calls and initial signal intensities to choose two-copy markers as the internal references for each array. After RSA and RAP are applied, each array has a similar distribution of signals of two-copy markers so that across-array signal comparisons are biologically meaningful. An upper bound for a statistical metric of signal misalignment is derived and provides a theoretical basis to choose RSA-RAP over other alignment procedures for copy number analysis of cancers. In our study of acute lymphoblastic leukemia, RSA-RAP gives copy number analysis results that show substantially better concordance with cytogenetics than do two other alignment procedures.

Availability: Documented R code is freely available from www.stjuderesearch.org/depts/biostats/refnorm.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2639073PMC
February 2009
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References

(Supplied by CrossRef)
Model-based analysis of oligonucleotide arrays: model validation, design issues and standard error application
Li et al.
Genome Biol. 2001
Cytogenetics as a diagnostic aid for childhood hematologic disorders: conventional cytogenetic techniques, fluorescence in situ hybridization, and comparative genomic hybridization
Raimondi et al.
1998
Statistical approach to road segmentation
Thomas et al.
J. Transp. Eng. 2003

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