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


BACKGROUND
Documented R code is freely available from www.stjuderesearch.org/depts/biostats/refnorm.
Pounds
Stan
S
Department of Biostatistics, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA. stanley.pounds@stjude.org
Cheng
Cheng
C
Mullighan
Charles
C
Raimondi
Susana C
SC
Shurtleff
Sheila
S
Downing
James R
JR
D000465:Algorithms; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D002869:Chromosome Aberrations; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods*; D018628:Gene Dosage; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics; D016415:Sequence Alignment / Q000379:methods
D014408:Biomarkers, Tumor