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

Bioinformatics. 2009 Feb 1;25(3):315-21. doi: 10.1093/bioinformatics/btn624. Epub 2008 Dec 3.


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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics
  • Chromosome Aberrations*
  • Cluster Analysis
  • Computational Biology / methods*
  • Gene Dosage
  • Humans
  • Neoplasms / genetics*
  • Oligonucleotide Array Sequence Analysis / methods*
  • Polymorphism, Single Nucleotide / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Sequence Alignment / methods


  • Biomarkers, Tumor