Estimation and assessment of raw copy numbers at the single locus level

H. Bengtsson, R. Irizarry, B. Carvalho, T. P. Speed

Research output: Contribution to journalArticlepeer-review

113 Scopus citations


Motivation: Although copy-number aberrations are known to contribute to the diversity of the human DNA and cause various diseases, many aberrations and their phenotypes are still to be explored. The recent development of single-nucleotide polymorphism (SNP) arrays provides researchers with tools for calling genotypes and identifying chromosomal aberrations at an order-of-magnitude greater resolution than possible a few years ago. The fundamental problem in array-based copy-number (CN) analysis is to obtain CN estimates at a single-locus resolution with high accuracy and precision such that downstream segmentation methods are more likely to succeed. Results: We propose a preprocessing method for estimating raw CNs from Affymetrix SNP arrays. Its core utilizes a multichip probe-level model analogous to that for high-density oligonucleotide expression arrays. We extend this model by adding an adjustment for sequence-specific allelic imbalances such as cross-hybridization between allele A and allele B probes. We focus on total CN estimates, which allows us to further constrain the probe-level model to increase the signal-to-noise ratio of CN estimates. Further improvement is obtained by controlling for PCR effects. Each part of the model is fitted robustly. The performance is assessed by quantifying how well raw CNs alone differentiate between one and two copies on Chromosome X (ChrX) at a single-locus resolution (27kb) up to a 200kb resolution. The evaluation is done with publicly available HapMap data.

Original languageEnglish (US)
Pages (from-to)759-767
Number of pages9
Issue number6
StatePublished - Mar 2008
Externally publishedYes

ASJC Scopus subject areas

  • Statistics and Probability
  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Computational Theory and Mathematics
  • Computational Mathematics


Dive into the research topics of 'Estimation and assessment of raw copy numbers at the single locus level'. Together they form a unique fingerprint.

Cite this