Using Cytogenetics Data To Guide the Normalization of SNP Microarray Signals

• Activity Number: 23
• Type: Contributed
• Date/Time: Sunday, August 6, 2006 : 2:00 PM to 3:50 PM
• Sponsor: Biometrics Section
• Author(s): Stanley Pounds*+ and Cheng Cheng and Charles Mullighan and Salil Goorha and Sheila Shurtleff and Susana C. Raimondi and James R. Downing
• Companies: St. Jude Children's Research Hospital and St. Jude Children's Research Hospital and St. Jude Children's Research Hospital and St. Jude Children's Research Hospital and St. Jude Children's Research Hospital and St. Jude Children's Research Hospital and St. Jude Children's Research Hospital
• Keywords: microarray ; SNP ; DNA copy number ; cytogenetics ; normalization ; genomics

Abstract

SNP microarrays simultaneously query genomic DNA at thousands of positions and are used to identify regions of DNA gain or loss in tumor cells. Correct identification of such regions depends on accurately normalizing the array signals. Readily available software implements a median-centering normalization. However, it implicitly requires that the copy number of much of the genome is unaltered; this is not true for several cancers. In some cases, median-centering infers incorrect copy numbers for the entire genome. Therefore, we propose a method that uses cytogenetics data, which identifies microscopic genomic lesions, to guide the normalization of SNP array signals. In our study of 242 pediatric acute lymphoblastic leukemia cases, the proposed method leads to more accurate copy number inferences than does median-centering.