Combfit: A Normalization Method for Array CGH Data

Abstract

The recently developed array-based comparative genomic hybridization (array CGH) technique measures DNA copy number aberrations that occur as causes or consequences of cell diseases such as cancers. Conventional array CGH analysis classifies DNA copy number aberrations into three categories: no significant change, significant gain, and significant loss. However, recent improvements in microarray measurement precision enable more quantitative analysis of copy number aberrations. We propose a method, called comb fitting, that extracts a quantitative interpretation from array CGH data. We also propose modifications that allow us to apply comb fitting to cases featuring heterogeneity of local aberrations in DNA copy numbers. By using comb fitting, we can correct the baseline of the fluorescence ratio data measured by array CGH and simultaneously translate them into the amount of changed copy numbers for each small part of the chromosome, such as 0, ±1, ±2, · · ·. Comb fitting is applicable even when a considerable amount of contamination by normal cells exists and when heterogeneity in the ploidy number cannot be neglected.

Novel risk stratification of patients with neuroblastoma by genomic signature, which is independent of molecular signature

“…The fluorescence ratio for each array CGH spot was normalized and rescaled into estimated copy number aberrations of each clone according to the comb-fit method (Oba et al, 2006; see also Supplementary Figure S2a). Chromosomal events were detected by locally smoothing variations in copy number aberrations of clones on a chromosome and by applying threshold rules (see Supplementary Figure S2a and Supplementary Information for more detail).…”