Joint estimation of DNA copy number from multiple platforms.
BACKGROUND
DNA copy number variants (CNVs) are gains and losses of segments of chromosomes, and comprise an important class of genetic variation. Recently, various microarray hybridization-based techniques have been developed for high-throughput measurement of DNA copy number. In many studies, multiple technical platforms or different versions of the same platform were used to interrogate the same samples; and it became necessary to pool information across these multiple sources to derive a consensus molecular profile for each sample. An integrated analysis is expected to maximize resolution and accuracy, yet currently there is no well-formulated statistical method to address the between-platform differences in probe coverage, assay methods, sensitivity and analytical complexity.


RESULTS
The conventional approach is to apply one of the CNV detection ('segmentation') algorithms to search for DNA segments of altered signal intensity. The results from multiple platforms are combined after segmentation. Here we propose a new method, Multi-Platform Circular Binary Segmentation (MPCBS), which pools statistical evidence across platforms during segmentation, and does not require pre-standardization of different data sources. It involves a weighted sum of t-statistics, which arises naturally from the generalized log-likelihood ratio of a multi-platform model. We show by comparing the integrated analysis of Affymetrix and Illumina SNP array data with Agilent and fosmid clone end-sequencing results on eight HapMap samples that MPCBS achieves improved spatial resolution, detection power and provides a natural consensus across platforms. We also apply the new method to analyze multi-platform data for tumor samples.


BACKGROUND
The R package for MPCBS is registered on R-Forge (http://r-forge.r-project.org/) under project name MPCBS.


BACKGROUND
Supplementary data are available at Bioinformatics online.
Zhang
Nancy R
NR
Department of Statistics, Stanford University, Stanford, CA, USA. nzhang@stanford.edu
Senbabaoglu
Yasin
Y
Li
Jun Z
JZ
D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D004247:DNA / Q000737:chemistry*; D056915:DNA Copy Number Variations; D030541:Databases, Genetic; D020869:Gene Expression Profiling / Q000379:methods; D014644:Genetic Variation
D004247:DNA