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OJBTM

 Online Journal of Bioinformatics  

Volume 11 (2): 224-244, 2010


Analysis of array CGH data for the detection of single-cell chromosomal imbalances

 

Michele Ampe1 (MSc) , Geert Verbeke1 (PhD), Evelyne Vanneste2(MSc), Joris Robert Vermeesch2(PhD)

 

1 Interuniversity Institute for Biostatistics and statistical Bioinformatics, Katholieke Universiteit Leuven and Universiteit Hasselt and, 2Centre for Human Genetics (CME), Katholieke Universiteit Leuven, Belgium

 

ABSTRACT

 

Ampe M, Verbeke G, Vanneste E, Vermeesch JR., Analysis of array CGH data for the detection of single-cell chromosomal imbalances, Online J Bioinformatics, 11 (2): 224-244, 2010. Array comparative  genomic hybridization (array CGH) can be used to detect genome-wide changes in the chromosomal copy number in single cells. Single cell array CGH has the specific problem of bias introduced by the amplification of the DNA. To increase the resolution and the accuracy of the detection of chromosomal imbalances in single cells, we developed a finite mixture model with a clone-specific correction enabling the detection of chromosomal and segmental aneuploidies. The clone-specific correction is derived from a reference set of normal chromosomes. The detection of aneuploidies is equivalent to searching for regions of successive clones that belong to one of the mixture groups. To obtain these regions, the posterior probabilities of the clones are smoothed by means of a loess smoothing. We tested our methodology on single cells with known aberrations as well as through simulations and could detect both chromosomal and segmental aneuploidies.

 

Key words: Single-cell chromosomal imbalances, array CGH , Finite Mixture, Clone-specific correction


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