A statistical approach for array CGH data analysis.
BACKGROUND
Microarray-CGH experiments are used to detect and map chromosomal imbalances, by hybridizing targets of genomic DNA from a test and a reference sample to sequences immobilized on a slide. These probes are genomic DNA sequences (BACs) that are mapped on the genome. The signal has a spatial coherence that can be handled by specific statistical tools. Segmentation methods seem to be a natural framework for this purpose. A CGH profile can be viewed as a succession of segments that represent homogeneous regions in the genome whose BACs share the same relative copy number on average. We model a CGH profile by a random Gaussian process whose distribution parameters are affected by abrupt changes at unknown coordinates. Two major problems arise: to determine which parameters are affected by the abrupt changes (the mean and the variance, or the mean only), and the selection of the number of segments in the profile.


RESULTS
We demonstrate that existing methods for estimating the number of segments are not well adapted in the case of array CGH data, and we propose an adaptive criterion that detects previously mapped chromosomal aberrations. The performances of this method are discussed based on simulations and publicly available data sets. Then we discuss the choice of modeling for array CGH data and show that the model with a homogeneous variance is adapted to this context.


CONCLUSIONS
Array CGH data analysis is an emerging field that needs appropriate statistical tools. Process segmentation and model selection provide a theoretical framework that allows precise biological interpretations. Adaptive methods for model selection give promising results concerning the estimation of the number of altered regions on the genome.
Picard
Franck
F
Institut National Agronomique Paris-Grignon, UMR INAPG/ENGREF/INRA MIA 518, Paris, France. picard@inapg.fr
Robin
Stephane
S
Lavielle
Marc
M
Vaisse
Christian
C
Daudin
Jean-Jacques
JJ
D000465:Algorithms; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D022202:Chromosomes, Artificial, Bacterial / Q000378:metabolism; D019295:Computational Biology / Q000379:methods*; D003196:Computer Graphics; D003198:Computer Simulation; D004247:DNA / Q000235:genetics; D003627:Data Interpretation, Statistical; D003628:Database Management Systems; D018628:Gene Dosage; D020869:Gene Expression Profiling; D005819:Genetic Markers; D016678:Genome; D015894:Genome, Human; D006801:Humans; D008957:Models, Genetic; D015233:Models, Statistical; D016011:Normal Distribution; D009690:Nucleic Acid Conformation; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D015345:Oligonucleotide Probes; D012984:Software; D014584:User-Computer Interface
D005819:Genetic Markers; D015345:Oligonucleotide Probes; D004247:DNA