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le jeudi 02 décembre à 11:00

Guillem Rigaill (AgroParisTech, Paris)

Salle de formation du PRABI

par Vincent Daubin - 2 décembre 2010

Statistical and algorithmic developments for the analysis of SNP/CGH arrays,
with application to breast cancer data.

Basal-like breast cancers are among the breast cancers with the poorest
prognoses and patients do not benefit from any targeted therapy yet. We
aim to identify the deregulated signaling pathways using genomic,
transcriptomic and proteomic (RPPA) data in order to identify
therapeutic targets. In this talk, I will focus on the analysis of SNP
and CGH data. More specifically, I will discuss several statistical and
algorithmic challenges directly related to their statistical analysis.

1) Normalisation
One important issue when analyzing SNP profiles is their normalisation.
Indeed, especially with tumour profiles, it cannot be assumed that most
of the genome is normal and it has been shown that not taking these
genomic alterations into account while normalising leads to
over-correction. We propose a method to estimate the signal (or copy number)
and correct technical artefacts simultaneously.

2) Exact and Fast segmentation
A CGH profile can be viewed as a succession of segments representing
regions in the genome that share the same DNA copy number.
Multiple-change-point detection methods constitute a natural framework
for their analysis and the detection of breakpoints. However, recovering
the optimal position of the breakpoints is not an easy task, especially
for large SNP profiles such as Affymetrix SNP 6.0. We propose an
algorithm to recover quickly the best segmentation (the maximum
likelihood estimate).

3) Assessing the quality of a segmentation
Assessing the quality of a segmentation and in particular the confidence
we have
in a particular breakpoint is a difficult problem. We propose algorithms
and statistical
methods to assess and take into account the quality of possible
segmentations.