1 research outputs found
Detection of recurrent copy number alterations in the genome: taking among-subject heterogeneity seriously
Se adjunta un fichero pdf con los datos de investigaci贸n titulado "Supplementary Material for \Detection of Recurrent Copy
Number Alterations in the Genome: taking among-subject
heterogeneity seriously"Background: Alterations in the number of copies of genomic DNA that are common or recurrent
among diseased individuals are likely to contain disease-critical genes. Unfortunately, defining
common or recurrent copy number alteration (CNA) regions remains a challenge. Moreover, the
heterogeneous nature of many diseases requires that we search for common or recurrent CNA
regions that affect only some subsets of the samples (without knowledge of the regions and subsets
affected), but this is neglected by most methods.
Results: We have developed two methods to define recurrent CNA regions from aCGH data.
Our methods are unique and qualitatively different from existing approaches: they detect regions
over both the complete set of arrays and alterations that are common only to some subsets of the
samples (i.e., alterations that might characterize previously unknown groups); they use probabilities
of alteration as input and return probabilities of being a common region, thus allowing researchers
to modify thresholds as needed; the two parameters of the methods have an immediate,
straightforward, biological interpretation. Using data from previous studies, we show that we can
detect patterns that other methods miss and that researchers can modify, as needed, thresholds of
immediate interpretability and develop custom statistics to answer specific research questions.
Conclusion: These methods represent a qualitative advance in the location of recurrent CNA
regions, highlight the relevance of population heterogeneity for definitions of recurrence, and can
facilitate the clustering of samples with respect to patterns of CNA. Ultimately, the methods
developed can become important tools in the search for genomic regions harboring disease-critical
genesFunding provided by Fundaci贸n de Investigaci贸n M茅dica Mutua
Madrile帽a. Publication charges covered by projects CONSOLIDER:
CSD2007-00050 of the Spanish Ministry of Science and Innovation and by
RTIC COMBIOMED RD07/0067/0014 of the Spanish Health Ministr