Finding recurrent copy number alterations preserving within-sample homogeneity

Sandro Morganella, Stefano Maria Pagnotta, Michele Ceccarelli

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Motivation: Copy number alterations (CNAs) represent an important component of genetic variation and play a significant role in many human diseases. Development of array comparative genomic hybridization (aCGH) technology has made it possible to identify CNAs. Identification of recurrent CNAs represents the first fundamental step to provide a list of genomic regions which form the basis for further biological investigations. The main problem in recurrent CNAs discovery is related to the need to distinguish between functional changes and random events without pathological relevance. Within-sample homogeneity represents a common feature of copy number profile in cancer, so it can be used as additional source of information to increase the accuracy of the results. Although several algorithms aimed at the identification of recurrent CNAs have been proposed, no attempt of a comprehensive comparison of different approaches has yet been published. Results: We propose a new approach, called Genomic Analysis of Important Alterations (GAIA), to find recurrent CNAs where a statistical hypothesis framework is extended to take into account within-sample homogeneity. Statistical significance and withinsample homogeneity are combined into an iterative procedure to extract the regions that likely are involved in functional changes. Results show that GAIA represents a valid alternative to other proposed approaches. In addition, we perform an accurate comparison by using two real aCGH datasets and a carefully planned simulation study.

Original languageEnglish
Article numberbtr488
Pages (from-to)2949-2956
Number of pages8
JournalBioinformatics
Volume27
Issue number21
DOIs
Publication statusPublished - 1 Nov 2011
Externally publishedYes

Fingerprint

Comparative Genomic Hybridization
Homogeneity
Genomics
Comparative Genomics
Technology
Neoplasms
Genetic Variation
Statistical Significance
Iterative Procedure
Cancer
Likely
Simulation Study
Valid
Alternatives
Datasets

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Computational Theory and Mathematics
  • Computer Science Applications
  • Computational Mathematics
  • Statistics and Probability
  • Medicine(all)

Cite this

Finding recurrent copy number alterations preserving within-sample homogeneity. / Morganella, Sandro; Pagnotta, Stefano Maria; Ceccarelli, Michele.

In: Bioinformatics, Vol. 27, No. 21, btr488, 01.11.2011, p. 2949-2956.

Research output: Contribution to journalArticle

Morganella, Sandro ; Pagnotta, Stefano Maria ; Ceccarelli, Michele. / Finding recurrent copy number alterations preserving within-sample homogeneity. In: Bioinformatics. 2011 ; Vol. 27, No. 21. pp. 2949-2956.
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