A probe-density-based analysis method for array CGH data: Simulation, normalization and centralization

Hung I.Harry Chen, Fang Han Hsu, Yuan Jiang, Mong Hsun Tsai, Pan Chyr Yang, Paul S. Meltzer, Eric Y. Chuang, Yidong Chen

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Motivation: Genomic instability is one of the fundamental factors in tumorigenesis and tumor progression. Many studies have shown that copy-number abnormalities at the DNA level are important in the pathogenesis of cancer. Array comparative genomic hybridization (aCGH), developed based on expression microarray technology, can reveal the chromosomal aberrations in segmental copies at a high resolution. However, due to the nature of aCGH, many standard expression data processing tools, such as data normalization, often fail to yield satisfactory results. Results: We demonstrated a novel aCGH normalization algorithm, which provides an accurate aCGH data normalization by utilizing the dependency of neighboring probe measurements in aCGH experiments. To facilitate the study, we have developed a hidden Markov model (HMM) to simulate a series of aCGH experiments with random DNA copy number alterations that are used to validate the performance of our normalization. In addition, we applied the proposed normalization algorithm to an aCGH study of lung cancer cell lines. By using the proposed algorithm, data quality and the reliability of experimental results are significantly improved, and the distinct patterns of DNA copy number alternations are observed among those lung cancer cell lines.

Original languageEnglish (US)
Pages (from-to)1749-1756
Number of pages8
JournalBioinformatics
Volume24
Issue number16
DOIs
StatePublished - Aug 1 2008
Externally publishedYes

ASJC Scopus subject areas

  • Statistics and Probability
  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Computational Theory and Mathematics
  • Computational Mathematics

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    Chen, H. I. H., Hsu, F. H., Jiang, Y., Tsai, M. H., Yang, P. C., Meltzer, P. S., Chuang, E. Y., & Chen, Y. (2008). A probe-density-based analysis method for array CGH data: Simulation, normalization and centralization. Bioinformatics, 24(16), 1749-1756. https://doi.org/10.1093/bioinformatics/btn321