Statistics in Biosciences

, Volume 2, Issue 2, pp 120–136

Assessing Population Level Genetic Instability via Moving Average

  • Samuel McDaniel
  • Jessica Minnier
  • Rebecca A. Betensky
  • Gayatry Mohapatra
  • Yiping Shen
  • James F. Gusella
  • David N. Louis
  • Tianxi Cai
Article

Abstract

Tumoral tissues tend to generally exhibit aberrations in DNA copy number that are associated with the development and progression of cancer. Genotyping methods such as array-based comparative genomic hybridization (aCGH) provide means to identify copy number variation across the entire genome. To address some of the shortfalls of existing methods of DNA copy number data analysis, including strong model assumptions, lack of accounting for sampling variability of estimators, and the assumption that clones are independent, we propose a simple graphical approach to assess population-level genetic alterations over the entire genome based on moving average. Furthermore, existing methods primarily focus on segmentation and do not examine the association of covariates with genetic instability. In our methods, covariates are incorporated through a possibly mis-specified working model and sampling variabilities of estimators are approximated using a resampling method that is based on perturbing observed processes. Our proposal, which is applicable to partial, entire or multiple chromosomes, is illustrated through application to aCGH studies of two brain tumor types, meningioma and glioma.

Keywords

aCGH data Moving average Perturbation method Gaussian process Genomic data 

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Copyright information

© International Chinese Statistical Association 2010

Authors and Affiliations

  • Samuel McDaniel
    • 1
  • Jessica Minnier
    • 2
  • Rebecca A. Betensky
    • 2
  • Gayatry Mohapatra
    • 3
  • Yiping Shen
    • 4
  • James F. Gusella
    • 4
  • David N. Louis
    • 3
  • Tianxi Cai
    • 2
  1. 1.Department of MathematicsThe University of the West IndiesMonaJamaica
  2. 2.Department of BiostatisticsHarvard UniversityBostonUSA
  3. 3.Molecular Neuro-Oncology and Pathology LaboratoriesMassachusetts General HospitalCharlestownUSA
  4. 4.Center for Human Genetic ResearchMassachusetts General HospitalBostonUSA

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