Journal Article

Joint estimation of copy number variation and reference intensities on multiple DNA arrays using GADA

Roger Pique-Regi, Antonio Ortega and Shahab Asgharzadeh

in Bioinformatics

Volume 25, issue 10, pages 1223-1230
Published in print May 2009 | ISSN: 1367-4803
Published online March 2009 | e-ISSN: 1460-2059 | DOI: http://dx.doi.org/10.1093/bioinformatics/btp119
Joint estimation of copy number variation and reference intensities on multiple DNA arrays using GADA

More Like This

Show all results sharing this subject:

  • Bioinformatics and Computational Biology

GO

Show Summary Details

Preview

Motivation: The complexity of a large number of recently discovered copy number polymorphisms is much higher than initially thought, thus making it more difficult to detect them in the presence of significant measurement noise. In this scenario, separate normalization and segmentation is prone to lead to many false detections of changes in copy number. New approaches capable of jointly modeling the copy number and the non-copy number (noise) hybridization effects across multiple samples will potentially lead to more accurate results.

Methods: In this article, the genome alteration detection analysis (GADA) approach introduced in our previous work is extended to a multiple sample model. The copy number component is independent for each sample and uses a sparse Bayesian prior, while the reference hybridization level is not necessarily sparse but identical on all samples. The expectation maximization (EM) algorithm used to fit the model iteratively determines whether the observed hybridization levels are more likely due to a copy number variation or to a shared hybridization bias.

Results: The new proposed approach is compared with the currently used strategy of separate normalization followed by independent segmentation of each array. Real microarray data obtained from HapMap samples are randomly partitioned to create different reference sets. Using the new approach, copy number and reference intensity estimates are significantly less variable if the reference set changes; and a higher consistency on copy numbers detected within HapMap family trios is obtained. Finally, the running time to fit the model grows linearly in the number samples and probes.

Availability:http://biron.usc.edu/∼piquereg/GADA

Contact: rpique@ieee.org; shahab@chla.usc.edu

Supplementary information:Supplementary data are available at Bioinformatics online.

Journal Article.  5818 words.  Illustrated.

Subjects: Bioinformatics and Computational Biology

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.