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Bioinformatics Advance Access published online on February 4, 2009
Bioinformatics, doi:10.1093/bioinformatics/btp074
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©2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

A single-sample method for normalizing and combining full-resolution copy numbers from multiple platforms, labs and analysis methods

Henrik Bengtsson a,*, Amrita Ray b, Paul Spellman b and Terence P. Speed a,c

a Department of Statistics, University of California, Berkeley, USA. b Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, USA. c Bioinformatics Division, Walter & Eliza Hall Institute of Medical Research, Parkville, Australia.

*To whom correspondence should be addressed. Henrik Bengtsson, E-mail: hb{at}stat.berkeley.edu, henrik.bengtsson{at}gmail.com


  Abstract

Motivation: The rapid expansion ofwhole-genome copy-number (CN) studies brings a demand for increased precision and resolution of CN estimates. Recent studies have obtained CNestimates frommore than one platformon the same samples, and it is natural to want to combine the different estimates in order to meet this demand. Estimates from different platforms show different degrees of attenuation of the true CN changes. Similar differences can be observed in CNs from the same platformrun in different labs, or in the same lab, with different analytical methods. This is the reason why it is not straightforward to combine CN estimates from different sources (platforms, labs, analysis methods).

Results: We propose a single-sample multi-source normalization that brings full-resolution CN estimates to the same scale across sources. The normalized CNs are such that for any underlying CN level, their mean level is the same regardless of source, which make them better suited for being combined across sources, e.g. existing segmentation methodsmay be used to identify aberrant regions.We use microarraybased CN estimates from The Cancer Genome Atlas (TCGA) project to illustrate and validate the method. We show that the normalized and combined data better separate two CN states at a given resolution. We conclude that it is possible to combine CNs from multiple sources such that the resolution becomes effectively larger, and when multiple platforms are combined, they also enhance the genome coverage by complementing each other in different regions.

Availability: A bounded-memory implementation is available in aroma.cn.

Contact: hb{at}stat.berkeley.edu

Associate Editor: Prof. John Quackenbush

Received on November 19, 2008; revised on January 9, 2009; accepted on January 30, 2009

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H. Bengtsson, P. Wirapati, and T. P. Speed
A single-array preprocessing method for estimating full-resolution raw copy numbers from all Affymetrix genotyping arrays including GenomeWideSNP 5 & 6
Bioinformatics, September 1, 2009; 25(17): 2149 - 2156.
[Abstract] [Full Text] [PDF]


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