Skip Navigation



Nucleic Acids Research Advance Access published online on September 10, 2008
Nucleic Acids Research, doi:10.1093/nar/gkn556
This Article
Right arrow Full Text Freely available
Right arrow Print PDF (3436K) Freely available
Right arrow Screen PDF (1447K) Freely available
Right arrow Supplementary Data
Right arrowOA All Versions of this Article:
36/19/e126    most recent
gkn556v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Diskin, S. J.
Right arrow Articles by Wang, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Diskin, S. J.
Right arrow Articles by Wang, K.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2008 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.

Methods Online

Adjustment of genomic waves in signal intensities from whole-genome SNP genotyping platforms

Sharon J. Diskin1,2,3, Mingyao Li4, Cuiping Hou1, Shuzhang Yang5, Joseph Glessner6, Hakon Hakonarson6, Maja Bucan5, John M. Maris1,3,* and Kai Wang5,6

1Center for Childhood Cancer Research, Children's Hospital of Philadelphia, 2Genomics and Computational Biology, University of Pennsylvania, 3Department of Pediatrics, University of Pennsylvania, 4Department of Biostatistics and Epidemiology, University of Pennsylvania, 5Department of Genetics, University of Pennsylvania and 6Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA

*To whom correspondence should be addressed. Tel: +1 215 590 5244. Email: maris{at}chop.edu

Correspondence may also be addressed to Kai Wang. Tel: +1 267 426 2378; Email: wangk{at}chop.edu

Received April 19, 2008. Revised August 13, 2008. Accepted August 18, 2008.

Whole-genome microarrays with large-insert clones designed to determine DNA copy number often show variation in hybridization intensity that is related to the genomic position of the clones. We found these ‘genomic waves’ to be present in Illumina and Affymetrix SNP genotyping arrays, confirming that they are not platform-specific. The causes of genomic waves are not well-understood, and they may prevent accurate inference of copy number variations (CNVs). By measuring DNA concentration for 1444 samples and by genotyping the same sample multiple times with varying DNA quantity, we demonstrated that DNA quantity correlates with the magnitude of waves. We further showed that wavy signal patterns correlate best with GC content, among multiple genomic features considered. To measure the magnitude of waves, we proposed a GC-wave factor (GCWF) measure, which is a reliable predictor of DNA quantity (correlation coefficient = 0.994 based on samples with serial dilution). Finally, we developed a computational approach by fitting regression models with GC content included as a predictor variable, and we show that this approach improves the accuracy of CNV detection. With the wide application of whole-genome SNP genotyping techniques, our wave adjustment method will be important for taking full advantage of genotyped samples for CNV analysis.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Nucleic Acids ResHome page
L. Wan, K. Sun, Q. Ding, Y. Cui, M. Li, Y. Wen, R. C. Elston, M. Qian, and W. J Fu
Hybridization modeling of oligonucleotide SNP arrays for accurate DNA copy number estimation
Nucleic Acids Res., September 1, 2009; 37(17): e117 - e117.
[Abstract] [Full Text] [PDF]

Home page
 BioinformaticsHome page
L. Y. Wu, H. A. Chipman, S. B. Bull, L. Briollais, and K. Wang
A Bayesian segmentation approach to ascertain copy number variations at the population level
Bioinformatics, July 1, 2009; 25(13): 1669 - 1679.
[Abstract] [Full Text] [PDF]

Home page
 BioinformaticsHome page
R. Pique-Regi, A. Ortega, and S. Asgharzadeh
Joint estimation of copy number variation and reference intensities on multiple DNA arrays using GADA
Bioinformatics, May 15, 2009; 25(10): 1223 - 1230.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.