Skip Navigation



Bioinformatics Advance Access published online on October 23, 2006
Bioinformatics, doi:10.1093/bioinformatics/btl542
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow Supplementary Data
Right arrowOA All Versions of this Article:
22/24/3054    most recent
btl542v1
Right arrow Comments: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when Comments are posted
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
Google Scholar
Right arrow Articles by Yuan, D. S.
Right arrow Articles by Irizarry, R. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yuan, D. S.
Right arrow Articles by Irizarry, R. A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2006 The Author(s)
Received April 28, 2006
Revised August 3, 2006
Accepted October 12, 2006

Article

High-resolution spatial normalization for microarrays containing embedded technical replicates

Daniel S. Yuan 1 * and Rafael A. Irizarry 2

1 Department of Molecular Biology and Genetics, School of Medicine, Johns Hopkins University, Baltimore MD, 21205, USA; High-throughput Biology Center, School of Medicine, Johns Hopkins University, Baltimore MD, 21205, USA; Department of Biostatistics, Bloomberg School of Public Health. Johns Hopkins University, Baltimore MD, 21205, USA
2 Department of Biostatistics, Bloomberg School of Public Health. Johns Hopkins University, Baltimore MD, 21205, USA


  Abstract

Motivation: Microarray data are susceptible to a wide range of artifacts, many of which occur on physical scales comparable to the spatial dimensions of the array. These artifacts introduce biases that are spatially correlated. The ability of current methodologies to detect and correct such biases is limited.

Results: We introduce a new approach for analyzing spatial artifacts, termed "conditional residual analysis for microarrays" (CRAM). CRAM requires a microarray design that contains technical replicates of representative features and a limited number of negative controls, but is free of the assumptions that constrain existing analytical procedures. The key idea is to extract residuals from sets of matched replicates to generate residual images. The residual images reveal spatial artifacts with single-feature resolution. Surprisingly, spatial artifacts were found to coexist independently as additive and multiplicative errors. Efficient procedures for bias estimation were devised to correct the spatial artifacts on both intensity scales. In a survey of 484 published single-channel datasets, variance fell 4- to 12-fold in 5% of the datasets after bias correction. Thus, inclusion of technical replicates in a microarray design affords benefits far beyond what one might expect with a conventional ‘n=5’ averaging, and should be considered when designing any microarray for which randomization is feasible.

Availability: CRAM is implemented as version 2 of the hoptag software package for R, which is included in the Supplementary Information.

Associate Editor: Alvis Brazma
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
 BioinformaticsHome page
J. R. Bayjanov, M. Wels, M. Starrenburg, J. E. T. van Hylckama Vlieg, R. J. Siezen, and D. Molenaar
PanCGH: a genotype-calling algorithm for pangenome CGH data
Bioinformatics, February 1, 2009; 25(3): 309 - 314.
[Abstract] [Full Text] [PDF]

Home page
 BioinformaticsHome page
J. M. Cairns, M. J. Dunning, M. E. Ritchie, R. Russell, and A. G. Lynch
BASH: a tool for managing BeadArray spatial artefacts
Bioinformatics, December 15, 2008; 24(24): 2921 - 2922.
[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.