An imputation approach for oligonucleotide microarrays

PLoS One. 2013;8(3):e58677. doi: 10.1371/journal.pone.0058677. Epub 2013 Mar 7.

Abstract

Oligonucleotide microarrays are commonly adopted for detecting and qualifying the abundance of molecules in biological samples. Analysis of microarray data starts with recording and interpreting hybridization signals from CEL images. However, many CEL images may be blemished by noises from various sources, observed as "bright spots", "dark clouds", and "shadowy circles", etc. It is crucial that these image defects are correctly identified and properly processed. Existing approaches mainly focus on detecting defect areas and removing affected intensities. In this article, we propose to use a mixed effect model for imputing the affected intensities. The proposed imputation procedure is a single-array-based approach which does not require any biological replicate or between-array normalization. We further examine its performance by using Affymetrix high-density SNP arrays. The results show that this imputation procedure significantly reduces genotyping error rates. We also discuss the necessary adjustments for its potential extension to other oligonucleotide microarrays, such as gene expression profiling. The R source code for the implementation of approach is freely available upon request.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Gene Dosage
  • Genotyping Techniques / methods
  • Genotyping Techniques / standards
  • Oligonucleotide Array Sequence Analysis / methods*
  • Oligonucleotide Array Sequence Analysis / standards*
  • Polymorphism, Single Nucleotide
  • Reproducibility of Results

Grants and funding

This work was partly supported by the Summer Oncology Scholarship from Michigan State University and the startup funds from University of Arkansas for Medical Sciences. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.