Improvements to previous algorithms to predict gene structure and isoform concentrations using Affymetrix Exon arrays

BMC Bioinformatics. 2010 Nov 26:11:578. doi: 10.1186/1471-2105-11-578.

Abstract

Background: Exon arrays provide a way to measure the expression of different isoforms of genes in an organism. Most of the procedures to deal with these arrays are focused on gene expression or on exon expression. Although the only biological analytes that can be properly assigned a concentration are transcripts, there are very few algorithms that focus on them. The reason is that previously developed summarization methods do not work well if applied to transcripts. In addition, gene structure prediction, i.e., the correspondence between probes and novel isoforms, is a field which is still unexplored.

Results: We have modified and adapted a previous algorithm to take advantage of the special characteristics of the Affymetrix exon arrays. The structure and concentration of transcripts -some of them possibly unknown- in microarray experiments were predicted using this algorithm. Simulations showed that the suggested modifications improved both specificity (SP) and sensitivity (ST) of the predictions. The algorithm was also applied to different real datasets showing its effectiveness and the concordance with PCR validated results.

Conclusions: The proposed algorithm shows a substantial improvement in the performance over the previous version. This improvement is mainly due to the exploitation of the redundancy of the Affymetrix exon arrays. An R-Package of SPACE with the updated algorithms have been developed and is freely available.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Alternative Splicing
  • Databases, Genetic
  • Exons*
  • Gene Expression Profiling / methods*
  • Oligonucleotide Array Sequence Analysis / methods*
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Sensitivity and Specificity

Substances

  • Protein Isoforms