Identifiability of isoform deconvolution from junction arrays and RNA-Seq

Bioinformatics. 2009 Dec 1;25(23):3056-9. doi: 10.1093/bioinformatics/btp544. Epub 2009 Sep 16.

Abstract

Motivation: Splice junction microarrays and RNA-seq are two popular ways of quantifying splice variants within a cell. Unfortunately, isoform expressions cannot always be determined from the expressions of individual exons and splice junctions. While this issue has been noted before, the extent of the problem on various platforms has not yet been explored, nor have potential remedies been presented.

Results: We propose criteria that will guarantee identifiability of an isoform deconvolution model on exon and splice junction arrays and in RNA-Seq. We show that up to 97% of 2256 alternatively spliced human genes selected from the RefSeq database lead to identifiable gene models in RNA-seq, with similar results in mouse. However, in the Human Exon array only 26% of these genes lead to identifiable models, and even in the most comprehensive splice junction array only 69% lead to identifiable models.

Supplementary information: Supplementary data are available at Bioinformatics online.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing*
  • Animals
  • Base Sequence
  • Computational Biology / methods
  • Gene Expression Profiling
  • Humans
  • Mice
  • Oligonucleotide Array Sequence Analysis / methods*
  • Protein Isoforms / genetics*
  • Protein Isoforms / metabolism
  • RNA / chemistry*
  • RNA / metabolism

Substances

  • Protein Isoforms
  • RNA