Discriminating single-base difference miRNA expressions using microarray Probe Design Guru (ProDeG)

Inhan Lee, Subramanian S. Ajay, Haiming Chen, Atsushi Maruyama, Nulang Wang, Melvin G. Mcinnis, Brian D. Athey

Research output: Contribution to journalArticlepeer-review

Abstract

MicroRNAs (miRNA) are endogenous tissue-specific short RNAs that regulate gene expression. Discriminating each let-7 family member expression is especially important due to let-7's abundance and connection with development and cancer. However, short lengths (22 nt) and similarities between multiple sequences have prevented identification of individual members. Here, we present ProDeG, a computational algorithm which designs imperfectly matched sequences (previously yielding only noise levels in microarray experiments) for genome-wide microarray "signal" probes to discriminate single nucleotide differences and to improve probe qualities. Our probes for the entire let-7 family are both homogeneous and specific, verified using microarray signals from fluorescent dye-tagged oligonucleotides corresponding to the let-7 family, demonstrating the power of our algorithm. In addition, false let-7c signals from conventional perfectly-matched probes were identified in lymphoblastoid cell-line samples through comparison with our probe-set signals, raising concerns about false let-7 family signals in conventional microarray platform.

Original languageEnglish (US)
Article numbere27
JournalNucleic acids research
Volume36
Issue number5
DOIs
StatePublished - Mar 2008
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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