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Using expression profiling data to identify human microRNA targets

Nature Methods volume 4, pages 1045–1049 (2007)Cite this article

Abstract

We demonstrate that paired expression profiles of microRNAs (miRNAs) and mRNAs can be used to identify functional miRNA-target relationships with high precision. We used a Bayesian data analysis algorithm, GenMiR++, to identify a network of 1,597 high-confidence target predictions for 104 human miRNAs, which was supported by RNA expression data across 88 tissues and cell types, sequence complementarity and comparative genomics data. We experimentally verified our predictions by investigating the result of let-7b downregulation in retinoblastoma using quantitative reverse transcriptase (RT)-PCR and microarray profiling: some of our verified let-7b targets include CDC25A and BCL7A. Compared to sequence-based predictions, our high-scoring GenMiR++ predictions had much more consistent Gene Ontology annotations and were more accurate predictors of which mRNA levels respond to changes in let-7b levels.

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Figure 1: The GenMiR++ network of let-7b targets.
Figure 2: Reduced levels of let-7b parallel increased levels of GenMiR++ targets in retinoblastoma.
Figure 3: Increasing levels of let-7b reveals enrichment of GenMiR++ targets among downregulated genes.

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Acknowledgements

J.C.H. and T.B. were supported by Natural Science and Engineering Research Council postgraduate scholarships. T.W.C. was supported by a Canada Graduate Scholarship from the Canadian Institutes for Health Research (CIHR). This study was supported by a Natural Sciences and Engineering Research Council operating grant and Canadian Foundation for Innovation and Ontario Research Fund infrastructure grants to Q.D.M.; a CIHR grant to B.J.F. and T.R.H; an Ontario Genomics Institute and Genome Canada grant to B.J.F. and B.J.B.; a CIHR and National Cancer Institute of Canada grant to B.J.B.; and a US National Institutes of Health grant to B.L.G. B.J.F. is a Fellow of the Canadian Institute for Advanced Research.

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Author notes

  1. Timothy W Corson

    Present address: Present address: Department of Molecular, Cellular and Developmental Biology, Yale University, P.O. Box 208103, New Haven, Connecticut 06520, USA.,

  2. Jim C Huang and Tomas Babak: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Electrical and Computer Engineering, University of Toronto, 10 King's College Road, Toronto, M5S 3G4, Ontario, Canada

    Jim C Huang & Brendan J Frey

  2. Department of Molecular and Medical Genetics, University of Toronto, 1 King's College Rd., Toronto, M5S 1A8, Ontario, Canada

    Tomas Babak, Timothy W Corson, Brenda L Gallie, Timothy R Hughes, Benjamin J Blencowe & Quaid D Morris

  3. Division of Applied Molecular Oncology, Ontario Cancer Institute/Princess Margaret Hospital, University Health Network, Toronto, M5G 2M9, Ontario, Canada

    Timothy W Corson, Sofia Khan & Brenda L Gallie

  4. Banting and Best Department of Medical Research, University of Toronto, 160 College Street, Toronto, M5G 1L6, Ontario, Canada

    Gordon Chua, Timothy R Hughes, Benjamin J Blencowe, Brendan J Frey & Quaid D Morris

  5. Department of Computer Science, University of Toronto, 10 King's College Road, Toronto, M5S 3G4, Ontario, Canada

    Brendan J Frey & Quaid D Morris

Authors
  1. Jim C Huang
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  2. Tomas Babak
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Corresponding authors

Correspondence to Brendan J Frey or Quaid D Morris.

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Supplementary Figures 1–6, Supplementary Tables 1–2, Supplementary Methods (PDF 2123 kb)

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Huang, J., Babak, T., Corson, T. et al. Using expression profiling data to identify human microRNA targets. Nat Methods 4, 1045–1049 (2007). https://doi.org/10.1038/nmeth1130

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