Cupid: simultaneous reconstruction of microRNA-target and ceRNA networks
- Hua-Sheng Chiu1,2,3,4,12,
- David Llobet-Navas5,12,
- Xuerui Yang6,
- Wei-Jen Chung1,2,3,
- Alberto Ambesi-Impiombato7,8,
- Archana Iyer1,
- Hyunjae Ryan Kim9,
- Elena G. Seviour10,
- Zijun Luo10,
- Vasudha Sehgal10,
- Tyler Moss10,
- Yiling Lu10,
- Prahlad Ram10,
- José Silva5,
- Gordon B. Mills10,
- Andrea Califano1,2,3,7,8,11 and
- Pavel Sumazin4
- 1Department of Systems Biology,
- 2Center for Computational Biology and Bioinformatics,
- 3Department of Biomedical Informatics, Columbia University, New York, New York 10032, USA;
- 4Texas Children’s Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA;
- 5Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA;
- 6MOE Key Laboratory of Bioinformatics, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China;
- 7Institute for Cancer Genetics,
- 8Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York 10032, USA;
- 9Laboratory of RNA Molecular Biology, Rockefeller University, New York, New York 10065, USA;
- 10Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA;
- 11Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA
- Corresponding authors: califano{at}c2b2.columbia.edu, sumazin{at}bcm.edu
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↵12 These authors contributed equally to this work.
Abstract
We introduce a method for simultaneous prediction of microRNA–target interactions and their mediated competitive endogenous RNA (ceRNA) interactions. Using high-throughput validation assays in breast cancer cell lines, we show that our integrative approach significantly improves on microRNA–target prediction accuracy as assessed by both mRNA and protein level measurements. Our biochemical assays support nearly 500 microRNA–target interactions with evidence for regulation in breast cancer tumors. Moreover, these assays constitute the most extensive validation platform for computationally inferred networks of microRNA–target interactions in breast cancer tumors, providing a useful benchmark to ascertain future improvements.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.178194.114.
- Received May 9, 2014.
- Accepted November 4, 2014.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
