Cupid: simultaneous reconstruction of microRNA-target and ceRNA networks
- Hua-Sheng Chiu1,
- David Llobet-Navas2,
- Xuerui Yang3,
- Wei-Jen Chung4,
- Alberto Ambesi-Impiombato4,
- Archana Iyer4,
- Hyunjae Ryan Kim5,
- Elena G Seviour6,
- Zijun Luo6,
- Vasudha Sehgal6,
- Tyler Moss6,
- Yiling Lu6,
- Prahlad T Ram6,
- Jose M Silva2,
- Gordon B. Mills6,
- Andrea Califano4 and
- Pavel Sumazin1,7
- 1 Baylor College of Medicine;
- 2 Mount Sinai;
- 3 Tsinghua University;
- 4 Columbia University;
- 5 Rockefeller University;
- 6 MD Anderson Cancer Center
- ↵* Corresponding author; email: sumazin{at}bcm.edu
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.
- Received May 9, 2014.
- Accepted November 4, 2014.
- Published by Cold Spring Harbor Laboratory Press
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