Cupid: simultaneous reconstruction of microRNA-target and ceRNA networks.
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.
Department of Systems Biology, Center for Computational Biology and Bioinformatics, Department of Biomedical Informatics, Columbia University, New York, New York 10032, USA; Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA;
Hua-Sheng
HS
Chiu
Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA;
David
D
Llobet-Navas
MOE Key Laboratory of Bioinformatics, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China;
Xuerui
X
Yang
Department of Systems Biology, Center for Computational Biology and Bioinformatics, Department of Biomedical Informatics, Columbia University, New York, New York 10032, USA;
Wei-Jen
WJ
Chung
Institute for Cancer Genetics, Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York 10032, USA;
Alberto
A
Ambesi-Impiombato
Department of Systems Biology.
Archana
A
Iyer
Laboratory of RNA Molecular Biology, Rockefeller University, New York, New York 10065, USA;
Hyunjae Ryan
HR
Kim
Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA;
Elena G
EG
Seviour
Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA;
Zijun
Z
Luo
Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA;
Vasudha
V
Sehgal
Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA;
Tyler
T
Moss
Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA; califano@c2b2.columbia.edu sumazin@bcm.edu.
Yiling
Y
Lu
Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA;
Prahlad
P
Ram
Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA;
José
J
Silva
Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA;
Gordon B
GB
Mills
Department of Systems Biology, Center for Computational Biology and Bioinformatics, Department of Biomedical Informatics, Columbia University, New York, New York 10032, USA; Institute for Cancer Genetics, Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York 10032, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA califano@c2b2.columbia.edu sumazin@bcm.edu.
Andrea
A
Califano
Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA;
Pavel
P
Sumazin
D020413:3' Untranslated Regions; D000465:Algorithms; D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods*; D004843:Epistasis, Genetic; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D034622:RNA Interference; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics*
D020413:3' Untranslated Regions; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D035683:MicroRNAs; D012333:RNA, Messenger