title: miSTAR: miRNA target prediction through modeling quantitative and qualitative miRNA binding site information in a stacked model structure.
abstract: In microRNA (miRNA) target prediction, typically two levels of information need to be modeled: the number of potential miRNA binding sites present in a target mRNA and the genomic context of each individual site. Single model structures insufficiently cope with this complex training data structure, consisting of feature vectors of unequal length as a consequence of the varying number of miRNA binding sites in different mRNAs. To circumvent this problem, we developed a two-layered, stacked model, in which the influence of binding site context is separately modeled. Using logistic regression and random forests, we applied the stacked model approach to a unique data set of 7990 probed miRNA-mRNA interactions, hereby including the largest number of miRNAs in model training to date. Compared to lower-complexity models, a particular stacked model, named miSTAR (miRNA stacked model target prediction; www.mi-star.org), displays a higher general performance and precision on top scoring predictions. More importantly, our model outperforms published and widely used miRNA target prediction algorithms. Finally, we highlight flaws in cross-validation schemes for evaluation of miRNA target prediction models and adopt a more fair and stringent approach.
authors.affiliation: Center for Medical Genetics Ghent (CMGG), Ghent University, B-9000 Ghent, Belgium.
authors.forename: Gert
authors.initials: G
authors.lastname: Van Peer
authors.affiliation: Research Unit Knowledge-based Systems (KERMIT), Department of Mathematical Modeling, Statistics and Bioinformatics, Ghent University, B-9000 Ghent, Belgium.
authors.forename: Ayla
authors.initials: A
authors.lastname: De Paepe
authors.affiliation: Research Unit Knowledge-based Systems (KERMIT), Department of Mathematical Modeling, Statistics and Bioinformatics, Ghent University, B-9000 Ghent, Belgium.|Bioinformatics Institute Ghent N2N (BIG N2N), Ghent University, B-9000 Ghent, Belgium.
authors.forename: Michiel
authors.initials: M
authors.lastname: Stock
authors.affiliation: Center for Medical Genetics Ghent (CMGG), Ghent University, B-9000 Ghent, Belgium.|Bioinformatics Institute Ghent N2N (BIG N2N), Ghent University, B-9000 Ghent, Belgium.|Cancer Research Institute Ghent (CRIG), Ghent University, B-9000 Ghent, Belgium.
authors.forename: Jasper
authors.initials: J
authors.lastname: Anckaert
authors.affiliation: Center for Medical Genetics Ghent (CMGG), Ghent University, B-9000 Ghent, Belgium.|Bioinformatics Institute Ghent N2N (BIG N2N), Ghent University, B-9000 Ghent, Belgium.|Cancer Research Institute Ghent (CRIG), Ghent University, B-9000 Ghent, Belgium.
authors.forename: Pieter-Jan
authors.initials: PJ
authors.lastname: Volders
authors.affiliation: Center for Medical Genetics Ghent (CMGG), Ghent University, B-9000 Ghent, Belgium.|Bioinformatics Institute Ghent N2N (BIG N2N), Ghent University, B-9000 Ghent, Belgium.|Cancer Research Institute Ghent (CRIG), Ghent University, B-9000 Ghent, Belgium.
authors.forename: Jo
authors.initials: J
authors.lastname: Vandesompele
authors.affiliation: Research Unit Knowledge-based Systems (KERMIT), Department of Mathematical Modeling, Statistics and Bioinformatics, Ghent University, B-9000 Ghent, Belgium.|Bioinformatics Institute Ghent N2N (BIG N2N), Ghent University, B-9000 Ghent, Belgium.
authors.forename: Bernard
authors.initials: B
authors.lastname: De Baets
authors.affiliation: Research Unit Knowledge-based Systems (KERMIT), Department of Mathematical Modeling, Statistics and Bioinformatics, Ghent University, B-9000 Ghent, Belgium.|Bioinformatics Institute Ghent N2N (BIG N2N), Ghent University, B-9000 Ghent, Belgium.
authors.forename: Willem
authors.initials: W
authors.lastname: Waegeman
mesh_terms: D020413:3' Untranslated Regions; D000465:Algorithms; D001665:Binding Sites; D006801:Humans; D000069550:Machine Learning; D035683:MicroRNAs / Q000378:metabolism*; D008957:Models, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D012984:Software
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D012333:RNA, Messenger