miTAR: a hybrid deep learning-based approach for predicting miRNA targets.

Tongjun Gu, Xiwu Zhao, William Bradley Barbazuk, Ji-Hyun Lee
Author Information
  1. Tongjun Gu: Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, FL, USA. tgu@ufl.edu. ORCID
  2. Xiwu Zhao: Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, USA.
  3. William Bradley Barbazuk: Bioinformatics, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, FL, USA.
  4. Ji-Hyun Lee: Division of Quantitative Sciences, University of Florida Health Cancer Center, University of Florida, Gainesville, FL, USA.

Abstract

BACKGROUND: microRNAs (miRNAs) have been shown to play essential roles in a wide range of biological processes. Many computational methods have been developed to identify targets of miRNAs. However, the majority of these methods depend on pre-defined features that require considerable efforts and resources to compute and often prove suboptimal at predicting miRNA targets.
RESULTS: We developed a novel hybrid deep learning-based (DL-based) approach that is capable of predicting miRNA targets at a higher accuracy. This approach integrates convolutional neural networks (CNNs) that excel in learning spatial features and recurrent neural networks (RNNs) that discern sequential features. Therefore, our approach has the advantages of learning both the intrinsic spatial and sequential features of miRNA:target. The inputs for our approach are raw sequences of miRNAs and genes that can be obtained effortlessly. We applied our approach on two human datasets from recently miRNA target prediction studies and trained two models. We demonstrated that the two models consistently outperform the previous methods according to evaluation metrics on test datasets. Comparing our approach with currently available alternatives on independent datasets shows that our approach delivers substantial improvements in performance. We also show with multiple evidences that our approach is more robust than other methods on small datasets. Our study is the first study to perform comparisons across multiple existing DL-based approaches on miRNA target prediction. Furthermore, we examined the contribution of a Max pooling layer in between the CNN and RNN and demonstrated that it improves the performance of all our models. Finally, a unified model was developed that is robust on fitting different input datasets.
CONCLUSIONS: We present a new DL-based approach for predicting miRNA targets and demonstrate that our approach outperforms the current alternatives. We supplied an easy-to-use tool, miTAR, at https://github.com/tjgu/miTAR . Furthermore, our analysis results support that Max Pooling generally benefits the hybrid models and potentially prevents overfitting for hybrid models.

Keywords

References

  1. Nat Genet. 2019 Jan;51(1):12-18 [PMID: 30478442]
  2. IEEE/ACM Trans Comput Biol Bioinform. 2016 Nov;13(6):1161-1169 [PMID: 28055894]
  3. Pac Symp Biocomput. 2016;22:254-265 [PMID: 27896980]
  4. J Physiol Biochem. 2011 Mar;67(1):129-39 [PMID: 20981514]
  5. Bioinformatics. 2019 Jul 15;35(14):i269-i277 [PMID: 31510640]
  6. Nat Genet. 2007 Oct;39(10):1278-84 [PMID: 17893677]
  7. Bioinformatics. 2018 Nov 15;34(22):3781-3787 [PMID: 29868708]
  8. Front Genet. 2014 Feb 18;5:23 [PMID: 24600468]
  9. Cell. 2010 Apr 2;141(1):129-41 [PMID: 20371350]
  10. Brief Funct Genomics. 2019 Feb 14;18(1):41-57 [PMID: 30265280]
  11. Nucleic Acids Res. 2016 Jan 4;44(D1):D239-47 [PMID: 26590260]
  12. Genome Biol. 2014;15(10):500 [PMID: 25344330]
  13. Cell. 2013 Apr 25;153(3):654-65 [PMID: 23622248]
  14. Nucleic Acids Res. 2016 Jun 20;44(11):e107 [PMID: 27084946]
  15. Nucleic Acids Res. 2018 Sep 19;46(16):8105-8113 [PMID: 29986088]
  16. Cell. 2018 Mar 22;173(1):20-51 [PMID: 29570994]
  17. Cell. 2005 Jan 14;120(1):15-20 [PMID: 15652477]
  18. Mol Cell. 2014 Jun 19;54(6):1042-1054 [PMID: 24857550]
  19. PLoS Comput Biol. 2018 Jul 13;14(7):e1006185 [PMID: 30005074]
  20. Genome Biol. 2003;5(1):R1 [PMID: 14709173]
  21. Nucleic Acids Res. 2015 Jan;43(Database issue):D153-9 [PMID: 25416803]
  22. Nat Rev Genet. 2015 Jul;16(7):421-33 [PMID: 26077373]
  23. Elife. 2015 Aug 12;4: [PMID: 26267216]

MeSH Term

Deep Learning
Humans
MicroRNAs
Neural Networks, Computer

Chemicals

MicroRNAs

Word Cloud

Created with Highcharts 10.0.0approachmiRNAtargetsdatasetsmodelsmethodsfeaturespredictinghybridneuralnetworksmiRNAsdevelopedDL-basedlearningtwotargetdeeplearning-basedspatialsequentialpredictiondemonstratedalternativesperformancemultiplerobuststudyFurthermoreMaxmodelBACKGROUND:microRNAsshownplayessentialroleswiderangebiologicalprocessesManycomputationalidentifyHowevermajoritydependpre-definedrequireconsiderableeffortsresourcescomputeoftenprovesuboptimalRESULTS:novelcapablehigheraccuracyintegratesconvolutionalCNNsexcelrecurrentRNNsdiscernThereforeadvantagesintrinsicmiRNA:targetinputsrawsequencesgenescanobtainedeffortlesslyappliedhumanrecentlystudiestrainedconsistentlyoutperformpreviousaccordingevaluationmetricstestComparingcurrentlyavailableindependentshowsdeliverssubstantialimprovementsalsoshowevidencessmallfirstperformcomparisonsacrossexistingapproachesexaminedcontributionpoolinglayerCNNRNNimprovesFinallyunifiedfittingdifferentinputCONCLUSIONS:presentnewdemonstrateoutperformscurrentsuppliedeasy-to-usetoolmiTARhttps://githubcom/tjgu/miTARanalysisresultssupportPoolinggenerallybenefitspotentiallypreventsoverfittingmiTAR:ConvolutionalDeepHybridMiRNARecurrent

Similar Articles

Cited By