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DeepRibSt: a multi-feature convolutional neural network for predicting ribosome stalling

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Abstract

Ribosomes are a kind of organelle in cells, which are mainly involved in the translation process of genetic materials, but the underlying mechanisms associated with ribosome stalling are not fully understood. Thanks to the development of biological experimental techniques, many ribosome footprintings are generated, which can help us to study ribosome stalling. Effectively obtaining a precise ribosome stalling site will be helpful for the treatment of the related diseases, however there is still much room for the improvement of ribosome stalling prediction. In this study, we propose a new deep neural network model named DeepRibSt for the prediction of ribosome stalling sites. We first process the ribosome footprinting data to the training set. Then three new features, including evolutionary conservation, hydrophobicity, and amino dissociation constant, along with the previous sequence features, are extracted as input to the network. To improve the performance of the algorithm in ribosome stalling prediction, we use two convolutional layers and three fully connected layers to design a new network architecture. To verify the validity of our proposed DeepRibSt, we compare DeepRibSt with four popular deep neural networks, i.e., AlexNet, LeNet, ResNet, and LSTM on human (i.e., Battle2015 and Stumpf13) and yeast (i.e., Pop2014, Young15, and Brar12) data. To further demonstrate the effectiveness of DeepRibS, we compare DeepRibSt with the state-of-the-art method. The experimental results show that DeepRibSt outperforms all other methods and achieves the state-of-the-art performance in accuracy, recall, specificity, F1-score, and the area under the receiver operating characteristic curve (AUC).

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References

  1. Alipanahi B, Delong A, Weirauch MT, Frey BJ (2015) Predicting the sequence specificities of DNA and RNA-binding proteins by deep learning. Nat Biotech 33(8):831–838

    Article  Google Scholar 

  2. Ashish S, jain Ritesh (2012) Scikit-learn: Machine Learning in Python. J Mach Learn Res 12(10):2825–2830

    MathSciNet  Google Scholar 

  3. Ashkenazy H, Erez E, Martz E, Pupko T, Tal NB (2010) Consurf 2010: calculating evolutionary conservation in sequence and structure of proteins and nucleic acids Nucleic Acids Res W529–W533

  4. Battle A, Khan Z, Wang SH, Mitrano A, Ford MJ, Pritchard JK, Gilad Y (2015) Impact of regulatory variation from RNA to protein. Science 347(6222):664–667

    Article  Google Scholar 

  5. Bazzini AA, Lee MT, Giraldez AJ (2012) Ribosome Profiling Shows That miR-430 Reduces Translation Before Causing mRNA Decay in Zebrafish. Science 336(6078):233–237

    Article  Google Scholar 

  6. Bischoff L, Berninghausen O, Beckmann R (2014) Molecular basis for the ribosome functioning as an L-Tryptophan sensor. Cell Reports 9(2):469–475

    Article  Google Scholar 

  7. Bjornsti MA, Houghton PJ (2004) Lost in translation: Dysregulation of cap-dependent translation and cancer. Cancer Cell 5(6):519–523

    Article  Google Scholar 

  8. Borreca A, Gironi K, Amadoro G, Ammassari-Teule M (2016) Opposite dysregulation of Fragile-X mental retardation protein and heteronuclear ribonucleoprotein c protein associates with enhanced APP translation in alzheimer disease. Molecular Neurobiology 53(5):3227–3234

    Article  Google Scholar 

  9. Bottou L, Bengio Y, Cun YL (1997) Global training of document processing systems using graph transformer networks IEEE conference on computer vision and pattern recognition 489–494

  10. Brar GA, Weissman JS (2015) Ribosome profiling reveals the what, when, where and how of proteinsynthesis. Nat Rev Mol Cell Biol 16(11):651–664

    Article  Google Scholar 

  11. Brar GA, Yassour M, Friedman N, Regev A, Ingolia NT, Weissman JS (2012) High-Resolution View of the yeast meiotic program revealed by ribosome profiling. Science 335(6068):552–557

    Article  Google Scholar 

  12. Brodie BB, Kurz H, Schanker LS (1960) The importance of dissociation constant and lipid-solubility in influencing the passage of drugs into the cerebrospinal fluid. J Pharmacol Exp Ther 130(130):20–25

    Google Scholar 

  13. Chakraborty R, Hasija Y (2019) Predicting microRNA sequence using CNN and LSTM stacked in Seq2Seq architecture. IEEE/ACM Transactions on Computational Biology and Bioinformatics, https://doi.org/10.1109/TCBB.2019.2936186. [Epub ahead of print]

  14. Chaney JL, Clark PL (2015) Roles for synonymous codon usage in protein biogenesis. Annu Rev Biophys 44:143–166

    Article  Google Scholar 

  15. Collobert R, Weston J (2008) A unified architecture for natural language processing: deep neural networks with multitask learning. In: proceedings of the 25th international conference on machine learning, pp 160–167

  16. Fang SH, Tsao Y, Hsiao MJ, Chen JY, Lai YH, Lin FC, Wang CT (2019) Detection of pathological voice using cepstrum vectors: a deep learning approach. J Voice 33(5):634–641

    Article  Google Scholar 

  17. He K, Zhang X, Ren S, Sun J (2016) Deep Residual learning for Image Recognition, https://doi.org/10.1109/CVPR.2016.90 IEEE conference on computer vision pattern recognition 770–778

  18. Hu K, Shen BW, Zhang Y, Cao CH, Xiao F, Gao XP (2019) Automatic segmentation of retinal layer boundaries in OCT images using multiscale convolutional neural network and graph search. Neurocomputing 365:302–313

    Article  Google Scholar 

  19. Huang Z, Xu W, Yu K (2015) Bidirectional LSTM-CRF models for sequence tagging. arXiv:1508.01991

  20. Hubbard T (2002) The Ensembl genome database project. Nucleic Acids Res 30(1):38–41

    Article  MathSciNet  Google Scholar 

  21. Ingolia NT (2016) Ribosome footprint profiling of translation throughout the genome. Cell 165(1):22–33

    Article  Google Scholar 

  22. Ingolia NT, Ghaemmaghami S, Newman JRS, Weissman JS (2009) Genome-Wide Analysis in vivo of translation with nucleotide resolution using ribosome profiling. Science 324(5924):218–223

    Article  Google Scholar 

  23. Ingolia NT, Lareau LF, Weissman JS (2011) Ribosome profiling of mouse embryonic stem cells reveals the complexity and dynamics of mammalian proteomes. Cell 147(4):789–802

    Article  Google Scholar 

  24. Johnsson P, Lipovich L, Grandér D, Morris KV (2014) Evolutionary conservation of long non-coding RNAs; sequence, structure, function. Biochimica Et Biophysica Acta 1840(3):1063–71

    Article  Google Scholar 

  25. Krizhevsky A, Sutskever I, Hinton GE (2012) Imagenet classification with deep convolutional neural networks. In: International Conference on Neural Information Processing Systems Curran Associates Inc, pp 1097–1105

  26. Lecun Y, Bottou L, Bengio Y, Haffner P (1998) Gradient-based learning applied to document recognition. Proc IEEE 86(11):2278–2324

    Article  Google Scholar 

  27. Lucent D, Snow CD, Aitken CE, Pande VS (2010) Non-Bulk-Like Solvent behavior in the ribosome exit tunnel. PLOS 6(10):e1000963

    Google Scholar 

  28. Michel AM, Choudhury KR, Firth AE, Ingolia NT (2012) Observation of dually decoded regions of the human genome using ribosome profiling data. Genome Res 22(11):2219–2229

    Article  Google Scholar 

  29. Michel AM, Fox G, M Kiran A, De Bo C, O’Connor PB, Heaphy SM, Mullan JP, Donohue CA, Higgins DG, Baranov PV (2014) GWIPS-Viz: development of a ribo-seq genome browser. Nucleic Acids Res 42(Datebase issue):D859–64

    Article  Google Scholar 

  30. Molchanov P, Tyree S, Karras T, Aila T, Kautz J (2017) Pruning convolutional neural networks for resource efficient inference. arXiv:1611.06440v2

  31. Pan X, Shen H (2017) RNA-Protein binding motifs mining with a new hybrid deep learning based cross-domain knowledge integration approach. BMC Bioinforma 18:136

    Article  Google Scholar 

  32. Pla A, Zhong X, Rayner S (2018) miRAW: A deep learning-based approach to predict microRNA targets by analyzing whole microRNA transcripts. PLoS Comput Biol 14(7):e1006185

    Article  Google Scholar 

  33. Pollard KS, Hubisz MJ, Rosenbloom KR, Siepel A (2010) Detection of nonneutral substitution rates on mammalian phylogenies. Genome Res 20 (1):110–121

    Article  Google Scholar 

  34. Pop C, Rouskin S, Ingolia NT, Han L, Phizicky EM, Weissman JS, Koller D (2014) Causal signals between codon bias, m RNA structure, and the efficiency of translation and elongation. Mol Syst Biol 10(12):770

    Article  Google Scholar 

  35. Quan TE, Claassens NJ, Soll D, van der Oost J (2015) Codon bias as a means to Fine-Tune gene expression. Mol Cell 59(2):149–61

    Article  Google Scholar 

  36. Sauna ZE, Kimchi SC (2011) Understanding the contribution of synonymous mutations to human disease. Nat Rev Genet 12(10):683–691

    Article  Google Scholar 

  37. Siepel A, Bejerano G, Pedersen JS, Hinrichs AS, Hou M, Rosenbloom K, Clawson H, Spieth J, Hillier LW, Richards S, Weinstock GM, Wilson RK, Gibbs RA, Kent WJ, Miller W, Haussler D (2005) Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res 15 (8):1034–1050

    Article  Google Scholar 

  38. Stumpf C, Moreno M, Olshen A, Taylor B, Ruggero D (2013) The translational landscape of the mammalian cell cycle. Mol Cell 52(4):574–582

    Article  Google Scholar 

  39. Tanner DR, Cariello DA, Woolstenhulme CJ, Broadbent MA, Buskirk AR (2009) Genetic identification of nascent peptides that induce ribosome stalling. J Biol Chem 284(50):34809–34818

    Article  Google Scholar 

  40. Tsai CJ, Sauna ZE, Kimchi-Sarfaty C, Ambudkar SV, Gottesman MM, Nussinov R (2008) Synonymous mutations and ribosome stalling can lead to altered folding pathways and distinct minima. J Mol Biol 383(2):281–91

    Article  Google Scholar 

  41. Vázquez-Laslop N, Klepacki D, Mulhearn DC, Ramu H, Krasnykh O, Franzblau S, Mankin AS (2011) Role of antibiotic Iigand in nascent peptide-dependent ribosome stalling. Proceedings of the national academy of sciences of the United States of America 108(26):10496–501

    Article  Google Scholar 

  42. Vazquez-Laslop N, Thum C, Mankin AS (2018) Molecular mechanism of drug-dependent ribosome stalling. Mol Cell 30(2):190–202

    Article  Google Scholar 

  43. Wang ET, Taliaferro JM, Lee JA, Sudhakaran IP, Rossoll W, Gross C, Moss KR, Bassell GJ (2016) Dysregulation of mRNA Localization and Translation in Genetic Disease. JNEUROSCI 36(45):11418–11426

    Article  Google Scholar 

  44. Wen M, Cong P, Zhang Z, Lu H, Li T (2018) Deepmirtar: a deep-learning approach for predicting human mi RNA targets. Bioinformatics 34 (22):3781–3787

    Article  Google Scholar 

  45. Wimley William C, White Stephen H (1996) Experimentally determined hydrophobicity scale for proteins at membrane interfaces. Nat Struct Biol 3(10):842–848

    Article  Google Scholar 

  46. Xie SQ, Nie P, Wang Y, Wang H, Li H, Yang Z, Liu Y, Ren J, Xie Z (2016) RPF Db: a database for genome wide information of translated m RNA generated from ribosome profiling. Nucleic Acids Res 44(D1):254–8

    Article  Google Scholar 

  47. Xuan P, Dong Y, Guo Y, Zhang T, Liu Y (2018) Dual Convolutional Neural Network Based Method for Predicting Disease-Related mi RNA s. International Journal of Molecular Science 19(12):3732

    Article  Google Scholar 

  48. Yahong H, Yi Y, Yan Y, Ma Z, Sebe N, Zhou X (2015) Semisupervised feature selection via spline regression for video semantic recognition. IEEE Trans Neural Netw Learning Syst 26(2):252–264

    Article  MathSciNet  Google Scholar 

  49. Young D, Guydosh N, Zhang F, Hinnebusch A, Green R (2015) Rli1/ ABCE 1 recycles terminating ribosomes and controls translation reinitiation in 3’ UTR s in vivo. Cell 162(4):872–884

    Article  Google Scholar 

  50. Zeng H, Edwards MD, Liu G, Gifford DK (2016) Convolutional neural network architectures for predicting DNA-protein binding. Bioinformatics 32(12):i121–i127

    Article  Google Scholar 

  51. Zhang S, Zhou JT, Hu HL, Gong H, Chen L, Cheng C, Zeng JY (2016) A deep learning framework for modeling structural features of RNA-binding protein targets. Nucleic Acids Res 44(4):e32

    Article  Google Scholar 

  52. Zhang S, Hu H, Zhou J, He X, Jiang T, Zeng J (2018) ROSE: A Deep Learning Based Framework for Predicting Ribosome Stalling Cell Systems Available at SSRN: https://ssrn.com/abstract=3155721 or https://doi.org/10.2139/ssrn.3155721

  53. Zhou ZJ (2019) Abductive learning: Towards bridging machine learning and logical reasoning. Science China Information Sciences 076101:62

    MathSciNet  Google Scholar 

  54. Zhou J, Lu Q, Xu R, Gui L, Wang H (2016) CNNsite: Prediction of DNA-binding residues in proteins using Convolutional Neural Network with sequence features 2016 IEEE international conference on bioinformatics and biomedicine, pp 78-85

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Acknowledgements

The authors are grateful to Prof. Jianyang Zeng and Dr. Hailin Hu for their help with the ideas and code of this work. The authors would like to thank Dr. Dapeng Xiong for the helpful discussions about this work. The authors would also like to thank the anonymous reviewers for their insightful comments, which greatly helped to improve the quality of this paper. This work was supported in part by the National Natural Science Foundation of China under Grants 61972333, 61802328 and 61771415, in part by the Natural Science Foundation of Hunan Province in China under Grant 2019JJ50606, in part by the Research Foundation of Education Department of Hunan Province of China under Grant 19B561, and in part by the Baidu Pinecone Program.

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Correspondence to Xieping Gao.

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Zhang, Y., Zhang, S., He, X. et al. DeepRibSt: a multi-feature convolutional neural network for predicting ribosome stalling. Multimed Tools Appl 80, 17239–17255 (2021). https://doi.org/10.1007/s11042-020-09598-8

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