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Identification of RNA Pseudouridine Sites using Deep Learning Approaches

Supervised By

Dr. Md. Al Mamun

Professor

Dept. of Computer Science & Engineering

Rajshahi University of Engineering & Technology

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Presented By

Abu Zahid Bin Aziz

Roll: 1503047

Dept. of Computer Science & Engineering

Rajshahi University of Engineering & Technology

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Outline

  • Introduction
  • Motivation
  • Objectives
  • Literature Review
  • Workflow
  • Dataset collection
  • Data preprocessing
  • Architecture of our CNN model
  • Hyperparameter tuning
  • Results
  • Webserver Implementation
  • Future scope
  • Publication
  • References

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Introduction

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  • Pseudouridine (Ψ) is the most prevalent RNA modification found in both prokaryotes and eukaryotes.
  • They have been confirmed to occur in rRNA, mRNA, tRNA, and nuclear/nucleolar RNA.
  • Identifying them has vital significance in drug development, gene therapy, academic research etc.
  • In this work, we proposed a multi-stage convolutional neural network for identifying Ψ-sites.

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  • Previous predictors that were developed using laboratory techniques had some demerits such as-
    • Costly
    • Time consuming
    • Required experienced professionals for maintenance.

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  • These problems encouraged us for applying computational methods in this task.

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Motivation

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  • To find an effective computational method to identify Pseudouridine sites.
  • To investigate CNN’s performance on biological sequence inputs.
  • To investigate whether multi-stage CNN model can produce better result than a sequential CNN model.
  • To employ a CNN model which will produce better performances than the existing ones.

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Objectives

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  • Ppus(2015): SVM classifier by Li et al.[1]
  • iRNA-Pseu(2016): Improved from previous classifier by Chen et al.[2]
  • PseUI(2018): SVM classifier by He et al.[3]
  • iPseu-CNN(2019): CNN classifier by Tahir et al.[4]
  • XG-Pseu(2019): Gradient boosting based method Liu et al.[5]
  • iPseu-Layer(2020): An ensemble model Mu et al. [6]

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Literature Review

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Workflow

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  • Data were collected for three different species which are H. sapience, S. cerevisiae and M. musculus.

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Species

Benchmark Samples

Independent samples

Length of Nucleotides

H. Sapiens(HS)

990

200

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S. Cerevisiae(SC)

628

200

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M. Musculus(MM)

944

None

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Dataset Collection

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  • Our data preprocessing had only one step- Binary ‘one-hot’ encoding.
  • We did it in two ways:
    • General ‘one-hot’ encoding
    • Merged-seq ‘one-hot’ encoding
  • General ‘one-hot’ encoding converted the inputs into (N, 4) matrix.

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Data Preprocessing

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  • Merged-seq ‘one-hot’ encoding converted our inputs into (N, 12) matrix.

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Data Preprocessing(Contd.)

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CNN Architecture(General)

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CNN Architecture(Multi-stage)

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  • In our investigation we tuned a number of hyperparameters.
  • We employed k-fold cross-validation(k=10) and grid search for that.

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Hyperparameters

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Ranges of Values

Datasets

HS_990, MM_944

SC_628

Batch Size

[10,20,30,40]

10

10

No. of Epochs

[10,50,100,200]

100

100

No. of Channels

[5,7,9,10,11]

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Filter Height

[3,5,7,9]

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Learning Rate

[0.001,0.0003,0.0005,0.00057,0.0001]

0.0005

0.0001

Dropout Probability

[0.4,0.45,0.5,0.55,0.6]

0.6

0.4

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Hyperparameter Tuning

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Hyperparameter Tuning(Contd.)

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Predictors

Independent Datasets

S_200

H_200

AC(%)

SN(%)

SP(%)

MCC

AC(%)

SN(%)

SP(%)

MCC

iRNA-Pseu[2]

60.00

63.00

57.00

0.20

61.50

58.00

65.00

0.23

PseUI[3]

68.50

65.00

72.00

0.37

65.50

63.00

68.00

0.31

iPseu-CNN[4]

73.50

68.76

77.42

0.47

69.00

77.72

60.81

0.40

iPseu-Layer[6]

72.50

68.00

77.00

0.45

71.00

63.00

79.00

0.43

Ours(General)

75.00

67.00

83.00

0.50

72.5

80.00

65.00

0.44

Ours (Merged-seq)

76.50

80.00

73.00

0.53

74.00

73.00

75.00

0.48

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Results

*AC= ACCURACY, SN=SENSITIVITY, SP=SPECIFICITY, MCC= MATTHEWS CORRELATION COEFFICIENT

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Results(Contd.)

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Results(Contd.)

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Webserver Implementation(Step-1)

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Webserver Implementation(Step-2)

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  • Taking account of RNAs of other species.
  • Taking account of other RNA modifications.
  • Investigating CNN’s performance in other biological datasets.
  • Implementing other encoding techniques.

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Future Scopes

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  • Based on the findings of our work, a paper was accepted and presented in the iEEE Region 10 Symposium (TENSYMP) 2020.
  • The paper is available in the iEEE Xplore digital library. �

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Publication

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[1] Y.-H. Li, G. Zhang, and Q. Cui, “Ppus: a web server to predict pusspecific pseudouridine sites,” Bioinformatics, vol. 31, no. 20, pp. 3362–3364, 2015.

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[2] W. Chen, H. Tang, J. Ye, H. Lin, and K.-C. Chou, “iRNA-Pseu: Identifying rna pseudouridine sites,” Molecular Therapy-Nucleic Acids, vol. 5, p.e332, 2016.

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[3] J. He, T. Fang, Z. Zhang, B. Huang, X. Zhu, and Y. Xiong, “PseUI: pseudouridine sites identification based on rna sequence information,” BMC bioinformatics, vol. 19, no. 1, p. 306, 2018.

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[4] M. Tahir, H. Tayara, and K. T. Chong, “iPseU-CNN: Identifying RNA pseudouridine sites using convolutional neural networks,” Molecular Therapy-Nucleic Acids, vol. 16, pp. 463–470, 2019.

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[5] Liu K, Chen W, Lin H. XG-PseU: an eXtreme Gradient Boosting based method for identifying pseudouridine sites. Molecular Genetics and Genomics. 2020;295(1):13–21.

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[6] Mu Y, Zhang R, Wang L, Liu X. iPseU-Layer: Identifying RNA Pseudouridine Sites Using Layered Ensemble Model. Interdisciplinary Sciences: Computational Life Sciences. 2020; p. 1–11.

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References

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Thank You