Generic placeholder image

Current Bioinformatics

Editor-in-Chief

ISSN (Print): 1574-8936
ISSN (Online): 2212-392X

Research Article

ConvChrome: Predicting Gene Expression Based on Histone Modifications Using Deep Learning Techniques

Author(s): Rania Hamdy*, Fahima A. Maghraby* and Yasser M.K. Omar

Volume 17, Issue 3, 2022

Published on: 28 March, 2022

Page: [273 - 283] Pages: 11

DOI: 10.2174/1574893616666211214110625

Price: $65

Abstract

Background: Gene regulation is a complex and dynamic process that not only depends on the DNA sequence of genes but is also influenced by a key factor called epigenetic mechanisms. This factor, along with other factors, contributes to changing the behavior of DNA. While these factors cannot affect the structure of DNA, they can control the behavior of DNA by turning genes "on" or "off," which determines which proteins are transcribed.

Objectives: This paper will focus on the histone modification mechanism; histones are the group of proteins that bundle the DNA into a structural form called nucleosomes (coils); The way these histone proteins wrap DNA determines whether or not a gene can be accessed for expression. When histones are tightly bound to DNA, the gene is unable to be expressed, and vice versa. It is important to know histone modifications’ combinatorial patterns and how these combinatorial patterns can affect and work together to control the process of gene expression.

Methods: In this paper, ConvChrome deep learning methodologies are proposed for predicting the gene expression behavior from histone modifications data as an input to use more than one convolutional network model; this happens in order to recognize patterns of histones signals and interpret their spatial relationship on chromatin structure to give insights into regulatory signatures of histone modifications.

Results and Conclusion: The results show that ConvChrome achieved an Area Under the Curve (AUC) score of 88.741%, which is an outstanding improvement over the baseline for gene expression classification prediction task from combinatorial interactions among five histone modifications on 56 different cell types

Keywords: Epigenetics, gene expression regulation, histone modifications, deep learning, DNA, convolution neural networks.

Graphical Abstract

[1]
Reik W. Stability and flexibility of epigenetic gene regulation in mammalian development. Nature 2007; 447(7143): 425-32.
[http://dx.doi.org/10.1038/nature05918] [PMID: 17522676]
[2]
Hoopes L. Introduction to the gene expression and regulation topic room. Nat Edu 2008; 1(1): 160. Available from:.https://www.nature.com/scitable/topic/gene-expression-and-regulation-15/
[3]
Morgan HD, Santos F, Green K, Dean W, Reik W. Epigenetic reprogramming in mammals. Hum Mol Genet 2005; 14(Spec No 1)(Suppl. 1): R47-58.
[http://dx.doi.org/10.1093/hmg/ddi114] [PMID: 15809273]
[4]
Bannister AJ, Kouzarides T. Regulation of chromatin by histone modifications. Cell Res 2011; 21(3): 381-95.
[http://dx.doi.org/10.1038/cr.2011.22] [PMID: 21321607]
[5]
Görisch SM, Wachsmuth M, Tóth KF, Lichter P, Rippe K. Histone acetylation increases chromatin accessibility. J Cell Sci 2005; 118(Pt 24): 5825-34.
[http://dx.doi.org/10.1242/jcs.02689] [PMID: 16317046]
[6]
Lawrence M, Daujat S, Schneider R. Lateral thinking: How histone modifications regulate gene expression. Trends Genet 2016; 32(1): 42-56.
[http://dx.doi.org/10.1016/j.tig.2015.10.007] [PMID: 26704082]
[7]
Nativio R, Lan Y, Donahue G, et al. An integrated multi-omics approach identifies epigenetic alterations associated with alzheimer’s dis-ease. Nat Genet 2020; 52(10): 1024-35.
[http://dx.doi.org/10.1038/s41588-020-0696-0] [PMID: 32989324]
[8]
Girdhar K, Hoffman GE, Jiang Y, et al. Cell-specific histone modification maps in the human frontal lobe link schizophrenia risk to the neuronal epigenome. Nat Neurosci 2018; 21(8): 1126-36.
[http://dx.doi.org/10.1038/s41593-018-0187-0] [PMID: 30038276]
[9]
Narin A, Kaya C, Pamuk Z. Automatic detection of coronavirus disease (COVID-19) using X-ray images and deep convolutional neural networks. Pattern Anal Appl 2021. [Epub ahead of print
[PMID: 33994847]
[10]
Affonso C, Rossi AL, Vieira FH, de Leon Ferreira AC. Deep learning for biological image classification. Expert Syst Appl 2017; 85: 114-22.
[http://dx.doi.org/10.1016/j.eswa.2017.05.039]
[11]
Pattarone G, Acion L, Simian M, Iarussi E. Learning deep features for dead and living breast cancer cell classification without staining. Sci Rep 2021; 11(1): 10304.
[PMID: 33414495]
[12]
Abbaschian BJ, Sierra-Sosa D, Elmaghraby A. Deep learning techniques for speech emotion recognition, from databases to models. Sensors (Basel) 2021; 21(4): 1249.
[http://dx.doi.org/10.3390/s21041249] [PMID: 33578714]
[13]
Digan W, Névéol A, Neuraz A, et al. Can reproducibility be improved in clinical natural language processing? A study of 7 clinical NLP suites. J Am Med Inform Assoc 2021; 28(3): 504-15.
[http://dx.doi.org/10.1093/jamia/ocaa261] [PMID: 33319904]
[14]
Ndikumana A, Tran NH, Kim KT, Hong CS. Deep learning based caching for self-driving cars in multi-access edge computing. IEEE Trans Intell Transp Syst 2020; 22(5): 2862-77.
[http://dx.doi.org/10.1109/TITS.2020.2976572]
[15]
Kouris A, Venieris SI, Rizakis M, Bouganis CS. Approximate LSTMs for time-constrained inference: Enabling fast reaction in self-driving cars. IEEE Consum Electron Mag 2020; 9(4): 11-26.
[http://dx.doi.org/10.1109/MCE.2020.2969195]
[16]
Sun M, Zhao S, Gilvary C, Elemento O, Zhou J, Wang F. Graph convolutional networks for computational drug development and discov-ery. Brief Bioinform 2020; 21(3): 919-35.
[http://dx.doi.org/10.1093/bib/bbz042] [PMID: 31155636]
[17]
Islam MM, Karray F, Alhajj R, Zeng J. A review on deep learning techniques for the diagnosis of novel coronavirus (COVID-19). IEEE Access 2021; 9: 30551-72.
[http://dx.doi.org/10.1109/ACCESS.2021.3058537]
[18]
Strodthoff N, Wagner P, Wenzel M, Samek W. UDSMProt: Universal deep sequence models for protein classification. Bioinformatics 2020; 36(8): 2401-9.
[http://dx.doi.org/10.1093/bioinformatics/btaa003] [PMID: 31913448]
[19]
Jo T, Hou J, Eickholt J, Cheng J. Improving protein fold recognition by deep learning networks. Sci Rep 2015; 5(1): 17573.
[http://dx.doi.org/10.1038/srep17573] [PMID: 26634993]
[20]
Chen Y, Li Y, Narayan R, Subramanian A, Xie X. Gene expression inference with deep learning. Bioinformatics 2016; 32(12): 1832-9.
[http://dx.doi.org/10.1093/bioinformatics/btw074] [PMID: 26873929]
[21]
LeCun Y, Bottou L, Bengio Y, Haffner P. Gradient-based learning applied to document recognition. Proc IEEE 1998; 86(11): 2278-324.
[http://dx.doi.org/10.1109/5.726791]
[22]
Goodfellow I, Bengio Y, Courville A. Deep learning (adaptive computation and machine learning series). Cambridge Massachusetts. 2017; pp. 321-59.
[23]
Cai S, Shu Y, Chen G, Ooi BC, Wang W, Zhang M. Effective and efficient dropout for deep convolutional neural networks. Machine Learn 2019; 2019: 1904.03392.
[24]
Rectifier (neural networks). 2020 2020. Available from: https://en.wikipedia.org/wiki/Rectifier_(neural_networks)
[25]
Yu D, Wang H, Chen P, Wei Z. Mixed pooling for convolutional neural networks. In: Lecture Notes in Computer Science. Cham: Springer 2014.
[26]
Srivastava N, Hinton G, Krizhevsky A, Sutskever I, Salakhutdinov R. Dropout: A simple way to prevent neural networks from overfitting. J Mach Learn Res 2014; 15(1): 1929-58.
[27]
Vaswani A, Shazeer N, Parmar N, et al. Attention is all you need. In: Advances in neural information processing systems. UK: MIT Press 2017; pp. 5998-6008.
[28]
Cheng C, Yan KK, Yip KY, et al. A statistical framework for modeling gene expression using chromatin features and application to modENCODE datasets. Genome Biol 2011; 12(2): R15.
[http://dx.doi.org/10.1186/gb-2011-12-2-r15] [PMID: 21324173]
[29]
Dong X, Greven MC, Kundaje A, et al. Modeling gene expression using chromatin features in various cellular contexts. Genome Biol 2012; 13(9): R53.
[http://dx.doi.org/10.1186/gb-2012-13-9-r53] [PMID: 22950368]
[30]
Sun S, Sun X, Zheng Y. Higher-order partial least squares for predicting gene expression levels from chromatin states. BMC Bioinformatics 2018; 19(5): 113.
[http://dx.doi.org/10.1186/s12859-018-2100-y] [PMID: 29671394]
[31]
Singh R, Lanchantin J, Robins G, Qi Y. DeepChrome: Deep-learning for predicting gene expression from histone modifications. Bioinformatics 2016; 32(17): i639-48.
[http://dx.doi.org/10.1093/bioinformatics/btw427] [PMID: 27587684]
[32]
Singh R, Lanchantin J, Sekhon A, Qi Y. Attend and predict: Understanding gene regulation by selective attention on chromatin. Adv Neural Inf Process Syst 2017; 30: 6785-95.
[PMID: 30147283]
[33]
Zhu L, Kesseli J, Nykter M, Huttunen H. Predicting gene expression levels from histone modification signals with convolutional recurrent neural networksInEMBEC & NBC. Singapore: Springer 2017; pp. 555-8.
[34]
Chaubey V, Nair MS, Pillai GN. Gene expression prediction using a deep 1d convolution neural network. In: IEEE Symposium Series on Computational Intelligence (SSCI).
[http://dx.doi.org/10.1109/SSCI44817.2019.9002669]
[35]
Kamal IM, Wahid NA, Bae H. Gene expression prediction using stacked temporal convolutional network. In: IEEE International Conference on Big Data and Smart Computing (BigComp) 17-20 Jan. Busan, Korea. 2021.
[http://dx.doi.org/10.1109/BigComp48618.2020.00-41]
[36]
Cheng W, Murtaza G, Wang A. SimpleChrome: Encoding of combinatorial effects for predicting gene expression. Machine Learn 2020; 2020: 08671.
[37]
Symeonidi A, Nicolaou A, Johannes F, Christlein V. Recursive Convolutional Neural Networks for Epigenomics. In: 25th International Conference on Pattern Recognition (ICPR) 10-15 Jan. Milan, Italy 2021.
[38]
Kingma DP, Ba J. Adam: A method for stochastic optimization. Machine Learn 2014; 2014: 1412.6980..
[39]
Kundaje A, Meuleman W, Ernst J, et al. Integrative analysis of 111 reference human epigenomes. Nature 2015; 518(7539): 317-0.
[http://dx.doi.org/10.1038/nature14248] [PMID: 25693563]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy