journal article·2022-02-11Open access

Analyzing RNA-Seq Gene Expression Data Using Deep Learning Approaches for Cancer Classification

Laiqa Rukhsar, Waqas Haider Bangyal, Muhammad Sadiq Ali Khan, Ag Asri Ag Ibrahim, Kashif Nisar, Danda B. Rawat

Applied Sciences· Volume 12· Issue 4

Abstract

Ribonucleic acid Sequencing (RNA-Seq) analysis is particularly useful for obtaining insights into differentially expressed genes. However, it is challenging because of its high-dimensional data. Such analysis is a tool with which to find underlying patterns in data, e.g., for cancer specific biomarkers. In the past, analyses were performed on RNA-Seq data pertaining to the same cancer class as positive and negative samples, i.e., without samples of other cancer types. To perform multiple cancer type classification and to find differentially expressed genes, data for multiple cancer types need to be analyzed. Several repositories offer RNA-Seq data for various cancer types. In this paper, data from the Mendeley data repository for five cancer types are analyzed. As a first step, RNA-Seq values are converted to 2D images using normalization and zero padding. In the next step, relevant features are extracted and selected using Deep Learning (DL). In the last phase, classification is performed, and eight DL algorithms are used. Results and discussion are based on four different splitting strategies and k-fold cross validation for each DL classifier. Furthermore, a comparative analysis is performed with state of the art techniques discussed in literature. The results demonstrated that classifiers performed best at 70–30 split, and that Convolutional Neural Network (CNN) achieved the best overall results. Hence, CNN is the best DL model for classification among the eight studied DL models, and is easy to implement and simple to understand.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Genomics and Phylogenetic Studies · Molecular Biology Techniques and Applications · Machine Learning in Bioinformatics

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Computer Science, University of Gujrat, Gujrat 50700, Pakistan

Department of Computer Science, University of Karachi, Karachi 75270, Pakistan

Faculty of Computing and Informatics, University Malaysia Sabah, Kota Kinabalu 88400, Malaysia

Data Science and Cybersecurity Center, Department of Electrical Engineering and Computer Science, Howard University, Washington, DC 20059, USA

Funding

Universiti Malaysia Sabah

References (62)

Show source-provided references
1. Ali, S., Miah, S., Haque, J., Rahman, M., and Islam, K. (2021). An enhanced technique of skin cancer classification using deep convolutional neural network with transfer learning models. Mach. Learn. Appl., 5.10.1016/j.mlwa.2021.100036 ↗
2. A semi-supervised deep learning method based on stacked sparse auto-encoder for cancer prediction using RNA-seq data10.1016/j.cmpb.2018.10.004 ↗
3. Zararsiz, G., Goksuluk, D., Korkmaz, S., Eldem, V., Goksuluk, I.P., and Unver, T. (2021, July 01). MLSeq: Machine Learning Interface to RNA- Seq Data. Available online: https://bioconductor.org/packages/release/bioc/vignettes/MLSeq/inst/doc/MLSeq.pdf.
4. Waseem, Q., Alshamrani, S., Nisar, K., Din, W.W., and Alghamdi, A. (2021). Future Technology: Software-Defined Network (SDN) Forensic. Symmetry, 13.10.3390/sym13050767 ↗
5. A Comparison of Methods for RNA-Seq Differential Expression Analysis and a New Empirical Bayes Approach10.3390/bios3030238 ↗
6. Conesa, A., Madrigal, P., Tarazona, S., Gomez-Cabrero, D., Cervera, A., McPherson, A., Szcześniak, M.W., Gaffney, D.J., Elo, L.L., and Zhang, X. (2016). A survey of best practices for RNA-seq data analysis. Genome Biol., 17.10.1186/s13059-016-0881-8 ↗
7. Urda, D., Montes-Torres, J., Moreno, F., Franco, L., and Jerez, J.M. (2017, January 14–16). Deep Learning to Analyze RNA-Seq Gene Expression Data. Proceedings of the 14th International Work-Conference on Artificial Neural Networks, IWANN, Cadiz, Spain.10.1007/978-3-319-59147-6_5 ↗
8. A deep learning approach for cancer detection and relevant gene identification
9. Enhanced concept-level sentiment analysis system with expanded ontological relations for efficient classification of user reviews10.1016/j.eij.2021.03.001 ↗
10. Angra, S., and Ahuja, S. (2017). Machine Learning and Its Applications: A Review, International Conference on Big Data Analytics and Computational Intelligence (ICBDAC).10.1109/ICBDACI.2017.8070809 ↗
11. Applications of machine learning and rule induction10.1145/219717.219768 ↗
12. Memon, S.K., Nisar, K., Hijazi, M.H.A., Chowdhry, B.S., and Sodhro, A.H. (2021). A Survey on 802.11 MAC Industrial Standards, Architecture, Security & Supporting Emergency Traffic: Future Directions. J. Ind. Inf. Integr. Elsevier, in press.10.1016/j.jii.2021.100225 ↗
13. Gad, A.F. (2018). Practical Computer Vision Applications Using Deep Learning with CNNs with Detailed Examples in Python Using TensorFlow and Kivy, Apress. [1st ed.].10.1007/978-1-4842-4167-7 ↗
14. Au-tomated controller placement for software-defined networks to resist ddos attacks
15. Cao, J., Wu, C., Chen, L., Cui, H., and Feng, G. (2019). An Improved Convolutional Neural Network Algorithm and Its Application in Multilabel Image Labeling. Comput. Intell. Neurosci., 2019.10.1155/2019/2060796 ↗
16. De Guia, J.M., Devaraj, M., and Leung, C.K. (2019, January 27–30). DeepGX: Deep learning using gene expression for cancer classification. Proceedings of the 2019 IEEE/ACM International Conference on Advances in Social Networks Analysis and Mining, ASONAM, Vancouver, BC, Canada.10.1145/3341161.3343516 ↗
17. Guillen, P., and Ebalunode, J. (2016, January 15–17). Cancer Classification Based on Microarray Gene Expression Data Using Deep Learning. Proceedings of the 2016 International Conference on Computational Science and Computational Intelligence (CSCI), Las Vegas, NV, USA.10.1109/CSCI.2016.0270 ↗
18. Nisar, K., Sabir, Z., Raja, M.Z., Ibrahim, A.A., Rodrigues, J., Khan, A.S., Gupta, M., Kamal, A., and Rawat, D. (2021). Evolutionary Integrated Heuristic with Gudermannian Neural Networks for Second Kind of Lane–Emden Nonlinear Singular Models. Appl. Sci., 11.10.3390/app11114725 ↗
19. Deep learning for inferring gene relationships from single-cell expression data10.1073/pnas.1911536116 ↗
20. Design of Morlet Wavelet Neural Network for Solving a Class of Singular Pantograph Nonlinear Differential Models10.1109/ACCESS.2021.3072952 ↗
21. A New Estimation of Nonlinear Contact Forces of Railway Vehicle10.32604/iasc.2021.016990 ↗
22. Lyu, B., and Haque, A. (2018, January 11). Deep Learning Based Tumor Type Classification Using Gene Expression Data. Proceedings of the 2018 ACM International Conference on Bioinformatics, Computational Biology, and Health Informatics, Washington, DC, USA.10.1145/3233547.3233588 ↗
23. Optimisation of cancer classification by machine learning generates an enriched list of candidate drug targets and biomarkers10.1039/C9MO00198K ↗
24. A deep learning-based multi-model ensemble method for cancer prediction10.1016/j.cmpb.2017.09.005 ↗
25. MLSeq: Machine learning interface for RNA-sequencing data10.1016/j.cmpb.2019.04.007 ↗
26. Using machine learning and high-throughput RNA sequencing to classify the precursors of small non-coding RNAs10.1016/j.ymeth.2013.10.002 ↗
27. Artificial Intelligence Technique for Gene Expression by Tumor RNA-Seq Data: A Novel Optimized Deep Learning Approach10.1109/ACCESS.2020.2970210 ↗
28. Hassanzadeh, H.R., Phan, J.H., and Wang, M.D. (2017, January 28–29). A Multi-Modal Graph-Based Semi-Supervised Pipeline for Predicting Cancer Survival Hamid. Proceedings of the Modern Artificial Intelligence and Cognitive Science Conference (MAICS), Fort Wayne, IN, USA.10.1109/BIBM.2016.7822516 ↗
29. Wu, J., and Hicks, C. (2021). Breast Cancer Type Classification Using Machine Learning. J. Pers. Med., 11.10.3390/jpm11020061 ↗
30. Tranchevent, L.-C., Azuaje, F., and Rajapakse, J.C. (2019). A deep neural network approach to predicting clinical outcomes of neuroblastoma patients. BMC Med. Genom., 12.10.1186/s12920-019-0628-y ↗
31. McDermaid, A., Chen, X., Zhang, Y., Wang, C., Gu, S., Xie, J., and Ma, Q. (2018). A New Machine Learning-Based Framework for Mapping Uncertainty Analysis in RNA-Seq Read Alignment and Gene Expression Estimation. Front. Genet., 9.10.3389/fgene.2018.00313 ↗
32. Sodhro, A.H., Al-Rakhami, M.S., Wang, L., Magsi, H., Zahid, N., Pirbhulal, S., Nisar, K., and Ahmad, A. (2021, January 25–28). Decentralized Energy Efficient Model for Data Transmission in IoT-based Healthcare System. Proceedings of the 2021 IEEE 93rd Vehicular Technology Conference (VTC2021-Spring), Helsinki, Finland.10.1109/VTC2021-Spring51267.2021.9448886 ↗
33. Chowdhry, B., Shah, A.A., Harris, N., Hussain, T., and Nisar, K. (2020, January 7–10). Development of a Smart Instrumentation for Analyzing Railway Track Health Monitoring Using Forced Vibration. Proceedings of the 2020 IEEE 14th International Conference on Application of Information and Communication Technologies (AICT), Tashkent, Uzbekistan.10.1109/AICT50176.2020.9368670 ↗
34. Nisar, K., Lawal, I.A., Abdulmalik, U.I., Mu’Azu, A.A., Chowdhry, B., Khan, S., and Memon, S. (2020, January 7–10). QoS Analysis of the MANET routing protocols with Respect to Delay, Throughput, & Network load: Challenges and Open Issues. Proceedings of the 2020 IEEE 14th International Conference on Application of Information and Communication Technologies (AICT), Tashkent, Uzbekistan.10.1109/AICT50176.2020.9368835 ↗
35. Nisar, K., Jimson, E.R., Hijazi, M.H.B.A., Ibrahim, A.A.A., Park, Y.-J., and Welch, I. (2019, January 23–25). A New Bandwidth Management Model using Software-Defined Networking Security Threats. Proceedings of the 2019 IEEE 13th International Conference on Application of Information and Communication Technologies (AICT), Baku, Azerbaijan.10.1109/AICT47866.2019.8981784 ↗
36. Nisar, K., Ibrahim, A.A.A., Park, Y.-J., Hzou, Y.K., Memon, S.K., Naz, N., and Welch, I. (2019, January 19). Indoor Roaming Activity Detection and Analysis of Elderly People using RFID Technology. Proceedings of the 2019 1st International Conference on Artificial Intelligence and Data Sciences (AiDAS), Perak, Malaysia.10.1109/AiDAS47888.2019.8970780 ↗
37. Ali, N.F., Said, A.M., Nisar, K., and Aziz, I.A. (2017, January 13–14). A survey on software defined network approaches for achieving energy efficiency in wireless sensor network. Proceedings of the 2017 IEEE Conference on Wireless Sensors (ICWiSe), Miri, Malaysia.10.1109/ICWISE.2017.8267157 ↗
38. Salam, N., Abbas, M.K., Maheshwari, M.K., Chowdhry, B., and Nisar, K. (2021, January 9–12). Future Mobile Technology: Channel Access Mechanism for LTE-LAA using Deep Learning. Proceedings of the 2021 IEEE 18th Annual Consumer Communications & Networking Conference (CCNC), Las Vegas, NV, USA.10.1109/CCNC49032.2021.9369598 ↗
39. Nisar, K., Mu’Azu, A.A., Lawal, I.A., Khan, S., and Memon, S. (2020, January 7–10). Reliable Priority Based QoS Real-Time Traffic Routing in VANET: Open Issues & Parameter. Proceedings of the 2020 IEEE 14th International Conference on Application of Information and Communication Technologies (AICT), Tashkent, Uzbekistan.10.1109/AICT50176.2020.9368689 ↗
40. A machine learning method for the discovery of minimum marker gene combinations for cell type identification from single-cell RNA sequencing10.1101/gr.275569.121 ↗
41. Guo, Y., Liu, S., Li, Z., and Shang, X. (2017, January 13–16). Towards the classification of cancer subtypes by using cascade deep forest model in gene expression data. Proceedings of the 2017 IEEE International Conference on Bioinformatics and Biomedicine (BIBM), Kansas City, MO, USA.10.1109/BIBM.2017.8217909 ↗
42. Ferles, C., and Naidoo, K. (2021, July 06). Cancer Types: RNA Sequencing Values from Tumor Samples/Tissues. Available online: https://data.mendeley.com/datasets/sf5n64hydt/1.
43. Feng, T., Zhang, P., Sun, Y., Han, X., Tong, J., and Hua, Z. (2020). Evaluation of the Role of hsa-mir-124 in Predicting Clinical Outcome in Breast Invasive Carcinoma Based on Bioinformatics Analysis. BioMed Res. Int., 2020.10.1155/2020/1839205 ↗
44. Coexistence of phylloides tumour and invasive ductal cancer in the breast10.4103/njcp.njcp_602_18 ↗
45. Zhan, Y., Guo, W., Zhang, Y., Wang, Q., Xu, X.-J., and Zhu, L. (2015). A Five-Gene Signature Predicts Prognosis in Patients with Kidney Renal Clear Cell Carcinoma. Comput. Math. Methods Med., 2015.10.1155/2015/842784 ↗
46. The Complex Roles of MicroRNAs in the Metastasis of Renal Cell Carcinoma10.1166/jnn.2013.6712 ↗
47. Anusewicz, D., Orzechowska, M., and Bednarek, A.K. (2020). Lung squamous cell carcinoma and lung adenocarcinoma differential gene expression regulation through pathways of Notch, Hedgehog, Wnt, and ErbB signalling. Sci. Rep., 10.10.1038/s41598-020-77284-8 ↗
48. Zhou, C., Li, C., Yan, F., and Zheng, Y. (2020). Identification of an immune gene signature for predicting the prognosis of patients with uterine corpus endometrial carcinoma. Cancer Cell Int., 20.10.1186/s12935-020-01560-w ↗
49. Treatment strategies for endometrial cancer: Current practice and perspective10.1097/GCO.0000000000000338 ↗
50. Żejmo, M., Kowal, M., Korbicz, J., and Monczak, R. (2017). Classification of breast cancer cytological specimen using convolutional neural network. J. Phys. Conf. Ser., 783.10.1088/1742-6596/783/1/012060 ↗
51. Optimization of Neural Network Using Improved Bat Algorithm for Data Classification10.1166/jmihi.2019.2654 ↗
52. A forward only counter propagation network-based approach for contraceptive method choice classification task10.1080/0952813X.2011.639091 ↗
53. Feng, V. (2021, August 01). An Overview of ResNet and Its Variants. Available online: https://towardsdatascience.com/an-overview-of-resnet-and-its-variants-5281e2f56035.
54. Bangyal, W.H., Ahmad, J., Rauf, H.T., and Shakir, R. (2018, January 18–20). Evolving Artificial Neural Networks Using Opposition Based Particle Swarm Optimization Neural Network for Data Classification. Proceedings of the 2018 International Conference on Innovation and Intelligence for Informatics, Computing, and Technologies (3ICT), Sakhier, Bahrain.10.1109/3ICT.2018.8855772 ↗
55. Forward Stability of ResNet and Its Variants10.1007/s10851-019-00922-y ↗
56. Deep Learning in Image Classification using Residual Network (ResNet) Variants for Detection of Colorectal Cancer10.1016/j.procs.2021.01.025 ↗
57. Early detection of breast cancer using hybrid of series network and VGG-1610.1007/s11042-020-09914-2 ↗
58. Alake, R. (2021, July 08). Deep Learning: GoogLeNet Explained. Available online: https://towardsdatascience.com/deep-learning-googlenet-explained-de8861c82765.
59. Bangyal, W.H., Hameed, A., Alosaimi, W., and Alyami, H. (2021). A New Initialization Approach in Particle Swarm Optimization for Global Optimization Problems. Comput. Intell. Neurosci., 2021.10.1155/2021/6628889 ↗
60. Titoriya, A., and Sachdeva, S. (2019, January 21). Breast Cancer Histopathology Image Classification using AlexNet. Proceedings of the 2019 4th International Conference on Information Systems and Computer Networks (ISCON), Mathura, India.10.1109/ISCON47742.2019.9036160 ↗
61. (2021, December 02). DAVID Functional Annotation Bioinformatics Microarray Analysis, Available online: https://david.ncifcrf.gov/.
62. Zhou, H., Jin, J., Zhang, H., Yi, B., Wozniak, M., and Wong., L. (2012). IntPat—An integrated pathway gene relationship database for model organisms and important pathogens. BMC Syst. Biol., 6.10.1186/1752-0509-6-S2-S2 ↗