Skip to main content

Advertisement

Log in

Fine-tuning-based Transfer Learning for Characterization of Adeno-Associated Virus

  • Published:
Journal of Signal Processing Systems Aims and scope Submit manuscript

Abstract

Accurate and precise identification of adeno-associated virus (AAV) vectors play an important role in dose-dependent gene therapy. Although solid-state nanopore techniques can potentially be used to characterize AAV vectors by capturing ionic current, the existing data analysis techniques fall short of identifying them from their ionic current profiles. Recently introduced machine learning methods such as deep convolutional neural network (CNN), developed for image identification tasks, can be applied for such classification. However, with smaller data set for the problem in hand, it is not possible to train a deep neural network from scratch for accurate classification of AAV vectors. To circumvent this, we applied a pre-trained deep CNN (GoogleNet) model to capture the basic features from ionic current signals and subsequently used fine-tuning-based transfer learning to classify AAV vectors. The proposed method is very generic as it requires minimal preprocessing and does not require any handcrafted features. Our results indicate that fine-tuning-based transfer learning can achieve an average classification accuracy between 90 and 99% in three realizations with a very small standard deviation. Results also indicate that the classification accuracy depends on the applied electric field (across nanopore) and the time frame used for data segmentation. We also found that the fine-tuning of the deep network outperforms feature extraction-based classification for the resistive pulse dataset. To expand the usefulness of the fine-tuning-based transfer learning, we have tested two other pre-trained deep networks (ResNet50 and InceptionV3) for the classification of AAVs. Overall, the fine-tuning-based transfer learning from pre-trained deep networks is very effective for classification, though deep networks such as ResNet50 and InceptionV3 take significantly longer training time than GoogleNet.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8

Similar content being viewed by others

Availability of Data and Material

All data associated with this paper is publicly available at https://github.com/mstfwsulab/AAV-classification.

Code Availability

All codes are available upon request.

References

  1. Li, C., & Samulski, R. J. (2020). Engineering adeno-associated virus vectors for gene therapy. Nature Reviews Genetics, 21(4), 255–272

    Article  Google Scholar 

  2. FlotteT. R., Afione, S. A., Conrad, C., McGrath, S. A., Solow, R., Oka, H., Zeitlin, P. L., Guggino, W. B., & Carter, B. J. F. (1993). Stable in vivo expression of the cystic fibrosis transmembrane conductance regulator with an adeno-associated virus vector. Proceedings of the National Academy of Sciences, 90(22), 10613–10617

    Article  Google Scholar 

  3. Li, C., Bowles, D. E., van Dyke, T., & Samulski, R. J. (2005). Adeno-associated virus vectors: Potential applications for cancer gene therapy. Cancer Gene Therapy, 12(12), 913–925

    Article  Google Scholar 

  4. Naso, M. F., Tomkowicz, B., Perry, W. L., & Strohl, W. R. (2017). Adeno-Associated Virus (AAV) as a vector for gene therapy. BioDrugs, 31(4), 317–334

    Article  Google Scholar 

  5. Gimpel, A. L., Katsikis, G., Sha, S., Maloney, A. J., Hong, M. S., Nguyen, T. N. T., Wolfrum, J., Springs, S. L., Sinskey, A. J., Manalis, S. R., Barone, P. W., & Braatz, R. D. (2021). Analytical methods for process and product characterization of recombinant adeno-associated virus-based gene therapies. Molecular Therapy-Methods & Clinical Development, 20, 740–754

    Article  Google Scholar 

  6. Lock, M., McGorray, S., Auricchio, A., Ayuso, E., Beecham, E. J., Blouin-Tavel, V., Bosch, F., Bose, M., Byrne, B. J., Caton, T., Chiorini, J. A., Chtarto, A., Clark, K. R., Conlon, T., Darmon, C., Doria, M., Douar, A., Flotte, T. R., Francis, J. D., & Snyder, R. O. (2010). Characterization of a recombinant adeno-associated virus type 2 reference standard material. Human Gene Therapy, 21(10), 1273–1285

    Article  Google Scholar 

  7. Fried, J. P., Swett, J. L., Nadappuram, B. P., Mol, J. A., Edel, J. B., Ivanov, A. P., & Yates, J. R. (2021). In situ solid-state nanopore fabrication. Chemical Society Reviews, 50(8), 4974–4992

    Article  Google Scholar 

  8. Karawdeniya, B. I., Bandara, Y., Khan, A. I., Chen, W. T., Vu, H. A., Morshed, A., Suh, J., Dutta, P., & Kim, M. J. (2020). Adeno-associated virus characterization for cargo discrimination through nanopore responsiveness. Nanoscale, 12(46), 23721–23731

    Article  Google Scholar 

  9. Marques, A. D., Kummer, M., Kondratov, O., Banerjee, A., Moskalenko, O., & Zolotukhin, S. (2021). Applying machine learning to predict viral assembly for adeno-associated virus capsid libraries. Molecular Therapy-Methods & Clinical Development, 20, 276–286

    Article  Google Scholar 

  10. Krizhevsky, A., Sutskever, I., & Hinton, G. E. (2012). Imagenet classification with deep convolutional neural networks. Proc. Advances in Neural Information Processing Systems, 25, 1097–1105

    Google Scholar 

  11. Simonyan, K., & Zisserman, A. (2014). Very deep convolutional networks for large-scale image recognition, arXiv preprint arXiv:1409.1556

  12. Zeiler M. D., & Fergus, R. (2014). Visualizing and understanding convolutional networks. In: Fleet D., Pajdla T., Schiele B., Tuytelaars T. (eds) Computer Vision – ECCV 2014. ECCV 2014. Lecture Notes in Computer Science, vol 8689. Springer, Cham. https://doi.org/10.1007/978-3-319-10590-1_53

  13. Szegedy, C., Liu, W., Jia, Y., Sermanet, P., Reed, S., Anguelov, D., Erhan, D., Vanhoucke, V., & Rabinovich, A. (2015). Going deeper with convolutions. Proceedings of the IEEE Conference on Computer Vision and Pattern Recognition, 1–9

  14. He, K. M., Zhang, X. Y., Ren, S. Q., Sun, J., & IEEE. (2016). Deep residual learning for image recognition. Proc. IEEE Conference on Computer Vision and Pattern Recognition (CVPR), 2016, 770–778

    Google Scholar 

  15. Xiao, Z. W., Xu, X., Xing, H. L., Qu, R., Song, F. H., & Zhao, B. W. (2021). IEEE RNTS: Robust neural temporal search for time series classification. Proceedings of International Joint Conference on Neural Networks (IJCNN), 1–8

  16. Xiao, Z. W., Xu, X., Zhang, H. X., & Szczerbicki, E. (2021). A new multi-process collaborative architecture for time series classification. Knowledge-Based Systems, 220, 106934

  17. Xiao, Z. W., Xu, X., Xing, H. L., Luo, S. X., Dai, P. L., & Zhan, D. W. (2021). RTFN: A robust temporal feature network for time series classification,". Information Sciences, 571, 65–86

    Article  MathSciNet  Google Scholar 

  18. LeCun, Y., Bengio, Y., & Hinton, G. (2015). Deep learning. Nature, 521(7553), 436–444

    Article  Google Scholar 

  19. Xu, Y., Mo, T., Feng, Q., Zhong, P., Lai, M., Eric, I., & Chang, C. (2014). Deep learning of feature representation with multiple instance learning for medical image analysis. Proc. 2014 IEEE international conference on acoustics, speech and signal processing (ICASSP), IEEE, 1626–1630

  20. Pärnamaa, T., & Parts, L. (2017). Accurate classification of protein subcellular localization from high-throughput microscopy images using deep learning. G3: Genes, Genomes, Genetics, 7(5), 1385–1392

  21. Nanni, L., Ghidoni, S., & Brahnam, S. (2017). Handcrafted vs. non-handcrafted features for computer vision classification. Pattern Recognition, 71, 158–172

    Article  Google Scholar 

  22. Pan, S. J., & Yang, Q. A. (2010). A survey on transfer learning. IEEE Transactions on Knowledge and Data Engineering, 22(10), 1345–1359

    Article  Google Scholar 

  23. Weiss, K., Khoshgoftaar, T. M., & Wang, D. (2016). A survey of transfer learning. Journal of Big data, 3(1), 9

    Article  Google Scholar 

  24. Tan, C. Q., Sun, F. C., Kong, T., Zhang, W. C., Yang, C., & Liu, C. F. (2018). A survey on deep transfer learning. Artificial Neural Networks and Machine Learning - ICANN 2018. Pt Iii, 11141, 270–279

    Google Scholar 

  25. Mabu, S., Atsumo, A., Kido, S., Kuremoto, T., & Hirano, Y. (2020). Investigating the effects of transfer learning on ROI-based classification of chest CT scan images: A case study on diffuse lung diseases. Journal of Signal Processing Systems, 92(3), 307–313

    Article  Google Scholar 

  26. Sharif Razavian, A., Azizpour, H., Sullivan, J., & Carlsson, S. (2014). CNN features off-the-shelf: an astounding baseline for recognition. Proceedings of the IEEE Conference on Computer Vision and Pattern Recognition Workshops, 806–813

  27. Donahue, J., Jia, Y., Vinyals, O., Hoffman, J., Zhang, N., Tzeng, E., & Darrell, T. (2014). DeCAF: A deep convolutional activation feature for generic visual recognition. Proc. International Conference on Machine Learning, 647–655

  28. Hur, C., & Kang, S. (2020). On-device partial learning technique of convolutional neural network for new classes. Journal of Signal Processing Systems. https://doi.org/10.1007/s11265-020-01520-7

    Article  Google Scholar 

  29. Yosinski, J., Clune, J., Bengio, Y., & Lipson, H. (2014). How transferable are features in deep neural networks?. Proc. Advances in Neural Information Processing Systems, 3320–3328

  30. Bayramoglu, N., & Heikkilä, J. (2014). Transfer learning for cell nuclei classification in histopathology images. Proc. European Conference on Computer Vision, 532–539

  31. Li, Z. Z., & Hoiem, D. (2018). Learning without forgetting. IEEE Transactions on Pattern Analysis and Machine Intelligence, 40(12), 2935–2947

    Article  Google Scholar 

  32. Shia, W. C., & Chen, D. R. (2021). Classification of malignant tumors in breast ultrasound using a pretrained deep residual network model and support vector machine. Computerized Medical Imaging and Graphics, 87, 101829

  33. Hira, Z. M., & Gillies, D. F. (2015). A review of feature selection and feature extraction methods applied on microarray data. Advances in Bioinformatics, 198363

  34. Guo, Y., Shi, H., Kumar, A., Grauman, K., Rosing, T., & Feris, R. (2018). SpotTune: transfer learning through adaptive fine-tuning. Proceedings of the IEEE Conference on Computer Vision and Pattern Recognition, 4805–4814

  35. Ali, M., Son, D. H., Kang, S. H., & Nam, S. R. (2017). An accurate CT saturation classification using a deep learning approach based on unsupervised feature extraction and supervised fine-tuning strategy. Energies, 10(11), 1830

    Article  Google Scholar 

  36. Boyd, A., Czajka, A., & Bowyer, K. (2019). Deep learning-based feature extraction in iris recognition: Use existing models, fine-tune or train from scratch? Proc. 2019 IEEE 10th International Conference on Biometrics Theory, Applications and Systems (BTAS), IEEE, 1–9

  37. Bai, Y., Yi, J. Y., Tao, J. H., Wen, Z. Q., & Fan, C. H. (2020). A public Chinese dataset for language model adaptation. Journal of Signal Processing Systems, 92(8), 839–851

    Article  Google Scholar 

  38. Reyes, A. K., Caicedo, J. C., & Camargo, J. E. (2015). Fine-tuning deep convolutional networks for plant recognition. CLEF (Working Notes), 1391, 467–475

    Google Scholar 

  39. Zhou, Z., Shin, J., Zhang, L., Gurudu, S., Gotway, M., & Liang, J. (2017). Fine-tuning convolutional neural networks for biomedical image analysis: actively and incrementally. Proceedings of the IEEE Conference on Computer Vision And Pattern Recognition, 7340–7351

  40. Kensert, A., Harrison, P. J., & Spjuth, O. (2019). Transfer learning with deep convolutional neural networks for classifying cellular morphological changes. SLAS DISCOVERY: Advancing Life Sciences R&D, 24(4), 466–475

    Article  Google Scholar 

  41. Sun, C., Qiu, X., Xu, Y., & Huang, X. (2019). How to fine-tune BERT for text classification? Proc. China National Conference on Chinese Computational Linguistics, Springer, 194–206

  42. Swati, Z. N. K., Zhao, Q., Kabir, M., Ali, F., Ali, Z., Ahmed, S., & Lu, J. (2019). Brain tumor classification for MR images using transfer learning and fine-tuning. Computerized Medical Imaging and Graphics, 75, 34–46

    Article  Google Scholar 

  43. Nazir, M., Shakil, S., & Khurshid, K. (2021). Role of deep learning in brain tumor detection and classification (2015 to 2020): A review. Computerized Medical Imaging and Graphics, 101940

  44. Srivastava, N., Hinton, G., Krizhevsky, A., Sutskever, I., & Salakhutdinov, R. (2014). Dropout: A simple way to prevent neural networks from overfitting. Journal of Machine Learning Research, 15, 1929–1958

    MathSciNet  MATH  Google Scholar 

  45. Goodfellow, I., Bengio, Y., & Courville, A. (2016). Deep Learning, MIT press Cambridge

  46. Adelabu, S., Mutanga, O., & Adam, E. (2015). Testing the reliability and stability of the internal accuracy assessment of random forest for classifying tree defoliation levels using different validation methods. Geocarto International, 30(7), 810–821

    Article  Google Scholar 

  47. Xu, Y., & Goodacre, R. (2018). On splitting training and validation set: A comparative study of cross-validation, bootstrap and systematic sampling for estimating the generalization performance of supervised learning. Journal of Analysis and Testing, 2(3), 249–262

    Article  Google Scholar 

  48. Hsu, C. W., & Lin, C. J. (2002). A comparison of methods for multiclass support vector machines. IEEE Transactions on Neural Networks, 13(2), 415–425

    Article  Google Scholar 

  49. Szegedy, C., Vanhoucke, V., Ioffe, S., Shlens, J., & Wojna, Z. (2016) IEEE Rethinking the Inception Architecture for Computer Vision. Proceddings of the IEEE Conference on Computer Vision and Pattern Recognition, 2818–2826

  50. Dong, N., Zhao, L., Wu, C. H., & Chang, J. F. (2020). Inception v3 based cervical cell classification combined with artificially extracted features. Applied Soft Computing, 93, 106311

  51. Xia, X. L., Xu, C., & Nan, B. (2017). IEEE Inception-v3 for Flower Classification. 2nd International Conference on Image, Vision and Computing, 783–787

  52. Tian, X., & Chen, C. (2019). IEEE Modulation Pattern Recognition Based on Resnet50 Neural Network. 2nd IEEE International Conference on Information Communication and Signal Processing, 34–38

  53. Wang, C., Chen, D. L., Hao, L., Liu, X. B., Zeng, Y., Chen, J. W., & Zhang, G. K. (2019). Pulmonary image classification based on inception-v3 transfer learning model. IEEE Access, 7, 146533–146541

    Article  Google Scholar 

Download references

Acknowledgement

The research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number 1R21GM134544. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Author information

Authors and Affiliations

Authors

Contributions

Aminul Islam Khan: Methodology, Investigation, Data Processing, Writing and Analysis. Min Jun Kim: Writing and Funding Acquisition. Prashanta Dutta: Methodology, Writing and Analysis, Supervision, and Funding Acquisition.

Corresponding author

Correspondence to Prashanta Dutta.

Ethics declarations

Ethics Approval

Not applicable.

Consent to Participate

Yes.

Consent for Publication

Yes.

Conflicts of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 636 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Khan, A.I., Kim, M.J. & Dutta, P. Fine-tuning-based Transfer Learning for Characterization of Adeno-Associated Virus. J Sign Process Syst 94, 1515–1529 (2022). https://doi.org/10.1007/s11265-022-01758-3

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11265-022-01758-3

Keywords

Navigation