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ScDA: A Denoising AutoEncoder Based Dimensionality Reduction for Single-cell RNA-seq Data

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Bioinformatics Research and Applications (ISBRA 2021)

Part of the book series: Lecture Notes in Computer Science ((LNBI,volume 13064))

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Abstract

Single-cell RNA-seq (scRNA-seq) data has provided a higher resolution of cellular heterogeneity. However, scRNA-seq data also brings some computational challenges for its high-dimension, high-noise, and high-sparseness. The dimension reduction is a crucial way to denoise and greatly reduce the computational complexity by representing the original data in a low-dimensional space. In this study, to achieve an accurate low-dimension representation, we proposed a denoising AutoEncoder based dimensionality reduction method for scRNA-seq data (ScDA), combining the denoising function with the AutoEncoder. ScDA is a deep unsupervised generative model, which models the dropout events and denoises the scRNA-seq data. Meanwhile, ScDA can reveal the nonlinear feature extraction of the original data through maximum distribution similarity before and after dimensionality reduction. Tested on 16 scRNA-seq datasets, ScDA provides superior average performances, and especially superior performances in large-scale datasets compared with 3 clustering methods.

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Authors’ Contributions

Conceptualization, X.Z., X.P., and J.W.; Methodology, X.Z., Y.L., and X.P.; Software, Y.L., and J.L.; Writing-Original Draft Preparation, X.Z., J.W., and X.P.; Visualization, Y.L.; Funding Acquisition, X.Z., and X.P.

References

  1. Vitak, S.A., et al.: Sequencing thousands of single-cell genomes with combinatorial indexing. Nat. Methods 14(3), 302 (2017)

    Article  CAS  Google Scholar 

  2. Stuart, T., Satija, R.: Integrative single-cell analysis. Nat. Rev. Genet. 20(5), 257–272 (2019)

    Article  CAS  Google Scholar 

  3. Laehnemann, D., Kster, J., Szczurek, E., Mccarthy, D.J., Schnhuth, A.: Eleven grand challenges in single-cell data science. Genome Biol. 21(1), 31 (2020)

    Article  Google Scholar 

  4. Wolf, F.A., et al.: PAGA: graph abstraction reconciles clustering with trajectory inference through a topology preserving map of single cells. Genome Biol. 20(1), 59 (2019)

    Article  Google Scholar 

  5. Taiyun, K., Chen, I.R., Lin, Y., Wang, Y.Y., Yang, J., Yang, P.: Impact of similarity metrics on single-cell RNA-seq data clustering. Brief. Bioinform. 20(6), 2316–2326 (2018)

    Google Scholar 

  6. Eling, N., Morgan, M.D., Marioni, J.C.: Challenges in measuring and understanding biological noise. Nat. Rev. Genet. 20(9), 536–548 (2019)

    Article  CAS  Google Scholar 

  7. Andrews, T.S., Hemberg, M., Birol, I.: Dropout-based feature selection for scRNASeq. Bioinformatics 35(16), 2865–2867 (2018)

    Article  Google Scholar 

  8. Wang, D.: VASC: Dimension reduction and visualization of single-cell RNA-seq data by deep variational autoencoder. Genomics Proteomics Bioinformatics 16(5), 320–331 (2018)

    Article  Google Scholar 

  9. Raphael, P., Li, Z., Kuang, R.: Machine learning and statistical methods for clustering single-cell RNA-sequencing data. Brief. Bioinform. 4, 4 (2019)

    Google Scholar 

  10. Kiselev, V.Y., et al.: SC3: consensus clustering of single-cell RNA-seq data. Nat. Methods 14(5), 483 (2017)

    Article  CAS  Google Scholar 

  11. Jia, C., Hu, Y., Derek, K., Junhyong, K., Li, M., Zhang, N.R.: Accounting for technical noise in differential expression analysis of single-cell RNA sequencing data. Nucleic Acids Res. 19, 10978 (2017)

    Article  Google Scholar 

  12. Liu, Z., et al.: Reconstructing cell cycle pseudo time-series via single-cell transcriptome data. Nat. Commun. 8(1), 22 (2017)

    Article  Google Scholar 

  13. Saelens, W., Cannoodt, R., Todorov, H., Saeys, Y.: A comparison of single-cell trajectory inference methods. Nat. Biotechnol. 37(5), 547–554 (2019)

    Article  CAS  Google Scholar 

  14. Llorens-Bobadilla, E., Zhao, S., Baser, A., Saiz-Castro, G., Zwadlo, K., Martin-Villalba, A.: Single-cell transcriptomics reveals a population of dormant neural stem cells that become activated upon brain injury. Cell Stem Cell 17(3), 329–340 (2015)

    Article  CAS  Google Scholar 

  15. Spyros, D., et al.: Hayden, Barres BA, Quake SR: A survey of human brain transcriptome diversity at the single cell level. Proc. Natl. Acad. Sci. 112(23), 7285–7290 (2015)

    Article  Google Scholar 

  16. GiniClust3: a fast and memory-efficient tool for rare cell type identification. BMC Bioinformatics 21(1), 158 (2020)

    Google Scholar 

  17. Zhu, X., Zhang, J., Xu, Y., Wang, J., Peng, X., Li, H.-D.: Single-cell clustering based on shared nearest neighbor and graph partitioning. Interdisc. Sci.: Computat. Life Sci. (2020)

    Google Scholar 

  18. Yip, S.H., Chung, S.P., Wang, J.: Evaluation of tools for highly variable gene discovery from single-cell RNA-seq data. Brief. Bioinform. 4, 4 (2018)

    Google Scholar 

  19. Becht, E., et al.: Dimensionality reduction for visualizing single-cell data using UMAP. Nat. Biotechnol. 37, 38–44 (2019)

    Article  CAS  Google Scholar 

  20. Tian, T., Wan, J., Song, Q., Wei, Z.: Clustering single-cell RNA-seq data with a model-based deep learning approach. Nat. Mach. Intell. 1(4), 191–198 (2019)

    Article  Google Scholar 

  21. Wan, S., Kim, J., Won, K.J.: SHARP: hyper-fast and accurate processing of single-cell RNA-seq data via ensemble random projection. Genome Res. 30(2), gr.254557.254119 (2020)

    Google Scholar 

  22. Liang, Z., Li, M., Zheng, R., Tian, Y., Wang, J.: SSRE: cell type detection based on sparse subspace representation and similarity enhancement. Genomics Proteomics Bioinformatics S1762–0229(21), 00038–33 (2020)

    Google Scholar 

  23. Song, J., Liu, Y., Zhang, X., Wu, Q., Yang, C.: Entropy subspace separation-based clustering for noise reduction (ENCORE) of scRNA-seq data. Nucleic Acids Res. 49(3), e18 (2020)`

    Google Scholar 

  24. Kiselev, V.Y., Andrews, T.S., Hemberg, M.: Challenges in unsupervised clustering of single-cell RNA-seq data. Nat. Rev. Genet. 20(5), 273–282 (2019)

    Article  CAS  Google Scholar 

  25. Soneson, C., Robinson, M.D.: Bias, robustness and scalability in single-cell differential expression analysis. Nat. Methods 15(4), 255–261 (2018)

    Article  CAS  Google Scholar 

  26. Estevez, P.A., Tesmer, M., Perez, C.A., Zurada, J.M.: Normalized mutual information feature selection. IEEE Trans. Neural Netw. 20(2), 189–201 (2009)

    Article  Google Scholar 

  27. Hubert, L., Arabie, P.: Comparing partitions. J. Classif. 2(1), 193–218 (1985)

    Google Scholar 

  28. Heterogeneity in Oct4 and Sox2 targets biases cell fate in 4-cell mouse embryos. Cell 165(1), 61–74 (2016)

    Google Scholar 

  29. Kumar, R.M., et al.: Deconstructing transcriptional heterogeneity in pluripotent stem cells. Nature 16(7529), 56–61 (2014)

    Article  Google Scholar 

  30. Wang, Y.J., et al.: Single-cell transcriptomics of the human endocrine pancreas. Diabetes 65(10), 3028 (2016)

    Article  CAS  Google Scholar 

  31. Wallrapp, A., et al.: The neuropeptide NMU amplifies ILC2-driven allergic lung inflammation. Nature 549(7672), 351–356 (2017)

    Article  CAS  Google Scholar 

  32. Patel, A.P., et al.: Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science 344(6190), 1396–1401 (2014)

    Article  CAS  Google Scholar 

  33. Haber, A.L., et al.: A single-cell survey of the small intestinal epithelium. Nature 551(7680), 333–339 (2017)

    Article  CAS  Google Scholar 

  34. Petropoulos, S., et al.: Single-cell RNA-Seq reveals lineage and x chromosome dynamics in human preimplantation embryos. Cell 165(4), 1012–1026 (2016)

    Article  CAS  Google Scholar 

  35. Klein, A., et al.: Droplet barcoding for single-cell transcriptomics applied to embryonic stem cells. Cell 161(5), 1187–1201 (2015)

    Article  CAS  Google Scholar 

  36. Han, X., Wang, R., Zhou, Y., Fei, L., Guo, G.: Mapping the mouse cell atlas by Microwell-Seq. Cell 172(5), 1091-1107.e1017 (2018)

    Article  CAS  Google Scholar 

  37. Grün, D., et al.: De novo prediction of stem cell identity using single-cell transcriptome data. Cell Stem Cell 19(2), 266–277 (2016)

    Article  Google Scholar 

  38. Cao, J., et al.: Comprehensive single-cell transcriptional profiling of a multicellular organism. Science 357(6352), 661 (2017)

    Article  CAS  Google Scholar 

  39. Spallanzani, R.G., Zemmour, D., Xiao, T., Jayewickreme, T., Mathis, D.: Distinct immunocyte-promoting and adipocyte-generating stromal components coordinate adipose tissue immune and metabolic tenors. Sci. Immunol. 4(35), eaaw3658 (2019)

    Google Scholar 

  40. Zemmour, D., Zilionis, R., Kiner, E., Klein, A.M., Mathis, D., Benoist, C.: Single-cell gene expression reveals a landscape of regulatory T cell phenotypes shaped by the TCR. Nat. Immunol. 19(3), 291–301 (2018)

    Article  CAS  Google Scholar 

  41. Frigerio, C.S., et al.: The major risk factors for Alzheimer’s disease: age, sex, and genes modulate the microglia response to Aβ plaques. Cell Rep. 27(4), 1293-1306.e1296 (2019)

    Article  Google Scholar 

  42. Shekhar, K., et al.: Comprehensive classification of retinal bipolar neurons by single-cell transcriptomics. Cell 166(5), 1308-1323.e1330 (2016)

    Article  CAS  Google Scholar 

Download references

Funding

This research was supported by the National Natural Science Foundation of China (No. 61762087, 61702555, 61772557), Hunan Provincial Science and Technology Program (2018WK4001), 111 Project (No. B18059), Guangxi Natural Science Foundation (No. 2018JJA170175).

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Correspondence to Xiaoqing Peng .

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Zhu, X., Lin, Y., Li, J., Wang, J., Peng, X. (2021). ScDA: A Denoising AutoEncoder Based Dimensionality Reduction for Single-cell RNA-seq Data. In: Wei, Y., Li, M., Skums, P., Cai, Z. (eds) Bioinformatics Research and Applications. ISBRA 2021. Lecture Notes in Computer Science(), vol 13064. Springer, Cham. https://doi.org/10.1007/978-3-030-91415-8_45

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  • DOI: https://doi.org/10.1007/978-3-030-91415-8_45

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