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A Link-Based Ensemble Cluster Approach for Identification of Cell Types

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Intelligent Computing Theories and Application (ICIC 2021)

Part of the book series: Lecture Notes in Computer Science ((LNISA,volume 12837))

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Abstract

Clustering is a necessary step in analyzing single-cell RNA-seq (sRNA-seq) data to illuminate the complexity of the tissue, including the number of cell types and transcriptome characteristics of each cell type. However, the clustering results obtained from different single-cell clustering methods are often different, and sometimes even contradictory conclusions are drawn. Biologists often cannot obtain the correct clustering results. To overcome this challenge, researchers have developed an integrated learning strategy that can effectively solve this problem. Here, we propose a new unsupervised ensemble clustering method LE2CT. First, we obtained five clustering results that have been used in the scRNA-seq data clustering method. Second, we construct a similarity consensus matrix based on multiple clustering solutions. Finally, hierarchical clustering is used as a consensus function to generate final data partitions. We identified cell clusters on twelve scRNA-seq benchmark data sets and used the adjusted RAND index (ARI) and normalized mutual information (NMI) to measure the accuracy of clustering. The experimental results are encouraging. Compared with the classic single clustering method, LE2CT has higher clustering accuracy and stronger robustness in various data sets, which shows that LE2CT has a competitive advantage compared with existing methods.

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References

  1. Toyooka, Y., Shimosato, D., Murakami, K., Takahashi, K., Niwa, H.: Identification and characterization of subpopulations in undifferentiated ES cell culture. Development 135, 909–918 (2008)

    Article  Google Scholar 

  2. Bumgarner, S.L., et al.: Single-cell analysis reveals that noncoding RNAs contribute to clonal heterogeneity by modulating transcription factor recruitment. Mol. Cell 45, 470–482 (2012)

    Article  Google Scholar 

  3. Chang, H.H., Hemberg, M., Barahona, M., Ingber, D.E., Huang, S.: Transcriptome-wide noise controls lineage choice in mammalian progenitor cells. Nature 453, 544–547 (2008)

    Article  Google Scholar 

  4. Shalek, A.K., et al.: Single-cell RNA-seq reveals dynamic paracrine control of cellular variation. Nature 510, 363–369 (2014)

    Article  Google Scholar 

  5. Zhang, T.Q., Xu, Z.G., Shang, G.D., Wang, J.W.: A single-cell RNA sequencing profiles the developmental landscape of arabidopsis root. Mol. Plant 12, 648–660 (2019)

    Article  Google Scholar 

  6. Nguyen, Q.H., et al.: cRNA-seq of human induced pluripotent stem cells reveals cellular heterogeneity and cell state transitions between subpopulations. Genome Res. 28, 1053–1066 (2018)

    Article  Google Scholar 

  7. Zhao, Q., et al.: Single-cell transcriptome analyses reveal endothelial cell heterogeneity in tumors and changes following antiangiogenic treatment. Cancer Res. 78, 2370–2382 (2018)

    Article  Google Scholar 

  8. Calbo, J., et al.: A functional role for tumor cell heterogeneity in a mouse model of small cell lung cancer. Cancer Cell 19, 244–256 (2011)

    Article  Google Scholar 

  9. Tellez-Gabriel, M., Ory, B., Lamoureux, F., Heymann, M.F., Heymann, D.: Tumour heterogeneity: the key advantages of single-cell analysis. Int. J. Mol. Sci. 17, 2142 (2016)

    Article  Google Scholar 

  10. Walzer, K.A., Fradin, H., Emerson, L.Y., Corcoran, D.L., Chi, J.T.: Latent transcriptional variations of individual Plasmodium falciparum uncovered by single-cell RNA-seq and fluorescence imaging. PLoS Genet. 15, e1008506 (2019)

    Article  Google Scholar 

  11. Wen, L., Tang, F.: Single-cell sequencing in stem cell biology. Genome Biol. 17, 71 (2016)

    Article  Google Scholar 

  12. Dagogo-Jack, I., Shaw, A.T.: Tumour heterogeneity and resistance to cancer therapies. Nat. Rev. Clin. Oncol. 15, 81–94 (2018)

    Article  Google Scholar 

  13. Saliba, A.-E., Westermann, A.J., Gorski, S.A., Vogel, J.: Single-cell RNA-seq: advances and future challenges. Nucleic Acids Res. 42(14), 8845–8860 (2014)

    Article  Google Scholar 

  14. Haque, A., Engel, J., Teichmann, S.A., Lönnberg, T.: A practical guide to single-cell RNA-sequencing for biomedical research and clinical applications. Genome Med. 9(1), 75 (2017)

    Article  Google Scholar 

  15. Chung, W., et al.: Single-cell RNA-seq enables comprehensive tumour and immune cell profiling in primary breast cancer. Nat. Commun. 8, 15081 (2017)

    Article  Google Scholar 

  16. Li, W.V., Li, J.J.: An accurate and robust imputation method scimpute for single-cell rna-seq data. Nat. Commun. 9(1), 997 (2018)

    Article  Google Scholar 

  17. Stegle, O., Teichmann, S.A., Marioni, J.C.: Computational and analytical challenges in single-cell transcriptomics. Nat. Rev. Genet. 16(3), 133 (2015)

    Article  Google Scholar 

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

    Article  Google Scholar 

  19. Andrews, T.S., Hemberg, M.: M3Drop: dropout-based feature selection for scRNASeq. Bioinformatics 35, 2865–2867 (2019)

    Article  Google Scholar 

  20. Grun, D.: Revealing dynamics of gene expression variability in cell state space. Nat. Methods 17, 45–49 (2020)

    Article  Google Scholar 

  21. Yau, C., et al.: pcareduce: hierarchical clustering of single cell transcriptional profiles. BMC Bioinforma 17(1), 140 (2016). https://doi.org/10.1186/s12859-016-0984-y

    Article  MathSciNet  Google Scholar 

  22. Xu, C., Su, Z.: Identification of cell types from single-cell transcriptomes using a novel clustering method. Bioinformatics 31(12), 1974–1980 (2015)

    Article  Google Scholar 

  23. Kiselev, V.Y., et al.: Sc3: consensus clustering of single-cell rna-seq data. Nat. Methods 14(5), 483 (2017)

    Article  MathSciNet  Google Scholar 

  24. Biase, F.H., Cao, X., Zhong, S.: Cell fate inclination within 2-cell and 4-cell mouse embryos revealed by single-cell RNA sequencing. Genome Res. 24, 1787–1796 (2014)

    Article  Google Scholar 

  25. Zheng, G., Terry, J.M., Belgrader, P., Ryvkin, P., Bent, Z.W., Wilson, R., et al.: Massively parallel digital transcriptional profiling of single cells. Nat. Commun. 8, 14049 (2017)

    Article  Google Scholar 

  26. Yang, M., Guo, H., Yang, L., Wu, J., Li, R., et al.: Single-cell RNA-seq profiling of human preimplantation embryos and embryonic stem cells. Nat. Struct. Mol. Biol. 20, 1131–1139 (2013)

    Article  Google Scholar 

  27. Goolam, M., Scialdone, A., Graham, S.J., Macaulay, I.C., Jedrusik, A., Hupalowska, A., et al.: Heterogeneity in Oct4 and Sox2 targets biases cell fate in 4-cell mouse embryos. Cell 165, 61–74 (2016)

    Article  Google Scholar 

  28. Darmanis, S., Sloan, S.A., Zhang, Y., Enge, M., Caneda, C., Shuer, L.M., et al.: A survey of human brain transcriptome diversity at the single cell level. Proc. Natl. Acad. Sci. U.S.A. 112, 7285–7290 (2015)

    Article  Google Scholar 

  29. Xin, Y., et al.: RNA sequencing of single human Islet cells reveals type 2 diabetes genes. Cell Metab. 24, 608–615 (2016)

    Article  Google Scholar 

  30. Pollen, A.A., Nowakowski, T.J., Shuga, J., et al.: Low-coverage single-cell mRNA sequencing reveals cellular heterogeneity and activated signaling pathways in developing cerebral cortex. Nat. Biotechnol. 32(10), 1053–1058 (2014)

    Article  Google Scholar 

  31. Kolodziejczyk, A.A., et al.: Single cell RNA-sequencing of pluripotent states unlocks modular transcriptional variation. Cell Stem Cell 17, 471–485 (2015)

    Article  Google Scholar 

  32. Usoskin, D., et al.: Unbiased classification of sensory neuron types by large-scale single-cell RNA sequencing. Nat. Neurosci. 18, 145–153 (2015)

    Article  Google Scholar 

  33. Tasic, B., et al.: Adult mouse cortical cell taxonomy revealed by single cell transcriptomics. Nat. Neurosci. 19, 335–346 (2016)

    Article  Google Scholar 

  34. Muraro, M.J., et al.: A single-cell transcriptome atlas of the human pancreas. Cell Syst. 3, 385-394.e3 (2016)

    Article  Google Scholar 

  35. Zeisel, A., et al.: Brain structure. Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq. Science 347, 1138–1142 (2015)

    Google Scholar 

  36. Macosko, E.Z., et al.: Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets. Cell 161(5), 1202–1214 (2015)

    Article  Google Scholar 

  37. Wang, B., Zhu, J., Pierson, E., Ramazzotti, D., Batzoglou, S.: Visualization and analysis of single-cell RNA-seq data by kernel-based similarity learning. Nat. Methods 14(4), 414–416 (2017)

    Article  Google Scholar 

  38. Lin, P., Troup, M., Ho, J.W.K.: CIDR: ultrafast and accurate clustering through imputation for single-cell RNA-seq data. Genome Biol. 18(1), 59 (2017)

    Article  Google Scholar 

  39. Grün, D., Lyubimova, A., Kester, L., Wiebrands, K., Basak, O., Sasaki, N., et al.: Single-cell messenger RNA sequencing reveals rare intestinal cell types. Nature 525(7568), 251–255 (2015)

    Article  Google Scholar 

  40. Jeh, G., Widom, J.: SimRank: a measure of structural-context similarity. In: The Eighth ACM SIGKDD International Conference ACM, pp. 538–543 (2002)

    Google Scholar 

Download references

Acknowledgements

This work was supported by Natural Science Foundation of China (Grant No. 61972141) and Natural Science Foundation of Hunan Province, China (Grant No. 2018JJ2053).

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Lu, X., Gao, Y., Tang, D., Yuan, Y. (2021). A Link-Based Ensemble Cluster Approach for Identification of Cell Types. In: Huang, DS., Jo, KH., Li, J., Gribova, V., Hussain, A. (eds) Intelligent Computing Theories and Application. ICIC 2021. Lecture Notes in Computer Science(), vol 12837. Springer, Cham. https://doi.org/10.1007/978-3-030-84529-2_54

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  • DOI: https://doi.org/10.1007/978-3-030-84529-2_54

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  • Online ISBN: 978-3-030-84529-2

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