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Reseach Article

Effects of Pseudotime Uncertainty in Downstream Analysis for Single-cell Data: A Case Study

by Sumon Ahmed
International Journal of Computer Applications
Foundation of Computer Science (FCS), NY, USA
Volume 175 - Number 18
Year of Publication: 2020
Authors: Sumon Ahmed
10.5120/ijca2020920696

Sumon Ahmed . Effects of Pseudotime Uncertainty in Downstream Analysis for Single-cell Data: A Case Study. International Journal of Computer Applications. 175, 18 ( Sep 2020), 1-6. DOI=10.5120/ijca2020920696

@article{ 10.5120/ijca2020920696,
author = { Sumon Ahmed },
title = { Effects of Pseudotime Uncertainty in Downstream Analysis for Single-cell Data: A Case Study },
journal = { International Journal of Computer Applications },
issue_date = { Sep 2020 },
volume = { 175 },
number = { 18 },
month = { Sep },
year = { 2020 },
issn = { 0975-8887 },
pages = { 1-6 },
numpages = {9},
url = { https://ijcaonline.org/archives/volume175/number18/31549-2020920696/ },
doi = { 10.5120/ijca2020920696 },
publisher = {Foundation of Computer Science (FCS), NY, USA},
address = {New York, USA}
}
%0 Journal Article
%1 2024-02-07T00:25:20.904549+05:30
%A Sumon Ahmed
%T Effects of Pseudotime Uncertainty in Downstream Analysis for Single-cell Data: A Case Study
%J International Journal of Computer Applications
%@ 0975-8887
%V 175
%N 18
%P 1-6
%D 2020
%I Foundation of Computer Science (FCS), NY, USA
Abstract

The analysis of high-throughput single-cell genomics data creates opportunities to uncover the temporal dynamics of cell populations undergoing some complex biological processes such as differentiation and cell division, where the development of bulk-based time course experiments is challenging or technically impossible. One popular approach is to learn a lower-dimensional manifold or trajectory called pseudotime through the data capturing major sources of variation. Most of the current approaches of trajectory inference only provide a point estimate of pseudotime, concealing the consequence of inherent biological and technical noise in single-cell data. Therefore, the intrinsic uncertainty in pseudotime and trajectory inference is not propagated to the downstream and its effects remain unknown. Here three commonly used pseudotime and trajectory inference methods have been discussed along with an important downstream analysis of trajectory inference, i.e. identification of gene-specific branching locations. The alteration of gene-specific branching locations in downstream is illustrated for different pseudotime and trajectory inference methods used in upstream. Finally, A set of recommendations is made that the downstream results or hypotheses should be confirmed using several pseudotime and trajectory inference methods.

References
  1. Fuchou Tang, Catalin Barbacioru, Yangzhou Wang, Ellen Nordman, Clarence Lee, Nanlan Xu, Xiaohui Wang, John Bodeau, Brian B Tuch, Asim Siddiqui, et al. mrna-seq whole-transcriptome analysis of a single cell. Nature methods, 6(5):377, 2009.
  2. Evan Z Macosko, Anindita Basu, Rahul Satija, James Nemesh, Karthik Shekhar, Melissa Goldman, Itay Tirosh, Allison R Bialas, Nolan Kamitaki, Emily M Martersteck, et al. Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets. Cell, 161(5):1202–1214, 2015.
  3. Grace XY Zheng, Jessica M Terry, Phillip Belgrader, Paul Ryvkin, Zachary W Bent, Ryan Wilson, Solongo B Ziraldo, Tobias D Wheeler, Geoff P McDermott, Junjie Zhu, et al. Massively parallel digital transcriptional profiling of single cells. Nature communications, 8:14049, 2017.
  4. Charles Gawad, Winston Koh, and Stephen R Quake. Single-cell genome sequencing: current state of the science. Nature Reviews Genetics, 17(3):175, 2016.
  5. Byungjin Hwang, Ji Hyun Lee, and Duhee Bang. Single-cell rna sequencing technologies and bioinformatics pipelines. Experimental & molecular medicine, 50(8):1–14, 2018.
  6. Dominic Gr¨un, Anna Lyubimova, Lennart Kester, Kay Wiebrands, Onur Basak, Nobuo Sasaki, Hans Clevers, and Alexander van Oudenaarden. Single-cell messenger rna sequencing reveals rare intestinal cell types. Nature, 525(7568):251, 2015.
  7. Aleksandra A Kolodziejczyk, Jong Kyoung Kim, Valentine Svensson, John C Marioni, and Sarah A Teichmann. The technology and biology of single-cell rna sequencing. Molecular cell, 58(4):610–620, 2015.
  8. Cole Trapnell, Davide Cacchiarelli, Jonna Grimsby, Prapti Pokharel, Shuqiang Li, Michael Morse, Niall J Lennon, Kenneth J Livak, Tarjei S Mikkelsen, and John L Rinn. The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells. Nature biotechnology, 32(4):381–386, 2014.
  9. Barbara Treutlein, Doug G Brownfield, Angela R Wu, Norma F Neff, Gary L Mantalas, F Hernan Espinoza, Tushar J Desai, Mark A Krasnow, and Stephen R Quake. Reconstructing lineage hierarchies of the distal lung epithelium using single-cell rna-seq. Nature, 509(7500):371, 2014.
  10. Franziska Paul, Yaara Arkin, Amir Giladi, Diego Adhemar Jaitin, Ephraim Kenigsberg, Hadas Keren-Shaul, Deborah Winter, David Lara-Astiaso, Meital Gury, AssafWeiner, et al. Transcriptional heterogeneity and lineage commitment in myeloid progenitors. Cell, 163(7):1663–1677, 2015.
  11. Monika S Kowalczyk, Itay Tirosh, Dirk Heckl, Tata Nageswara Rao, Atray Dixit, Brian J Haas, Rebekka K Schneider, Amy J Wagers, Benjamin L Ebert, and Aviv Regev. Single-cell rna-seq reveals changes in cell cycle and differentiation programs upon aging of hematopoietic stem cells. Genome research, 25(12):1860–1872, 2015.
  12. Fan Zhou, Xianlong Li, Weili Wang, Ping Zhu, Jie Zhou, Wenyan He, Meng Ding, Fuyin Xiong, Xiaona Zheng, Zhuan Li, et al. Tracing haematopoietic stem cell formation at single-cell resolution. Nature, 533(7604):487, 2016.
  13. Tapio L¨onnberg, Valentine Svensson, Kylie R James, Daniel Fernandez-Ruiz, Ismail Sebina, Ruddy Montandon, Megan SF Soon, Lily G Fogg, Arya Sheela Nair, Urijah Liligeto, et al. Single-cell rna-seq and computational analysis using temporal mixture modelling resolves th1/tfh fate bifurcation in malaria. Science immunology, 2(9), 2017.
  14. Michael JT Stubbington, Tapio L¨onnberg, Valentina Proserpio, Simon Clare, Anneliese O Speak, Gordon Dougan, and Sarah A Teichmann. T cell fate and clonality inference from single-cell transcriptomes. Nature methods, 13(4):329, 2016.
  15. Junyue Cao, Malte Spielmann, Xiaojie Qiu, Xingfan Huang, Daniel M Ibrahim, Andrew J Hill, Fan Zhang, Stefan Mundlos, Lena Christiansen, Frank J Steemers, et al. The single-cell transcriptional landscape of mammalian organogenesis. Nature, 566(7745):496, 2019.
  16. Guoji Guo, Mikael Huss, Guo Qing Tong, Chaoyang Wang, Li Li Sun, Neil D Clarke, and Paul Robson. Resolution of cell fate decisions revealed by single-cell gene expression analysis from zygote to blastocyst. Developmental cell, 18(4):675–685, 2010.
  17. Zhicheng Ji and Hongkai Ji. TSCAN: Pseudo-time reconstruction and evaluation in single-cell rna-seq analysis. Nucleic acids research, 44(13), 2016.
  18. Tsukasa Kouno, Michiel de Hoon, Jessica C Mar, Yasuhiro Tomaru, Mitsuoki Kawano, Piero Carninci, Harukazu Suzuki, Yoshihide Hayashizaki, and Jay W Shin. Temporal dynamics and transcriptional control using single-cell gene expression analysis. Genome biology, 14(10):R118, 2013.
  19. Neil Lawrence. Probabilistic non-linear principal component analysis with gaussian process latent variable models. Journal of Machine Learning Research, 6(Nov):1783–1816, 2005.
  20. John E Reid and Lorenz Wernisch. Pseudotime estimation: deconfounding single cell time series. Bioinformatics, 32(19):2973–2980, 2016.
  21. Florian Buettner and Fabian J Theis. A novel approach for resolving differences in single-cell gene expression patterns from zygote to blastocyst. Bioinformatics, 28(18):i626–i632, 2012.
  22. Kieran Campbell and Christopher Yau. Order under uncertainty: robust differential expression analysis using probabilistic models for pseudotime inference. PLoS Computational Biology, 12(11), 2016.
  23. Sumon Ahmed, Magnus Rattray, and Alexis Boukouvalas. Grandprix: scaling up the bayesian gplvm for single-cell data. Bioinformatics, 35(1):47–54, 2019.
  24. John T Dimos, Kit T Rodolfa, Kathy K Niakan, Laurin M Weisenthal, Hiroshi Mitsumoto, Wendy Chung, Gist F Croft, Genevieve Saphier, Rudy Leibel, Robin Goland, et al. Induced pluripotent stem cells generated from patients with als can be differentiated into motor neurons. science, 321(5893):1218–1221, 2008.
  25. Ryohichi Sugimura, Deepak Kumar Jha, Areum Han, Clara Soria-Valles, Edroaldo Lummertz Da Rocha, Yi-Fen Lu, Jeremy A Goettel, Erik Serrao, R Grant Rowe, Mohan Malleshaiah, et al. Haematopoietic stem and progenitor cells from human pluripotent stem cells. Nature, 545(7655):432, 2017.
  26. Raphael Lis, Charles C Karrasch, Michael G Poulos, Balvir Kunar, David Redmond, Jose G Barcia Duran, Chaitanya R Badwe, William Schachterle, Michael Ginsberg, Jenny Xiang, et al. Conversion of adult endothelium to immunocompetent haematopoietic stem cells. Nature, 545(7655):439, 2017.
  27. Sean C Bendall, Kara L Davis, El-ad David Amir, Michelle D Tadmor, Erin F Simonds, Tiffany J Chen, Daniel K Shenfeld, Garry P Nolan, and Dana Peer. Single-cell trajectory detection uncovers progression and regulatory coordination in human b cell development. Cell, 157(3):714–725, 2014.
  28. Kieran Campbell, Chris P Ponting, and Caleb Webber. Laplacian eigenmaps and principal curves for high resolution pseudotemporal ordering of single-cell rna-seq profiles. bioRxiv preprint, page 027219, 2015.
  29. Jaehoon Shin, Daniel A Berg, Yunhua Zhu, Joseph Y Shin, Juan Song, Michael A Bonaguidi, Grigori Enikolopov, David W Nauen, Kimberly M Christian, Guo-li Ming, et al. Single-cell rna-seq with waterfall reveals molecular cascades underlying adult neurogenesis. Cell Stem Cell, 17(3):360–372, 2015.
  30. Xiaojie Qiu, Andrew Hill, Yi-An Ma, and Cole Trapnell. Single-cell mrna quantification and differential analysis with census. Nat Meth, pages 309–315, 2016.
  31. Kelly Street, Davide Risso, Russell B Fletcher, Diya Das, John Ngai, Nir Yosef, Elizabeth Purdom, and Sandrine Dudoit. Slingshot: cell lineage and pseudotime inference for single-cell transcriptomics. BMC genomics, 19(1):477, 2018.
  32. Manu Setty, Michelle D Tadmor, Shlomit Reich-Zeliger, Omer Angel, Tomer Meir Salame, Pooja Kathail, Kristy Choi, Sean Bendall, Nir Friedman, and Dana Pe’er. Wishbone identifies bifurcating developmental trajectories from single-cell data. Nature biotechnology, 34(6):637, 2016.
  33. Alexander N Gorban and Andrei Y Zinovyev. Principal graphs and manifolds. In Handbook of research on machine learning applications and trends: algorithms, methods, and techniques, pages 28–59. IGI Global, 2010.
  34. Jing Yang, Christopher A Penfold, Murray R Grant, and Magnus Rattray. Inferring the perturbation time from biological time course data. Bioinformatics, 32(19):2956–2964, 2016.
  35. Carl Edward Rasmussen and Christopher KI Williams. Gaussian processes for machine learning. MIT press Cambridge, 2006.
  36. Alexis Boukouvalas, James Hensman, and Magnus Rattray. BGP: identifying gene-specific branching dynamics from single-cell data with a branching gaussian process. Genome biology, 19(1):65, 2018.
Index Terms

Computer Science
Information Sciences

Keywords

Single-cell gene expression pseudotime trajectory branching