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      SPRING: a kinetic interface for visualizing high dimensional single-cell expression data

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      , ,
      Bioinformatics
      Oxford University Press

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          Abstract

          Motivation

          Single-cell gene expression profiling technologies can map the cell states in a tissue or organism. As these technologies become more common, there is a need for computational tools to explore the data they produce. In particular, visualizing continuous gene expression topologies can be improved, since current tools tend to fragment gene expression continua or capture only limited features of complex population topologies.

          Results

          Force-directed layouts of k-nearest-neighbor graphs can visualize continuous gene expression topologies in a manner that preserves high-dimensional relationships and captures complex population topologies. We describe SPRING, a pipeline for data filtering, normalization and visualization using force-directed layouts and show that it reveals more detailed biological relationships than existing approaches when applied to branching gene expression trajectories from hematopoietic progenitor cells and cells of the upper airway epithelium. Visualizations from SPRING are also more reproducible than those of stochastic visualization methods such as tSNE, a state-of-the-art tool. We provide SPRING as an interactive web-tool with an easy to use GUI.

          Supplementary information

          Supplementary data are available at Bioinformatics online.

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          Most cited references2

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          Characterization of the single-cell transcriptional landscape by highly multiplex RNA-seq.

          Our understanding of the development and maintenance of tissues has been greatly aided by large-scale gene expression analysis. However, tissues are invariably complex, and expression analysis of a tissue confounds the true expression patterns of its constituent cell types. Here we describe a novel strategy to access such complex samples. Single-cell RNA-seq expression profiles were generated, and clustered to form a two-dimensional cell map onto which expression data were projected. The resulting cell map integrates three levels of organization: the whole population of cells, the functionally distinct subpopulations it contains, and the single cells themselves-all without need for known markers to classify cell types. The feasibility of the strategy was demonstrated by analyzing the transcriptomes of 85 single cells of two distinct types. We believe this strategy will enable the unbiased discovery and analysis of naturally occurring cell types during development, adult physiology, and disease.
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            Diffusion maps for high-dimensional single-cell analysis of differentiation data.

            Single-cell technologies have recently gained popularity in cellular differentiation studies regarding their ability to resolve potential heterogeneities in cell populations. Analyzing such high-dimensional single-cell data has its own statistical and computational challenges. Popular multivariate approaches are based on data normalization, followed by dimension reduction and clustering to identify subgroups. However, in the case of cellular differentiation, we would not expect clear clusters to be present but instead expect the cells to follow continuous branching lineages.
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              Author and article information

              Contributors
              Role: Associate Editor
              Journal
              Bioinformatics
              Bioinformatics
              bioinformatics
              Bioinformatics
              Oxford University Press
              1367-4803
              1367-4811
              01 April 2018
              07 December 2017
              07 December 2017
              : 34
              : 7
              : 1246-1248
              Affiliations
              Department of Systems Biology, Harvard Medical School, Boston, MA, USA
              Author notes
              To whom correspondence should be addressed. Email: calebsw@ 123456gmail.com or allon_klein@ 123456hms.harvard.edu
              Article
              btx792
              10.1093/bioinformatics/btx792
              6030950
              29228172
              d2dc19c7-f32a-4638-8c55-75938eb1f129
              © The Author 2017. Published by Oxford University Press.

              This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

              History
              : 01 August 2017
              : 18 October 2017
              : 05 December 2017
              Page count
              Pages: 3
              Funding
              Funded by: NIH 10.13039/100000002
              Award ID: 5T32GM080177-07
              Funded by: NIH 10.13039/100000002
              Award ID: 1R33CA212697
              Categories
              Applications Notes
              Gene Expression

              Bioinformatics & Computational biology
              Bioinformatics & Computational biology

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