Single-cell trajectories reconstruction, exploration and mapping of omics data with STREAM

Huidong Chen; Luca Albergante; Jonathan Y Hsu; Caleb A Lareau; Giosuè Lo Bosco; Jihong Guan; Shuigeng Zhou; Alexander N Gorban; Daniel E Bauer; Martin J Aryee; David M Langenau; Andrei Zinovyev; Jason D Buenrostro; Guo-Cheng Yuan; Luca Pinello

doi:10.1038/s41467-019-09670-4

Single-cell trajectories reconstruction, exploration and mapping of omics data with STREAM

Nat Commun. 2019 Apr 23;10(1):1903. doi: 10.1038/s41467-019-09670-4.

Authors

Huidong Chen^{1

2

3

4}, Luca Albergante^{5

6

7}, Jonathan Y Hsu^{1

8}, Caleb A Lareau^{1

9}, Giosuè Lo Bosco^{10

11}, Jihong Guan⁴, Shuigeng Zhou¹², Alexander N Gorban^{13

14}, Daniel E Bauer^{9

15}, Martin J Aryee^{1

3

9}, David M Langenau^{1

16}, Andrei Zinovyev^{5

6

7

14}, Jason D Buenrostro^{9

17}, Guo-Cheng Yuan^{18

19

20}, Luca Pinello^{21

22}

Affiliations

¹ Molecular Pathology Unit & Cancer Center, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, 02114, USA.
² Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
³ Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, 02215, USA.
⁴ Department of Computer Science and Technology, Tongji University, 201804, Shanghai, China.
⁵ Institut Curie, PSL Research University, F-75005, Paris, France.
⁶ INSERM, U900, F-75005, Paris, France.
⁷ MINES ParisTech, PSL Research University, CBIO-Centre for Computational Biology, F-75006, Paris, France.
⁸ Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁹ Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
¹⁰ Department of Mathematics and Computer Science, University of Palermo, 90123, Palermo, Italy.
¹¹ Department of Sciences for technological innovation, Euro-Mediterranean Institute of Science and Technology, 90139, Palermo, Italy.
¹² Shanghai Key Lab of Intelligent Information Processing, and School of Computer Science, Fudan University, 200433, Shanghai, China.
¹³ Department of Mathematics, University of Leicester, University Road, Leicester, LE1 7RH, UK.
¹⁴ Lobachevsky University, Nizhni Novgorod, 603022, Russia.
¹⁵ Division of Hematology/Oncology, Boston Children's Hospital, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Department of Pediatrics, Harvard Medical School, Boston, MA, 02215, USA.
¹⁶ Harvard Stem Cell Institute, Cambridge, MA, 02138, USA.
¹⁷ Harvard Society of Fellows, Harvard University, Cambridge, MA, 02138, USA.
¹⁸ Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA. gcyuan@jimmy.harvard.edu.
¹⁹ Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, 02215, USA. gcyuan@jimmy.harvard.edu.
²⁰ Harvard Stem Cell Institute, Cambridge, MA, 02138, USA. gcyuan@jimmy.harvard.edu.
²¹ Molecular Pathology Unit & Cancer Center, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, 02114, USA. lpinello@mgh.harvard.edu.
²² Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA. lpinello@mgh.harvard.edu.

Abstract

Single-cell transcriptomic assays have enabled the de novo reconstruction of lineage differentiation trajectories, along with the characterization of cellular heterogeneity and state transitions. Several methods have been developed for reconstructing developmental trajectories from single-cell transcriptomic data, but efforts on analyzing single-cell epigenomic data and on trajectory visualization remain limited. Here we present STREAM, an interactive pipeline capable of disentangling and visualizing complex branching trajectories from both single-cell transcriptomic and epigenomic data. We have tested STREAM on several synthetic and real datasets generated with different single-cell technologies. We further demonstrate its utility for understanding myoblast differentiation and disentangling known heterogeneity in hematopoiesis for different organisms. STREAM is an open-source software package.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Algorithms*
Animals
Cell Differentiation
Cell Lineage / genetics*
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism
Erythroid Cells / cytology
Erythroid Cells / metabolism
GATA1 Transcription Factor / genetics
GATA1 Transcription Factor / metabolism
Gene Expression Regulation, Developmental
Genomics / methods*
Hematopoietic Stem Cells / cytology
Hematopoietic Stem Cells / metabolism*
Interferon Regulatory Factors / genetics
Interferon Regulatory Factors / metabolism
Lymphocytes / cytology
Lymphocytes / metabolism
Mice
Multifactor Dimensionality Reduction
Myeloid Cells / cytology
Myeloid Cells / metabolism
Myoblasts / cytology
Myoblasts / metabolism
Signal Transduction
Single-Cell Analysis / methods
Single-Cell Analysis / statistics & numerical data*
Transcription Factors / genetics
Transcription Factors / metabolism
Transcriptome*

Substances

DNA-Binding Proteins
GATA1 Transcription Factor
GFI1 protein, human
Gata1 protein, mouse
Interferon Regulatory Factors
Transcription Factors
interferon regulatory factor-8

Abstract

Publication types

MeSH terms

Substances

Grants and funding