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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.
The increasing accessibility of single cell omics technologies beyond transcriptomics demands parallel advances in analysis. Here, the authors introduce STREAM, a pipeline for reconstruction and visualization of differentiation trajectories from both single-cell RNA-seq and ATAC-seq data.
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1 Massachusetts General Hospital Research Institute and Harvard Medical School, Molecular Pathology Unit & Cancer Center, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Dana-Farber Cancer Institute, Department of Biostatistics and Computational Biology, Boston, USA (GRID:grid.65499.37) (ISNI:0000 0001 2106 9910); Harvard T.H. Chan School of Public Health, Department of Biostatistics, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); Tongji University, Department of Computer Science and Technology, Shanghai, China (GRID:grid.24516.34) (ISNI:0000000123704535)
2 PSL Research University, Institut Curie, Paris, France (GRID:grid.440907.e) (ISNI:0000 0004 1784 3645); INSERM, U900, Paris, France (GRID:grid.418596.7) (ISNI:0000 0004 0639 6384); PSL Research University, CBIO-Centre for Computational Biology, MINES ParisTech, Paris, France (GRID:grid.440907.e) (ISNI:0000 0004 1784 3645)
3 Massachusetts General Hospital Research Institute and Harvard Medical School, Molecular Pathology Unit & Cancer Center, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Massachusetts Institute of Technology, Department of Biological Engineering, Cambridge, USA (GRID:grid.116068.8) (ISNI:0000 0001 2341 2786)
4 Massachusetts General Hospital Research Institute and Harvard Medical School, Molecular Pathology Unit & Cancer Center, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Broad Institute of MIT and Harvard, Cambridge, USA (GRID:grid.66859.34)
5 University of Palermo, Department of Mathematics and Computer Science, Palermo, Italy (GRID:grid.10776.37) (ISNI:0000 0004 1762 5517); Euro-Mediterranean Institute of Science and Technology, Department of Sciences for technological innovation, Palermo, Italy (GRID:grid.428936.2)
6 Tongji University, Department of Computer Science and Technology, Shanghai, China (GRID:grid.24516.34) (ISNI:0000000123704535)
7 Fudan University, Shanghai Key Lab of Intelligent Information Processing, and School of Computer Science, Shanghai, China (GRID:grid.8547.e) (ISNI:0000 0001 0125 2443)
8 University of Leicester, Department of Mathematics, Leicester, UK (GRID:grid.9918.9) (ISNI:0000 0004 1936 8411); Lobachevsky University, Nizhni Novgorod, Russia (GRID:grid.28171.3d) (ISNI:0000 0001 0344 908X)
9 Broad Institute of MIT and Harvard, Cambridge, USA (GRID:grid.66859.34); Harvard Medical School, Division of Hematology/Oncology, Boston Children’s Hospital, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Department of Pediatrics, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X)
10 Massachusetts General Hospital Research Institute and Harvard Medical School, Molecular Pathology Unit & Cancer Center, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Harvard T.H. Chan School of Public Health, Department of Biostatistics, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); Broad Institute of MIT and Harvard, Cambridge, USA (GRID:grid.66859.34)
11 Massachusetts General Hospital Research Institute and Harvard Medical School, Molecular Pathology Unit & Cancer Center, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924); Harvard Stem Cell Institute, Cambridge, USA (GRID:grid.38142.3c) (ISNI:000000041936754X)
12 PSL Research University, Institut Curie, Paris, France (GRID:grid.440907.e) (ISNI:0000 0004 1784 3645); INSERM, U900, Paris, France (GRID:grid.418596.7) (ISNI:0000 0004 0639 6384); PSL Research University, CBIO-Centre for Computational Biology, MINES ParisTech, Paris, France (GRID:grid.440907.e) (ISNI:0000 0004 1784 3645); Lobachevsky University, Nizhni Novgorod, Russia (GRID:grid.28171.3d) (ISNI:0000 0001 0344 908X)
13 Broad Institute of MIT and Harvard, Cambridge, USA (GRID:grid.66859.34); Harvard University, Harvard Society of Fellows, Cambridge, USA (GRID:grid.38142.3c) (ISNI:000000041936754X)
14 Dana-Farber Cancer Institute, Department of Biostatistics and Computational Biology, Boston, USA (GRID:grid.65499.37) (ISNI:0000 0001 2106 9910); Harvard T.H. Chan School of Public Health, Department of Biostatistics, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); Harvard Stem Cell Institute, Cambridge, USA (GRID:grid.38142.3c) (ISNI:000000041936754X)