Dpath software reveals hierarchical haemato-endothelial lineages of Etv2 progenitors based on single-cell transcriptome analysis.
Developmental, stem cell and cancer biologists are interested in the molecular definition of cellular differentiation. Although single-cell RNA sequencing represents a transformational advance for global gene analyses, novel obstacles have emerged, including the computational management of dropout events, the reconstruction of biological pathways and the isolation of target cell populations. We develop an algorithm named dpath that applies the concept of metagene entropy and allows the ranking of cells based on their differentiation potential. We also develop self-organizing map (SOM) and random walk with restart (RWR) algorithms to separate the progenitors from the differentiated cells and reconstruct the lineage hierarchies in an unbiased manner. We test these algorithms using single cells from Etv2-EYFP transgenic mouse embryos and reveal specific molecular pathways that direct differentiation programmes involving the haemato-endothelial lineages. This software program quantitatively assesses the progenitor and committed states in single-cell RNA-seq data sets in a non-biased manner.
Lillehei Heart Institute, University of Minnesota, 2231 6th St S.E, 4-165 CCRB, Minneapolis, Minnesota 55114, USA.
Wuming
0000-0002-3147-4028
W
Gong
Lillehei Heart Institute, University of Minnesota, 2231 6th St S.E, 4-165 CCRB, Minneapolis, Minnesota 55114, USA.
Tara L
TL
Rasmussen
Lillehei Heart Institute, University of Minnesota, 2231 6th St S.E, 4-165 CCRB, Minneapolis, Minnesota 55114, USA.
Bhairab N
BN
Singh
Lillehei Heart Institute, University of Minnesota, 2231 6th St S.E, 4-165 CCRB, Minneapolis, Minnesota 55114, USA.
Naoko
N
Koyano-Nakagawa
Division of Biostatistics, School of Public Health, University of Minnesota, 420 Delaware St S.E., Mayo Building A302, Minneapolis, Minnesota 55455, USA.
Wei
W
Pan
Lillehei Heart Institute, University of Minnesota, 2231 6th St S.E, 4-165 CCRB, Minneapolis, Minnesota 55114, USA.
Daniel J
DJ
Garry
D000465:Algorithms; D000818:Animals; D002449:Cell Aggregation; D019070:Cell Lineage / Q000235:genetics*; D002469:Cell Separation; D016000:Cluster Analysis; D058732:Embryoid Bodies / Q000166:cytology; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D015203:Reproducibility of Results; D017423:Sequence Analysis, RNA; D059010:Single-Cell Analysis; D012984:Software; D014157:Transcription Factors / Q000378:metabolism*; D059467:Transcriptome / Q000235:genetics
C503994:ER71 protein, mouse; D014157:Transcription Factors