PyMINEr Finds Gene and Autocrine-Paracrine Networks from Human Islet scRNA-Seq

Scott R Tyler; Pavana G Rotti; Xingshen Sun; Yaling Yi; Weiliang Xie; Michael C Winter; Miles J Flamme-Wiese; Budd A Tucker; Robert F Mullins; Andrew W Norris; John F Engelhardt

doi:10.1016/j.celrep.2019.01.063

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PyMINEr Finds Gene and Autocrine-Paracrine Networks from Human Islet scRNA-Seq

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PyMINEr Finds Gene and Autocrine-Paracrine Networks from Human Islet scRNA-Seq

Scott R Tyler, Pavana G Rotti, Xingshen Sun, Yaling Yi, Weiliang Xie, Michael C Winter, Miles J Flamme-Wiese, Budd A Tucker, Robert F Mullins, Andrew W Norris, …

Cell reports (Cambridge), Vol.26(7), pp.1951-1964.e8

02/12/2019

DOI: 10.1016/j.celrep.2019.01.063

PMCID: PMC6394844

PMID: 30759402

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Abstract

Toolsets available for in-depth analysis of scRNA-seq datasets by biologists with little informatics experience is limited. Here, we describe an informatics tool (PyMINEr) that fully automates cell type identification, cell type-specific pathway analyses, graph theory-based analysis of gene regulation, and detection of autocrine-paracrine signaling networks in silico . We applied PyMINEr to interrogate human pancreatic islet scRNA-seq datasets and discovered several features of co-expression graphs, including concordance of scRNA-seq-graph structure with both protein-protein interactions and 3D genomic architecture, association of high-connectivity and low-expression genes with cell type enrichment, and potential for the graph structure to clarify potential etiologies of enigmatic disease-associated variants. We further created a consensus co-expression network and autocrine-paracrine signaling networks within and across islet cell types from seven datasets. PyMINEr correctly identified changes in BMP-WNT signaling associated with cystic fibrosis pancreatic acinar cell loss. This proof-of-principle study demonstrates that the PyMINEr framework will be a valuable resource for scRNA-seq analyses. Tyler et al. create PyMINEr, an open-source program ( https://www.sciencescott.com/pyminer ) that automates analyses of expression datasets without coding. These analyses include clustering, differential expression, pathway analyses, co-expression networks, marker gene identification, and autocrine-paracrine signaling prediction. Integration of seven datasets shows elevated BMP-WNT signaling in cystic fibrosis pancreata.

Details

Title: Subtitle: PyMINEr Finds Gene and Autocrine-Paracrine Networks from Human Islet scRNA-Seq
Creators: Scott R Tyler - Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Pavana G Rotti - Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Xingshen Sun - Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Yaling Yi - Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Weiliang Xie - Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Michael C Winter - Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Miles J Flamme-Wiese - Institute for Vision Research, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Budd A Tucker - Institute for Vision Research, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Robert F Mullins - Institute for Vision Research, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Andrew W Norris - Center for Gene Therapy, University of Iowa Carver College of Medicine, Iowa City, IA, USA
John F Engelhardt - Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Resource Type: Journal article
Publication Details: Cell reports (Cambridge), Vol.26(7), pp.1951-1964.e8
DOI: 10.1016/j.celrep.2019.01.063
PMID: 30759402
PMCID: PMC6394844
ISSN: 2211-1247
eISSN: 2211-1247
Grant note: name: University of Iowa Carver College of Medicine; DOI: 10.13039/100000002, name: NIH, award: R24 DK096518, R24 HL123482, R01 DK115791; name: Fraternal Order of Eagles Diabetes Research Center; DOI: 10.13039/100011352, name: University of Iowa Center for Gene Therapy, award: DK54759; name: Carver Chair in Molecular Medicine; DOI: 10.13039/100000002, name: NIH; DOI: 10.13039/100000057, name: NIGMS, award: T32GM082729
Language: English
Date published: 02/12/2019
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Endocrinology and Diabetes; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Radiation Oncology; Biochemistry and Molecular Biology; Internal Medicine; Ophthalmology and Visual Sciences
Record Identifier: 9984025310202771

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