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IQCELL: A platform for predicting the effect of gene perturbations on developmental trajectories using single-cell RNA-seq data

Tiam Heydari, Matthew A. Langley, Cynthia Fisher, Daniel Aguilar-Hidalgo, Shreya Shukla, Ayako Yachie-Kinoshita, Michael Hughes, Kelly M. McNagny, Peter W. Zandstra
doi: https://doi.org/10.1101/2021.04.01.438014
Tiam Heydari
1School of Biomedical Engineering, University of British Columbia, Vancouver, British Columbia, Canada, V6T 1Z3
6Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada, V6T 1Z4
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Matthew A. Langley
2Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada
3Division of Biology and Bioengineering, California Institute of Technology, Pasadena, CA 91125, USA
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Cynthia Fisher
1School of Biomedical Engineering, University of British Columbia, Vancouver, British Columbia, Canada, V6T 1Z3
6Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada, V6T 1Z4
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Daniel Aguilar-Hidalgo
1School of Biomedical Engineering, University of British Columbia, Vancouver, British Columbia, Canada, V6T 1Z3
6Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada, V6T 1Z4
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Shreya Shukla
2Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada
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Ayako Yachie-Kinoshita
2Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada
4The Systems Biology Institute, Shinagawa, Tokyo, Japan
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Michael Hughes
5Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
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Kelly M. McNagny
1School of Biomedical Engineering, University of British Columbia, Vancouver, British Columbia, Canada, V6T 1Z3
5Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
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Peter W. Zandstra
1School of Biomedical Engineering, University of British Columbia, Vancouver, British Columbia, Canada, V6T 1Z3
6Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada, V6T 1Z4
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  • For correspondence: peter.zandstra@ubc.ca
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ABSTRACT

The increasing availability of single-cell RNA-sequencing (scRNA-seq) data from various developmental systems provides the opportunity to infer gene regulatory networks (GRNs) directly from data. Herein we describe IQCELL, a platform to infer, simulate, and study executable logical GRNs directly from scRNA-seq data. Such executable GRNs provide an opportunity to inform fundamental hypotheses in developmental programs and help accelerate the design of stem cell-based technologies. We first describe the architecture of IQCELL. Next, we apply IQCELL to a scRNA-seq dataset of early mouse T-cell development and show that it can infer a priori over 75% of causal gene interactions previously reported via decades of research. We will also show that dynamic simulations of the derived GRN qualitatively recapitulate the effects of the known gene perturbations on the T-cell developmental trajectory. IQCELL is applicable to many developmental systems and offers a versatile tool to infer, simulate, and study GRNs in biological systems. (https://gitlab.com/stemcellbioengineering/iqcell)

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted April 03, 2021.
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IQCELL: A platform for predicting the effect of gene perturbations on developmental trajectories using single-cell RNA-seq data
Tiam Heydari, Matthew A. Langley, Cynthia Fisher, Daniel Aguilar-Hidalgo, Shreya Shukla, Ayako Yachie-Kinoshita, Michael Hughes, Kelly M. McNagny, Peter W. Zandstra
bioRxiv 2021.04.01.438014; doi: https://doi.org/10.1101/2021.04.01.438014
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IQCELL: A platform for predicting the effect of gene perturbations on developmental trajectories using single-cell RNA-seq data
Tiam Heydari, Matthew A. Langley, Cynthia Fisher, Daniel Aguilar-Hidalgo, Shreya Shukla, Ayako Yachie-Kinoshita, Michael Hughes, Kelly M. McNagny, Peter W. Zandstra
bioRxiv 2021.04.01.438014; doi: https://doi.org/10.1101/2021.04.01.438014

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