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Methods Mol Biol. 2019;1975:427-454. doi: 10.1007/978-1-4939-9224-9_19.

Cell Fate Engineering Tools for iPSC Disease Modeling.

Lo EKW1,2, Cahan P3,4.

Author information

1
Institute for Cell Engineering, Johns Hopkins University, Baltimore, MD, USA.
2
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
3
Institute for Cell Engineering, Johns Hopkins University, Baltimore, MD, USA. patrick.cahan@jhmi.edu.
4
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA. patrick.cahan@jhmi.edu.

Abstract

The field of cell fate engineering is contingent on tools that can quantitatively assess the efficacy of cell fate engineering protocols and experiments. CellNet is such a cell fate assessment tool that utilizes network biology to both evaluate and suggest candidate transcriptional regulatory modifications to improve the similarity of an engineered population to its corresponding in vivo target population. CellNet takes in expression profiles in the form of RNA-sequencing data and generates several metrics of cell identity and protocol efficacy. In this chapter, we demonstrate how to (1) preprocess raw RNA-sequencing data to generate an expression matrix, (2) train CellNet using preprocessed expression matrices, and (3) apply CellNet to a query study and interpret its results. We demonstrate the utility of CellNet for analysis of iPSC disease modeling studies, which we evaluate through the lens of cell fate engineering.

KEYWORDS:

Cell fate engineering; Computational biology; Disease modeling; Gene expression profiling; Gene regulatory networks; Stem cells

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