Platform-agnostic CellNet enables cross-study analysis of cell fate engineering protocols

• DOI: 10.1016/j.stemcr.2023.06.008
• Publication Date: 2023-07-20T15:37:01Z
• Authors: Emily K.W. Lo; Jeremy J. Velazquez; Da Peng; Chulan Kwon; Mo R. Ebrahimkhani; Patrick Cahan
• Keywords: Resource; Hepatocytes; Cell Differentiation; Myocytes, Cardiac; Cell Engineering; Software

Optimization of cell engineering protocols requires standard, comprehensive quality metrics. We previously developed CellNet, a computational tool to quantitatively assess the transcriptional fidelity engineered cells compared with their natural counterparts, based on bulk-derived expression profiles. However, this platform and others were limited in ability compare data from different sources, no current makes it easy new existing state-of-the-art standardized manner. Here, we utilized our prior application top-scoring pair transformation build platform, platform-agnostic CellNet (PACNet), address both shortcomings. To demonstrate utility PACNet, applied thousands samples over 100 studies that describe dozens designed produce seven distinct types. performed an in-depth examination hepatocyte cardiomyocyte identify best-performing methods, characterize extent intra-protocol inter-lab variation, common off-target signatures, including surprising neural/neuroendocrine signature primary liver-derived organoids. have made PACNet available as easy-to-use web application, allowing users relative database reference samples, open-source, extensible code.