Systematically predict the transcriptomic switches required
to produce any target cell type from any source cell type.
The MOGRIFY® technology was developed as a systematic means of identifying the key regulatory switches, such as an optimal combination of transcription factors, required to drive cell identity. The platform can be used to enhance existing stem-cell forward reprogramming methods or can bypass development pathways altogether, affecting a direct transdifferentiation between a mature cell type to another mature cell type.
The figure below shows the step-wise scientific approach used in order to achieve such predictions. Firstly, the gene expression levels are compared in the source and target cell types (consisting of FANTOM5 and other proprietary data). This step determines the changes in the gene expression levels that are needed in order to achieve the conversion. Secondly, transcription factors are scored compared to the required changes in gene expression levels by both direct and indirect influences (using the MARA and STRING databases). This includes the regulatory network information on protein-DNA interactions as well as protein-protein interactions. Thirdly, local transcriptomic regulatory networks are built to calculate the effect of the transcription factors on gene expression levels. Lastly, the optimal combination of transcription factors is predicted to maximize network coverage, while avoiding redundancies, to achieve the necessary changes in gene expression for the cell conversion to occur.
In addition to identifying transcription factor-driven cell conversions, small molecules that are known to affect the expression of the key predicted transcription factors can be identified from published literature to create a small molecule conversion cocktail. This has the added benefit of not requiring the transduction of the transcription factors and consequently holds greater potential as an in vivo reprogramming therapy.