DeepNEU: cellular reprogramming comes of age - a machine learning platform with application to rare diseases research

Conversion of human somatic cells into induced pluripotent stem cells (iPSCs) is often an inefficient, time consuming and expensive process. Also, the tendency of iPSCs to revert to their original somatic cell type over time continues to be problematic. A computational model of iPSCs identifying genes/molecules necessary for iPSC generation and maintenance could represent a crucial step forward for improved stem cell research. The combination of substantial genetic relationship data, advanced computing hardware and powerful nonlinear modeling software could make the possibility of artificially-induced pluripotent stem cells (aiPSC) a reality. We have developed an unsupervised deep machine learning technology, called DeepNEU that is based on a fully-connected recurrent neural network architecture with one network processing layer for each input. DeepNEU was used to simulate aiPSC systems using a defined set of reprogramming transcription factors. Genes/proteins that were reported to be essential in human pluripotent stem cells (hPSC) were used for system modelling.

The Mean Squared Error (MSE) function was used to assess system learning. System convergence was defined at MSE < 0.001. The markers of human iPSC pluripotency (N = 15) were all upregulated in the aiPSC final model. These upregulated/expressed genes in the aiPSC system were entirely consistent with results obtained for iPSCs.

This research introduces and validates the potential use of aiPSCs as computer models of human pluripotent stem cell systems. Disease-specific aiPSCs have the potential to improve disease modeling, prototyping of wet lab experiments, and prediction of genes relevant and necessary for aiPSC production and maintenance for both common and rare diseases in a cost-effective manner.