A Bayesian Approach to Optimizing Stem Cell Cryopreservation protocols

Abstract

Cryopreservation is beset with the challenge of protocol alignment across a wide range of cell types and process variables. By taking a cross-sectional assessment of previously published cryopreservation data (sample means and standard errors) as preliminary meta-data, a decision tree learning analysis (DTLA) was performed to develop an understanding of target survival and optimized pruning methods based on different approaches. Briefly, a clear direction on the decision process for selection of methods was developed with key choices being the cooling rate, plunge temperature on the one hand and biomaterial choice, use of composites (sugars and proteins), loading procedure and cell location in 3D scaffold on the other. Secondly, using machine learning and generalized approaches via the Na\"ive Bayes Classification (NBC) approach, these metadata were used to develop posterior probabilities for combinatorial approaches that were implicitly recorded in the metadata. These latter results showed that newer protocol choices developed using probability elicitation techniques can unearth improved protocols consistent with multiple unidimensional optimized physical protocols. In conclusion, this article proposes the use of DTLA models and subsequently NBC for the improvement of modern cryopreservation techniques through an integrative approach. Keywords: 3D cryopreservation, decision-tree learning (DTL), sugars, mouse embryonic stem cells, meta-data, Na\"ive Bayes Classifier (NBC)