Predicting cell behaviour parameters from glioblastoma on a chip images. A deep learning approach

The broad possibilities offered by microfluidic devices in relation to massive data monitoring and acquisition open the door to the use of deep learning technologies in a very promising field: cell culture monitoring. In this work, we develop a methodology for parameter identification in cell culture from fluorescence images using Convolutional Neural Networks (CNN). We apply this methodology to the in vitro study of glioblastoma (GBM), the most common, aggressive and lethal primary brain tumour. In particular, the aim is to predict the three parameters defining the go or grow GBM behaviour, which is determinant for the tumour prognosis and response to treatment. The data used to train the network are obtained from a mathematical model, previously validated with in vitro experimental results. The resulting CNN provides remarkably accurate predictions (Pearson''s ¿ > 0.99 for all the parameters). Besides, it proves to be sound, to filter noise and to generalise. After training and validation with synthetic data, we predict the parameters corresponding to a real image of a microfluidic experiment. The obtained results show good performance of the CNN. The proposed technique may set the first steps towards patient-specific tools, able to predict in real-time the tumour evolution for each particular patient, thanks to a combined in vitro-in silico approach. © 2021 The Author(s

Analysis of the parametric correlation in mathematical modeling of in vitro glioblastoma evolution using copulas

Modeling and simulation are essential tools for better understanding complex biological processes, such as cancer evolution. However, the resulting mathematical models are often highly non-linear and include many parameters, which, in many cases, are difficult to estimate and present strong correlations. Therefore, a proper parametric analysis is mandatory. Following a previous work in which we modeled the in vitro evolution of Glioblastoma Multiforme (GBM) under hypoxic conditions, we analyze and solve here the problem found of parametric correlation. With this aim, we develop a methodology based on copulas to approximate the multidimensional probability density function of the correlated parameters. Once the model is defined, we analyze the experimental setting to optimize the utility of each configuration in terms of gathered information. We prove that experimental configurations with oxygen gradient and high cell concentration have the highest utility when we want to separate correlated effects in our experimental design. We demonstrate that copulas are an adequate tool to analyze highly-correlated multiparametric mathematical models such as those appearing in Biology, with the added value of providing key information for the optimal design of experiments, reducing time and cost in in vivo and in vitro experimental campaigns, like those required in microfluidic models of GBM evolution