Understanding glioblastoma invasion using physically-guided neural networks with internal variables

PLoS Comput Biol. 2022 Apr 4;18(4):e1010019. doi: 10.1371/journal.pcbi.1010019. eCollection 2022 Apr.

Abstract

Microfluidic capacities for both recreating and monitoring cell cultures have opened the door to the use of Data Science and Machine Learning tools for understanding and simulating tumor evolution under controlled conditions. In this work, we show how these techniques could be applied to study Glioblastoma, the deadliest and most frequent primary brain tumor. In particular, we study Glioblastoma invasion using the recent concept of Physically-Guided Neural Networks with Internal Variables (PGNNIV), able to combine data obtained from microfluidic devices and some physical knowledge governing the tumor evolution. The physics is introduced in the network structure by means of a nonlinear advection-diffusion-reaction partial differential equation that models the Glioblastoma evolution. On the other hand, multilayer perceptrons combined with a nodal deconvolution technique are used for learning the go or grow metabolic behavior which characterises the Glioblastoma invasion. The PGNNIV is here trained using synthetic data obtained from in silico tests created under different oxygenation conditions, using a previously validated model. The unravelling capacity of PGNNIV enables discovering complex metabolic processes in a non-parametric way, thus giving explanatory capacity to the networks, and, as a consequence, surpassing the predictive power of any parametric approach and for any kind of stimulus. Besides, the possibility of working, for a particular tumor, with different boundary and initial conditions, permits the use of PGNNIV for defining virtual therapies and for drug design, thus making the first steps towards in silico personalised medicine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Glioblastoma* / pathology
  • Humans
  • Machine Learning
  • Neoplastic Processes
  • Neural Networks, Computer
  • Physics

Grants and funding

MD and JASH gratefully acknowledge the financial support from the Spanish Ministry of Science and Innovation (MICINN) and FEDER, UE through the project PGC2018-097257-B-C31. MHD acknowledges the financial support from the Spanish Ministry of Science and Innovation (MICINN) and FEDER, through the project PID2019-106099RB-C44/AEI/10.13039/501100011033. All authors acknowledge the funding from the Government of Aragon and the Centro de Investigacion Biomedica en Red en Bioingenieria, Biomateriales y Nanomedicina (CIBER-BBN). CIBER-BBN is financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.