Exploring Identifiability in Hybrid Models of Cell Signaling Pathways

Autor(es)

Sousa, Ronaldo N. ; Campos, Cristiano G. S. ; Wang, Willian ; Hashimoto, Ronaldo F. ; Armelin, Hugo A. ; Reis, Marcelo S.

• Tipo de documento: Artigo Científico
• Fonte: ADVANCES IN BIOINFORMATICS AND COMPUTATIONAL BIOLOGY, BSB 2023; v. 13954, p. 12-pg., 2023-01-01.

Resumo

Various processes, including growth, proliferation, migration, and death, mediate the activity of a cell. To better understand these processes, dynamic modeling can be a helpful tool. First-principle modeling provides interpretability, while data-driven modeling can offer predictive performance using models such as neural network, however at the expense of the understanding of the underlying biological processes. A hybrid model that combines both approaches might mitigate the limitations of each of them alone; nevertheless, to this end one needs to tackle issues such as model calibration and identifiability. In this paper, we report a methodology to address these challenges that makes use of a universal differential equation (UDE)-based hybrid modeling, were a partially known, ODE-based, first-principle model is combined with a feedforward neural network-based, data-driven model. We used a synthetic signaling network composed of 38 chemical species and 51 reactions to generate simulated time series for those species, and then defined twelve of those reactions as a partially known first-principle model. A UDE system was defined with this latter and it was calibrated with the data simulated with the whole network. Initial results showed that this approach could identify the missing communication of the partially-known first-principle model with the remainder of the network. Therefore, we expect that this type of hybrid modeling might become a powerful tool to assist in the investigation of underlying mechanisms in cellular systems. (AU)

• Processo FAPESP: 19/24580-2 - Seleção bayesiana de modelos dinâmicos de vias não isoladas de sinalização celular
• Beneficiário: Ronaldo Nogueira de Sousa
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 13/07467-1 - CeTICS - Centro de Toxinas, Imuno-Resposta e Sinalização Celular
• Beneficiário: Hugo Aguirre Armelin
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 21/04355-4 - Implementações eficientes de métodos Bayesianos para seleção de modelos de vias de sinalização celular
• Beneficiário: Willian Wang
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 15/22308-2 - Representações intermediárias em Ciência Computacional para descoberta de conhecimento
• Beneficiário: Roberto Marcondes Cesar Junior
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 19/21619-5 - Buscando as zonas de Goldilocks de vias de sinalização celular em terapia de câncer
• Beneficiário: Marcelo da Silva Reis
• Modalidade de apoio: Auxílio à Pesquisa - Regular