comunicación de congreso
Hybrid mathematical modeling decodes the complexity of sphingolipid pathway to predict chemosensitivity
Fecha
2017Registro en:
10.1109/IWOBI.2017.7985532
Autor
Molina Mora, José Arturo
Quirós Barrantes, Steve
Kop Montero, Mariana
Mora Rodríguez, Rodrigo Antonio
Crespo Mariño, Juan Luis
Institución
Resumen
Sphingolipid (SL) signaling pathway is a complex
biological system able to integrate different types of cellular
stress signals related to induction of cell death pathways with
special interest in cancer. This makes of the SL pathway a
promising sensor of chemosensitivity and a target hub to
overcome resistance. However, it is unclear how
chemotherapeutic drugs can disturb the SL pathway and how the
SL content modulates cellular fate. A hybrid mathematical model
was proposed in order to integrate i) the metabolism of SL
analogue (SM-BODIPY) modeled by an ordinary differential
equation (ODE) approach, ii) a Gaussian mixture model (GMM)
of the fluorescence features to identify how the SL pathway
senses the effect of chemotherapeutic drugs and iii) a fuzzy logic
model (FLM) to associate SL composition with cell viability by
semi-quantitative rules. Altogether, this hybrid model approach
was able to predict the cell viability of double experimental
perturbations with chemotherapy, indicating that the SL
pathway is a promising sensor to design strategies to overcome
drug resistance in cancer.