Analysis of Pattern Formation by Colored Petri Nets With Quantitative Regulation of Gene Expression Level.
IEEE/ACM Trans Comput Biol Bioinform
; 19(1): 317-327, 2022.
Article
en En
| MEDLINE
| ID: mdl-32750877
ABSTRACT
Modeling and simulation are becoming indispensable tools for studying multicellular events such as pattern formation during embryonic development. In this paper, we propose a new approach for analyzing multicellular biological phenomena by combining colored hybrid Petri nets (ColHPNs) with newly devised biological experiments that can control level of a gene quantitatively. With this approach, we analyzed patterning of the boundary cells in the Drosophila large intestine, where one-cell-wide domain of boundary cells differentiate through Delta-Notch signaling. Biological experiments regulating the level of Delta resulted in six distinct patterns of boundary cells correlating with the level of Delta. All these patterns were successfully reproduced by simulation based on ColHPN modeling only by changing the parameter related to the level of Delta. By monitoring the concentration of the active form of Notch in each cell during simulation, it was revealed that these distinct modes of patterning correlate with the fluctuation range of active Notch. Combination of simulation and quantitative manipulation of a gene activity described here is a reliable and powerful approach for analyzing and understanding the patterning process regulated by Notch signaling. This approach can be easily adapted to address other similar pattern formation issues in the systems biology area.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas de Drosophila
/
Drosophila
Límite:
Animals
Idioma:
En
Revista:
ACM Trans Comput Biol Bioinform
Asunto de la revista:
BIOLOGIA
/
INFORMATICA MEDICA
Año:
2022
Tipo del documento:
Article