Computational Modeling of the Main Signaling Pathways Involved in Mast Cell Activation

Abstract

A global and rigorous understanding of the signaling pathways and cross-regulatory processes involved in mast cell activation requires the integration of published information with novel functional datasets into a comprehensive computational model. Based on an exhaustive curation of the existing literature and using the software CellDesigner, we have built and annotated a comprehensive molecular map for the FcεRI signaling network. This map can be used to visualize and interpret high-throughput expression data. Furthermore, leaning on this map and using the logical modeling software GINsim, we have derived a qualitative dynamical model, which recapitulates the most salient features of mast cell activation. The resulting logical model can be used to explore the dynamical properties of the system and its responses to different stimuli, in normal or mutant conditions.

Automated inference of Boolean models from molecular interaction maps using CaSQ

“…7a ) and Syk ( Fig. 7b ) knockout experiments described in the publication ( Niarakis et al , 2014 ).…”

“…For testing the applicability of CaSQ, we used various molecular interaction maps that differ in size, complexity and use of SBGN notation, as shown in Table 1 . Namely, we used one molecular interaction map comprising 125 nodes describing mast cell activation ( Niarakis et al , 2014 ), one map comprising 232 nodes for MAPK activation ( Grieco et al , 2013 ), one for cholecystokinin signaling with 530 nodes ( Tripathi et al , 2015 ) and finally two large-scale molecular maps, one for rheumatoid arthritis (RA)—the only SBGN-compliant—( Singh et al , 2018 , 2020 ) comprising 779 nodes, detailed annotations and references in the MIRIAM and text annotation section of the CellDesigner file ( Funahashi et al , 2003 ) ( Supplementary Fig. S2 ) and the Alzheimer’s pathway map with 1361 nodes ( Ogishima et al , 2016 ).…”

“…Molecular interaction maps can be used to describe biological mechanisms concisely and effectively. Various molecular maps describing different biological processes ( Caron et al , 2010 ; Fujita et al , 2014 ; Grieco et al , 2013 ; Jagannadham et al , 2016 ; Kuperstein et al , 2015 ; Mazein et al , 2018 ; Niarakis et al , 2014 ; Ogishima et al , 2016 ; Singh et al , 2018 ; Tripathi et al , 2015 ; Singh et al ., 2020 ) have been published, and initiatives have emerged, such as the Disease Maps Project ( http://disease-maps.org ), demonstrating the utility and need of this type of representation of biological knowledge ( Mazein et al , 2018 ; Ostaszewski et al , 2019 ). Molecular interaction maps can serve as a stand-alone knowledge base, or they can be used as a scaffold for building computational models.…”

Complex Stability and an Irrevertible Transition Reverted by Peptide and Fibroblasts in a Dynamic Model of Innate Immunity

“…Although from the perspective of understanding the immune response, innate immunity has already been proposed a while ago to be most suitable for systems biology studies (10), the number of mathematical models focusing on this innate immunity is still limited (22), yet the innate immune system plays an important role in effective host defense against bacterial and viral infections (23,24) and possibly in allergies and tumorigenesis, and there may already be sufficient information to construct explicit mechanism-based systems biology models. A comprehensive map of IgE-mediated mast cell activation (25) might be used to explore both the intracellular and population dynamical properties of the corresponding section of the immune system, and the experimental field is now reporting genomewide experimental data sets, which systems biology can integrate and help understand in terms of the emergence of function (10). One pipeline of already existing mathematical models of innate immunity has only four, rather abstract, variables, i.e., "inflammation, " "damage, " "initiating event, " and "antiinflammation" (26).…”

Application of Atlas of Cancer Signalling Network in pre-clinical studies

“…The navigation interface include features such as scrolling, zooming, markers and callouts using Google Maps technology adapted by NaviCell [14] ( Figure 3), web-based platform supporting ACSN and similar efforts in CellDesigner format [15,16] or other formats [17]. The semantic zooming in NaviCell (http://navicell.curie.fr), provides several view levels, achieved by gradual exclusion of details and abstraction of information upon zooming out ( Figure 2B).…”