2 research outputs found
A knowledge representation meta-model for rule-based modelling of signalling networks
The study of cellular signalling pathways and their deregulation in disease
states, such as cancer, is a large and extremely complex task. Indeed, these
systems involve many parts and processes but are studied piecewise and their
literatures and data are consequently fragmented, distributed and sometimes--at
least apparently--inconsistent. This makes it extremely difficult to build
significant explanatory models with the result that effects in these systems
that are brought about by many interacting factors are poorly understood.
The rule-based approach to modelling has shown some promise for the
representation of the highly combinatorial systems typically found in
signalling where many of the proteins are composed of multiple binding domains,
capable of simultaneous interactions, and/or peptide motifs controlled by
post-translational modifications. However, the rule-based approach requires
highly detailed information about the precise conditions for each and every
interaction which is rarely available from any one single source. Rather, these
conditions must be painstakingly inferred and curated, by hand, from
information contained in many papers--each of which contains only part of the
story.
In this paper, we introduce a graph-based meta-model, attuned to the
representation of cellular signalling networks, which aims to ease this massive
cognitive burden on the rule-based curation process. This meta-model is a
generalization of that used by Kappa and BNGL which allows for the flexible
representation of knowledge at various levels of granularity. In particular, it
allows us to deal with information which has either too little, or too much,
detail with respect to the strict rule-based meta-model. Our approach provides
a basis for the gradual aggregation of fragmented biological knowledge
extracted from the literature into an instance of the meta-model from which we
can define an automated translation into executable Kappa programs.Comment: In Proceedings DCM 2015, arXiv:1603.0053