Title
Conceptual and computational framework for logical modelling of biological networks deregulated in diseases.
Abstract
Mathematical models can serve as a tool to formalize biological knowledge from diverse sources, to investigate biological questions in a formal way, to test experimental hypotheses, to predict the effect of perturbations and to identify underlying mechanisms. We present a pipeline of computational tools that performs a series of analyses to explore a logical model's properties. A logical model of initiation of the metastatic process in cancer is used as a transversal example. We start by analysing the structure of the interaction network constructed from the literature or existing databases. Next, we show how to translate this network into a mathematical object, specifically a logical model, and how robustness analyses can be applied to it. We explore the visualization of the stable states, defined as specific attractors of the model, and match them to cellular fates or biological read-outs. With the different tools we present here, we explain how to assign to each solution of the model a probability and how to identify genetic interactions using mutant phenotype probabilities. Finally, we connect the model to relevant experimental data: we present how some data analyses can direct the construction of the network, and how the solutions of a mathematical model can also be compared with experimental data, with a particular focus on high-throughput data in cancer biology. A step-by-step tutorial is provided as a Supplementary Material and all models, tools and scripts are provided on an accompanying website: https://github.com/sysbio-curie/Logical_modelling_pipeline.
Year
DOI
Venue
2019
10.1093/bib/bbx163
BRIEFINGS IN BIOINFORMATICS
Keywords
Field
DocType
pipeline of tools,logical modelling,genetic interaction,robustness analysis,data integration,step-by-step tutorial
Data science,Data mining,Biology,Biological network
Journal
Volume
Issue
ISSN
20
4
1467-5463
Citations 
PageRank 
References 
0
0.34
29
Authors
7
Name
Order
Citations
PageRank
Arnau Montagud1222.35
Pauline Traynard211.03
Loredana Martignetti371.29
Eric Bonnet414810.86
Emmanuel Barillot5950165.00
Andrei Zinovyev628227.30
Laurence Calzone727617.90