RT Journal Article
SR Electronic
T1 Singular manifolds of proteomic drivers to model the evolution of inflammatory bowel disease status
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 751289
DO 10.1101/751289
A1 Ian Morilla
A1 Thibaut Léger
A1 Assiya Marah
A1 Isabelle Pic
A1 Eric Ogier-Denis
YR 2019
UL http://biorxiv.org/content/early/2019/09/01/751289.abstract
AB The conditions who denotes the presence of an immune disease are often represented by interaction graphs. These informative, but complex structures are susceptible to being perturbed at different levels. The mode in which that perturbation occurs is still of utmost importance in areas such as reprogramming therapeutics. In this sense, the overall graph architecture is well characterise by module identification. Topological overlap-related measures make possible the localisation of highly specific module regulators that can perturb other nodes, potentially causing the entire system to change behaviour or collapse. We provide a geometric framework explaining such situations in the context of inflammatory bowel diseases (IBD). IBD are important chronic disorders of the gastrointestinal tract which incidence is dramatically increasing worldwide. Our approach models different IBD status as Riemannian manifolds defined by the graph Laplacian of two high throughput proteome screenings. Identifies module regulators as singularities within the manifolds (the so-called singular manifolds). And reinterprets the characteristic IBD nonlinear dynamics as compensatory responses to perturbations on those singularities. Thus, we could control the evolution of the disease status by reconfiguring particular setups of immune system to an innocuous target state.