Inference of an Integrative, Executable Network for Rheumatoid Arthritis Combining Data-Driven Machine Learning Approaches and a State-of-the-Art Mechanistic Disease Map - Inria - Institut national de recherche en sciences et technologies du numérique Access content directly
Journal Articles Journal of Personalized Medicine Year : 2021

Inference of an Integrative, Executable Network for Rheumatoid Arthritis Combining Data-Driven Machine Learning Approaches and a State-of-the-Art Mechanistic Disease Map

Abstract

Rheumatoid arthritis (RA) is a multifactorial, complex autoimmune disease that involves various genetic, environmental, and epigenetic factors. Systems biology approaches provide the means to study complex diseases by integrating different layers of biological information. Combining multiple data types can help compensate for missing or conflicting information and limit the possibility of false positives. In this work, we aim to unravel mechanisms governing the regulation of key transcription factors in RA and derive patient-specific models to gain more insights into the disease heterogeneity and the response to treatment. We first use publicly available transcriptomic datasets (peripheral blood) relative to RA and machine learning to create an RA-specific transcription factor (TF) co-regulatory network. The TF cooperativity network is subsequently enriched in signalling cascades and upstream regulators using a state-of-the-art, RA-specific molecular map. Then, the integrative network is used as a template to analyse patients’ data regarding their response to anti-TNF treatment and identify master regulators and upstream cascades affected by the treatment. Finally, we use the Boolean formalism to simulate in silico subparts of the integrated network and identify combinations and conditions that can switch on or off the identified TFs, mimicking the effects of single and combined perturbations.
Fichier principal
Vignette du fichier
jpm-11-00785-v2.pdf (5.2 Mo) Télécharger le fichier
Origin Publisher files allowed on an open archive

Dates and versions

hal-03515663 , version 1 (06-01-2022)

Identifiers

Cite

Quentin Miagoux, Vidisha Singh, Dereck de Mézquita, Valérie Chaudru, Mohamed Elati, et al.. Inference of an Integrative, Executable Network for Rheumatoid Arthritis Combining Data-Driven Machine Learning Approaches and a State-of-the-Art Mechanistic Disease Map. Journal of Personalized Medicine, 2021, 11 (8), pp.785. ⟨10.3390/jpm11080785⟩. ⟨hal-03515663⟩
118 View
49 Download

Altmetric

Share

Gmail Mastodon Facebook X LinkedIn More