Regulus infers signed regulatory relations from few samples' information using discretization and likelihood constraints - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue PLoS Computational Biology Année : 2024

Regulus infers signed regulatory relations from few samples' information using discretization and likelihood constraints

Résumé

Motivation Transcriptional regulation is performed by transcription factors (TF) binding to DNA in context-dependent regulatory regions and determines the activation or inhibition of gene expression. Current methods of transcriptional regulatory circuits inference, based on one or all of TF, regions and genes activity measurements require a large number of samples for ranking the candidate TF-gene regulation relations and rarely predict whether they are activations or inhibitions. We hypothesize that transcriptional regulatory circuits can be inferred from fewer samples by (1) fully integrating information on TF binding, gene expression and regulatory regions accessibility, (2) reducing data complexity and (3) using biology-based likelihood constraints to determine the global consistency between a candidate TF-gene relation and patterns of genes expressions and region activations, as well as qualify regulations as activations or inhibitions. Results We introduce Regulus, a method which computes TF-gene relations from gene expressions, regulatory region activities and TF binding sites data, together with the genomic locations of all entities. After aggregating gene expressions and region activities into patterns, data are integrated into a RDF (Resource Description Framework) endpoint. A dedicated SPARQL (SPARQL Protocol and RDF Query Language) query retrieves all potential relations between expressed TF and genes involving active regulatory regions. These TF-region-gene relations are then filtered using biological likelihood constraints allowing to qualify them as activation or inhibition. Regulus provides signed relations consistent with public databases and, when applied to biological data, identifies both known and potential new regulators. Regulus is devoted to context-specific transcriptional circuits inference in human settings where samples are scarce and cell populations are closely related, using discretization into patterns and likelihood reasoning to decipher the most robust regulatory relations.
Fichier principal
Vignette du fichier
journal.pcbi.1011816.pdf (2.64 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-04443527 , version 1 (07-02-2024)

Licence

Paternité

Identifiants

Citer

Marine Louarn, Guillaume Collet, Eve Barre, Thierry Fest, Olivier Dameron, et al.. Regulus infers signed regulatory relations from few samples' information using discretization and likelihood constraints. PLoS Computational Biology, 2024, 20 (1), pp.e1011816. ⟨10.1371/journal.pcbi.1011816⟩. ⟨hal-04443527⟩
44 Consultations
8 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More