RT Journal Article
T1 GRaNIE and GRaNPA: inference and evaluation of enhancer‐mediated gene regulatory networks.
A1 Kamal, Aryan
A1 Arnold, Christian
A1 Claringbould, Annique
A1 Moussa, Rim
A1 Servaas, Nila H
A1 Kholmatov, Maksim
A1 Daga, Neha
A1 Nogina, Daria
A1 Mueller-Dott, Sophia
A1 Reyes-Palomares, Armando
A1 Palla, Giovanni
A1 Sigalova, Olga
A1 Bunina, Daria
A1 Pabst, Caroline
A1 Zaugg, Judith B
K1 Regulación genética
K1 Transcripción genética
K1 Macrófagos
AB Enhancers play a vital role in gene regulation and are critical in mediating the impact of noncoding genetic variants associated with complex traits. Enhancer activity is a cell‐type‐specific process regulated by transcription factors (TFs), epigenetic mechanisms and genetic variants. Despite the strong mechanistic link between TFs and enhancers, we currently lack a framework for jointly analysing them in cell‐type‐specific gene regulatory networks (GRN). Equally important, we lack an unbiased way of assessing the biological significance of inferred GRNs since no complete ground truth exists. To address these gaps, we present GRaNIE (Gene Regulatory Network Inference including Enhancers) and GRaNPA (Gene Regulatory Network Performance Analysis). GRaNIE (https://git.embl.de/grp‐zaugg/GRaNIE) builds enhancer‐mediated GRNs based on covariation of chromatin accessibility and RNA‐seq across samples (e.g. individuals), while GRaNPA (https://git.embl.de/grp‐zaugg/GRaNPA) assesses the performance of GRNs for predicting cell‐type‐specific differential expression. We demonstrate their power by investigating gene regulatory mechanisms underlying the response of macrophages to infection, cancer and common genetic traits including autoimmune diseases. Finally, our methods identify the TF PURA as a putative regulator of pro‐inflammatory macrophage polarisation.
PB Nature - EMBO
SN 1744-4292
YR 2023
FD 2023-04-19
LK https://hdl.handle.net/10630/41495
UL https://hdl.handle.net/10630/41495
LA eng
NO Kamal, A., Arnold, C., Claringbould, A. et al. GRaNIE and GRaNPA: inference and evaluation of enhancer‐mediated gene regulatory networks. Mol Syst Biol 19, MSB202311627 (2023). https://doi.org/10.15252/msb.202311627
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 19 ene 2026