GRaNIE

GRaNIE reconstructs cell type-specific gene regulatory networks including enhancers using single-cell or bulk chromatin accessibility and RNA-seq data.

Key Features:

• Multi-omics integration: Integrates single-cell or bulk RNA-seq with open chromatin data from ATAC-seq, ChIP-seq for open chromatin marks, and optionally (Capture) Hi-C data.
• TF activity quantification: Incorporates transcription factor activity differences in open chromatin regions using tools such as diffTF.
• Network link types: Constructs networks with TF-to-regulatory element links and regulatory element-to-gene links, connecting genes in the vicinity or within the same topologically associating domain.
• Statistical significance: Assigns empirical false discovery rates and weights to all links using a permutation-based approach.

Scientific Applications:

• Non-coding variant interpretation: Identifies genes modulated by specific regulatory elements to understand the effects of disease-associated genetic variants in non-coding regions.
• Cell-type-specific regulation: Captures cell-type and data-specific transcription factor-regulatory element and regulatory element-gene links.

Methodology:

GRaNIE uses a statistical framework with a permutation-based approach to assign empirical FDRs and weights to all network links.