PiER

PiER prioritizes genetic targets by integrating human disease genetics, functional genomics, protein interaction networks, and pathway-derived interactions to support translational target discovery and drug repurposing.

Key Features:

• eV2CG: Uses functional genomics to connect disease-associated variants, including non-coding variants, to core genes likely responsible for genetic associations.
• eCG2PG: Uses protein interaction data to network core genes with peripheral genes and generates ranked lists of core and peripheral genes based on interactions.
• eCrosstalk: Exploits pathway-derived interactions to identify highly ranked genes that mediate crosstalk between molecular pathways.
• cTGene: Automates integration of genetics-led and network-based prioritization to produce prioritized core target genes.
• cTCrosstalk: Automates identification and prioritization of targets involved in pathway crosstalk.
• Sequential integration: Sequentially connects variant-to-gene mapping, network expansion, and pathway crosstalk analyses to generate ranked target prioritizations.

Scientific Applications:

• Translational target discovery: Translates human disease genetics into prioritized targets for early-stage drug discovery.
• Drug repurposing: Identifies candidate repurposing targets by mapping disease-associated variants to networked and ranked genes.
• Mechanistic insight: Reveals genes mediating pathway crosstalk to elucidate disease mechanisms.
• Therapeutic nomination: Ranks core and peripheral genes to inform selection of therapeutic targets.

Methodology:

Applies functional genomics to link non-coding variants with core genes, employs protein interaction networks to rank and identify relevant gene interactions, and uses pathway analysis to detect crosstalk between molecular pathways.