Pi

This package is for version 3.9 of Bioconductor; for the stable, up-to-date release version, see Pi.

Leveraging Genetic Evidence to Prioritise Drug Targets at the Gene and Pathway Level


Bioconductor version: 3.9

Priority index or Pi is developed as a genomic-led target prioritisation system, with the focus on leveraging human genetic data to prioritise potential drug targets at the gene, pathway and network level. The long term goal is to use such information to enhance early-stage target validation. Based on evidence of disease association from genome-wide association studies (GWAS), this prioritisation system is able to generate evidence to support identification of the specific modulated genes (seed genes) that are responsible for the genetic association signal by utilising knowledge of linkage disequilibrium (co-inherited genetic variants), distance of associated variants from the gene, evidence of independent genetic association with gene expression in disease-relevant tissues, cell types and states, and evidence of physical interactions between disease-associated genetic variants and gene promoters based on genome-wide capture HiC-generated promoter interactomes in primary blood cell types. Seed genes are scored in an integrative way, quantifying the genetic influence. Scored seed genes are subsequently used as baits to rank seed genes plus additional (non-seed) genes; this is achieved by iteratively exploring the global connectivity of a gene interaction network. Genes with the highest priority are further used to identify/prioritise pathways that are significantly enriched with highly prioritised genes. Prioritised genes are also used to identify a gene network interconnecting highly prioritised genes and a minimal number of less prioritised genes (which act as linkers bringing together highly prioritised genes).

Author: Hai Fang, the ULTRA-DD Consortium, Julian C Knight

Maintainer: Hai Fang <hfang at well.ox.ac.uk>

Citation (from within R, enter citation("Pi")):

Installation

To install this package, start R (version "3.6") and enter:


if (!require("BiocManager", quietly = TRUE))
    install.packages("BiocManager")

BiocManager::install("Pi")

For older versions of R, please refer to the appropriate Bioconductor release.

Documentation

To view documentation for the version of this package installed in your system, start R and enter:

browseVignettes("Pi")
Pi User Manual (R/Bioconductor package) HTML R Script
Reference Manual PDF
NEWS Text

Details

biocViews GeneExpression, GeneTarget, Genetics, GenomeWideAssociation, GraphAndNetwork, HiC, LinkageDisequilibrium, Network, Pathways, Software
Version 1.12.0
In Bioconductor since BioC 3.4 (R-3.3) (7.5 years)
License GPL-3
Depends XGR, igraph, dnet, ggplot2, graphics
Imports Matrix, ggbio, GenomicRanges, GenomeInfoDb, supraHex, scales, grDevices, ggrepel, ROCR, randomForest, glmnet, Gviz, lattice, caret, plot3D, stats
System Requirements
URL http://pi314.r-forge.r-project.org
Bug Reports https://github.com/hfang-bristol/Pi/issues
See More
Suggests foreach, doParallel, BiocStyle, knitr, rmarkdown, png, GGally, gridExtra, ExpressionAtlas, ggforce, fgsea, pathview, tidyr, dplyr
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Depends On Me
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Package Archives

Follow Installation instructions to use this package in your R session.

Source Package Pi_1.12.0.tar.gz
Windows Binary Pi_1.12.0.zip
Mac OS X 10.11 (El Capitan) Pi_1.12.0.tgz
Source Repository git clone https://git.bioconductor.org/packages/Pi
Source Repository (Developer Access) git clone git@git.bioconductor.org:packages/Pi
Bioc Package Browser https://code.bioconductor.org/browse/Pi/
Package Short Url https://bioconductor.org/packages/Pi/
Package Downloads Report Download Stats
Old Source Packages for BioC 3.9 Source Archive