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

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).

AuthorHai Fang, the ULTRA-DD Consortium, Julian C Knight
Bioconductor views GeneExpression GeneTarget Genetics GenomeWideAssociation GraphAndNetwork HiC LinkageDisequilibrium Network Pathways Software
Date of publication2017-04-21 15:19:29
MaintainerHai Fang <hfang@well.ox.ac.uk>
LicenseGPL-3
Version1.3.4
http://pi314.r-forge.r-project.org

View on R-Forge

Man pages

cTarget: Definition for S3 class 'cTarget'

dTarget: Definition for S3 class 'dTarget'

eGSEA: Definition for S3 class 'eGSEA'

eTarget: Definition for S3 class 'eTarget'

pNode: Definition for S3 class 'pNode'

pPerf: Definition for S3 class 'pPerf'

sGS: Definition for S3 class 'sGS'

sTarget: Definition for S3 class 'sTarget'

xContour: Function to visualise a numeric matrix as a contour plot

xGSEAbarplot: Function to visualise GSEA results using a barplot

xGSEAconciser: Function to make GSEA results conciser by removing redundant...

xGSEAdotplot: Function to visualise GSEA results using dot plot

xGSsimulator: Function to simulate gold standard negatives (GSN) given gold...

xMLcaret: Function to integrate predictor matrix in a supervised manner...

xMLcompare: Function to visualise cross-validation performance against...

xMLdensity: Function to visualise machine learning results using density...

xMLdotplot: Function to visualise machine learning results using dot plot

xMLfeatureplot: Function to visualise/assess features used for machine...

xMLglmnet: Function to integrate predictor matrix in a supervised manner...

xMLparameters: Function to visualise cross-validation performance against...

xMLrandomforest: Function to integrate predictor matrix in a supervised manner...

xMLzoom: Function to visualise machine learning results using zoom...

xPCHiCplot: Function to visualise promoter capture HiC data using...

xPier: Function to do prioritisation through random walk techniques

xPierAnno: Function to prioritise seed genes only from a list of pNode...

xPierCross: Function to extract priority matrix from a list of...

xPierEvidence: Function to extract evidence from a list of pNode objects

xPierGenes: Function to prioritise genes from an input network and the...

xPierGSEA: Function to prioritise pathways based on GSEA analysis of...

xPierManhattan: Function to visualise prioritised genes using manhattan plot

xPierMatrix: Function to extract priority or evidence matrix from a list...

xPierPathways: Function to prioritise pathways based on enrichment analysis...

xPierROCR: Function to assess the dTarget performance via ROC and...

xPierSNPs: Function to prioritise genes given a list of seed SNPs...

xPierSNPsAdv: Function to prepare genetic predictors given a list of seed...

xPierSNPsConsensus: Function to resolve relative importance of distance weight...

xPierSubnet: Function to identify a gene network from top prioritised...

xPierTrack: Function to visualise a prioritised gene using track plot

xPierTrackAdv: Function to visualise a list of prioritised genes using...

xPredictCompare: Function to compare prediction performance results

xPredictROCR: Function to assess the prediction performance via ROC and...

xRWR: Function to implement Random Walk with Restart (RWR) on the...

xSNP2cGenes: Function to define HiC genes given a list of SNPs

xSNP2eGenes: Function to define eQTL genes given a list of SNPs or a...

xSNPeqtl: Function to extract eQTL-gene pairs given a list of SNPs or a...

xSNPhic: Function to extract promoter capture HiC-gene pairs given a...

xVisEvidence: Function to visualise evidence for prioritised genes in a...

Functions

cTarget Man page
dTarget Man page
eGSEA Man page
eTarget Man page
pNode Man page
pPerf Man page
print.cTarget Man page
print.dTarget Man page
print.eGSEA Man page
print.eTarget Man page
print.pNode Man page
print.pPerf Man page
print.sGS Man page
print.sTarget Man page
sGS Man page
sTarget Man page
xContour Man page
xGSEAbarplot Man page
xGSEAconciser Man page
xGSEAdotplot Man page
xGSsimulator Man page
xMLcaret Man page
xMLcompare Man page
xMLdensity Man page
xMLdotplot Man page
xMLfeatureplot Man page
xMLglmnet Man page
xMLparameters Man page
xMLrandomforest Man page
xMLzoom Man page
xPCHiCplot Man page
xPier Man page
xPierAnno Man page
xPierCross Man page
xPierEvidence Man page
xPierGenes Man page
xPierGSEA Man page
xPierManhattan Man page
xPierMatrix Man page
xPierPathways Man page
xPierROCR Man page
xPierSNPs Man page
xPierSNPsAdv Man page
xPierSNPsConsensus Man page
xPierSubnet Man page
xPierTrack Man page
xPierTrackAdv Man page
xPredictCompare Man page
xPredictROCR Man page
xRWR Man page
xSNP2cGenes Man page
xSNP2eGenes Man page
xSNPeqtl Man page
xSNPhic Man page
xVisEvidence Man page

Files

DESCRIPTION
NAMESPACE
R
R/ClassMethod-Pi.r R/xContour.r R/xGSEAbarplot.r R/xGSEAconciser.r R/xGSEAdotplot.r R/xGSsimulator.r R/xMLcaret.r R/xMLcompare.r R/xMLdensity.r R/xMLdotplot.r R/xMLfeatureplot.r R/xMLglmnet.r R/xMLparameters.r R/xMLrandomforest.r R/xMLzoom.r R/xPCHiCplot.r R/xPier.r R/xPierAnno.r R/xPierCross.r R/xPierEvidence.r R/xPierGSEA.r R/xPierGenes.r R/xPierManhattan.r R/xPierMatrix.r R/xPierPathways.r R/xPierROCR.r R/xPierSNPs.r R/xPierSNPsAdv.r R/xPierSNPsConsensus.r R/xPierSubnet.r R/xPierTrack.r R/xPierTrackAdv.r R/xPredictCompare.r R/xPredictROCR.r R/xRWR.r R/xSNP2cGenes.r R/xSNP2eGenes.r R/xSNPeqtl.r R/xSNPhic.r R/xVisEvidence.r
build
build/vignette.rds
inst
inst/CITATION
inst/NEWS
inst/Pi.icon.png
inst/Pi.logo.png
inst/cTarget.html
inst/dTarget.html
inst/doc
inst/doc/Pi_vignettes.Rmd
inst/doc/Pi_vignettes.html
inst/eGSEA.html
inst/eTarget.html
inst/pNode.html
inst/pPerf.html
inst/sGS.html
inst/sTarget.html
inst/xContour.html
inst/xGSEAbarplot.html
inst/xGSEAconciser.html
inst/xGSEAdotplot.html
inst/xGSsimulator.html
inst/xMLcaret.html
inst/xMLcompare.html
inst/xMLdensity.html
inst/xMLdotplot.html
inst/xMLfeatureplot.html
inst/xMLglmnet.html
inst/xMLparameters.html
inst/xMLplot.html
inst/xMLrandomforest.html
inst/xMLzoom.html
inst/xPCHiCplot.html
inst/xPier.html
inst/xPierAnno.html
inst/xPierCross.html
inst/xPierEvidence.html
inst/xPierGSEA.html
inst/xPierGenes.html
inst/xPierManhattan.html
inst/xPierMatrix.html
inst/xPierPathways.html
inst/xPierROCR.html
inst/xPierSNPs.html
inst/xPierSNPsAdv.html
inst/xPierSNPsConsensus.html
inst/xPierSubnet.html
inst/xPierTrack.html
inst/xPierTrackAdv.html
inst/xPredictCompare.html
inst/xPredictPR.html
inst/xPredictROCR.html
inst/xRWR.html
inst/xSNP2cGenes.html
inst/xSNP2eGenes.html
inst/xSNPeqtl.html
inst/xSNPhic.html
inst/xVisEvidence.html
man
man/cTarget.Rd man/dTarget.Rd man/eGSEA.Rd man/eTarget.Rd man/pNode.Rd man/pPerf.Rd man/sGS.Rd man/sTarget.Rd man/xContour.Rd man/xGSEAbarplot.Rd man/xGSEAconciser.Rd man/xGSEAdotplot.Rd man/xGSsimulator.Rd man/xMLcaret.Rd man/xMLcompare.Rd man/xMLdensity.Rd man/xMLdotplot.Rd man/xMLfeatureplot.Rd man/xMLglmnet.Rd man/xMLparameters.Rd man/xMLrandomforest.Rd man/xMLzoom.Rd man/xPCHiCplot.Rd man/xPier.Rd man/xPierAnno.Rd man/xPierCross.Rd man/xPierEvidence.Rd man/xPierGSEA.Rd man/xPierGenes.Rd man/xPierManhattan.Rd man/xPierMatrix.Rd man/xPierPathways.Rd man/xPierROCR.Rd man/xPierSNPs.Rd man/xPierSNPsAdv.Rd man/xPierSNPsConsensus.Rd man/xPierSubnet.Rd man/xPierTrack.Rd man/xPierTrackAdv.Rd man/xPredictCompare.Rd man/xPredictROCR.Rd man/xRWR.Rd man/xSNP2cGenes.Rd man/xSNP2eGenes.Rd man/xSNPeqtl.Rd man/xSNPhic.Rd man/xVisEvidence.Rd
vignettes
vignettes/Pi_vignettes.Rmd
vignettes/now.Pi.bib
vignettes/saved.Pi.functions.old.png
vignettes/saved.Pi.functions.png
vignettes/saved.Pi.gene_manhattan.png
vignettes/saved.Pi.network_vis.png
vignettes/saved.Pi.pathway_barplot.png
vignettes/saved.Pi.workflow.old.png
vignettes/saved.Pi.workflow.png
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