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|
|Bioconductor views||GeneExpression GeneTarget Genetics GenomeWideAssociation GraphAndNetwork HiC LinkageDisequilibrium Network Pathways Software|
|Date of publication||None|
|Maintainer||Hai Fang <firstname.lastname@example.org>|
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 features used for machine learning
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...
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