京都大学医学研究科統計遺伝学分野

主な内容
Bioconductor's page on ToPASeq

Vignette

Rcodes



Summary

Gene-expression data (Microarray, RNA-seq)

Topology-based pathway analysis methods (7 methods in one package)

Procedures

(1) Differential expression analysis

List genes differentially expressed between conditions
(2) Pathway analysis

Listed genes are mapped on pathways that were imported from databases somewhere
(3) Topological evaluation

Use topology of pathways to detect difference between conditions with better sensitivity/specificity performance
Seven methods implemented in ToPASeq -> See Table 1 inVignette
TopologyGSA
DEGraph
clipper
SPIA
TAPPA
PRS or TBS
PWEA
Miscelaneous

ToPASeq offers easy access to multiple methods
Visualization with Graphviz


Details

(1) Differential expression analysis

(i) Preparations (RNA-seq count normalization - TMM, DESeq)
(ii) Differential expression analysis (limma DESeq2)
Or you can do normalization/DE analysis yourself for downstream steps (SPIA,PRS,PWEA).
(2) Pathway analysis

Pathways are Graphs
Use graphite package to import pathways in KEGG, Biocarta, Reactome, NCI, SPIKE, HumanCyc,
G = (V,E)
Clique to handle protein complexes
Gene families are in the shape of parallels
Compound-mediated interaction (A-c-B => A-B)
If your own pathways, use utility functions in ToPASeq
(3) Topology analyses

(i) TopologyGSA

Gaussian Graphical Model on pathway graph with covariance matrix reflecting the pathway topology
Iterative Proportional Scaling for covariance matrix estimate
(ii) DEGraph

Assumes the same direction in the differential expression of genes in a pathway ("Discrete Signal Processing on Graphs")
(iii) clipper

Gaussian Graphical Model on pathway graph with covariance matrix reflecting the pathway topology
Shrinkage procedure of James-Stein-type for covariance matrix estimate
(iv) SPIA

Most well-known
Number of differentially expressed genes in pathway is considered
Pathway information is used as upstream genes in the pathway should be stronger and downstream weaker
Combine two information together to score pathways
(v) TAPPA

A bit classical
Handles genes as chemical atoms and a pathway as a chemical compound
(vi) PRS

Differentially expressed genes' effect should appear in downstream genes in pathway. This idea is used to summarize gene-wise significance.
(vii) PWEA

Pathway-information is used to expand GSEA.

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