The IntegrativePathwayAnalysis class — IntegrativePathwayAnalysis-class • MIRit

This class stores the output of integrative multi-omic pathway analyses. In particular, the slots of this class are suitable to represent the results of topologically-aware integrative pathway analysis (TAIPA) returned from the topologicalAnalysis() function.

Usage

# S4 method for class 'IntegrativePathwayAnalysis'
integratedPathways(object)

# S4 method for class 'IntegrativePathwayAnalysis'
integrationDatabase(object)

# S4 method for class 'IntegrativePathwayAnalysis'
augmentedPathways(object)

# S4 method for class 'IntegrativePathwayAnalysis'
show(object)

Arguments

object: An object of class IntegrativePathwayAnalysis containing the results of a miRNA-mRNA pathway analysis

Value

the integratedPathways() function returns a data.frame with the results of the integrative pathway analysis.

the integrationDatabase() function returns a character object with the database used for the analysis.

the augmentedPathways() function returns a list object containing the miRNA-augmented pathways considered for TAIPA.

Details

Analysis results

The data slot of this class consists in a data.frame object with six columns, namely:

pathway, which indicates the name of the biological network;
coverage, which specifies the fraction of nodes with expression measurement available;
score, which expresses the score of each individual pathway;
normalized.score, which indicates the pathway scores after standardizing the values for the null distribution computed through permutations;
P.Val, the resulting p-value of each pathway;
adj.P.Val, the p-value adjusted for multiple testing.

Organisms and databases

The organism and database slots specify the organism in study and the database used for retrieving biological interactions, respectively. In particular, the topologicalAnalysis() function supports KEGG, WikiPathways, and Reactome databases. Regarding organisms, the supportedOrganisms() function can be used to retrieve the available species for each database.

Statistical significance of the permutation test

pCutoff and pAdjustment slots refer to the cutoff used for the analysis. pCutoff is the threshold used for defining statistically significant pathways, whereas pAdjustment refers to the multiple testing correction method used.

Furthermore, since the statistical significance of each pathway is defined on the basis of a permutation test, the number of permutations is also specified in the nPerm slot.

Augmented pathways

The pathways slot contains a list with weighted graph objects, each representing a biological pathway. These networks have been enlarged by adding the observed miRNA-mRNA interactions. Each network has been processed so that the weight of each edge is +1 for activation interactions, and -1 for repression interactions, such as those occurring between miRNAs and mRNAs.

Differential expression results for both miRNAs and genes

The expression variation of all miRNAs and genes measured in the study is stored in the expression slot. In particular, this slot consists of a data.frame object with different information, including log2 fold changes, node weights and p-values.

Minimum percentage of measured features

The minPc slot indicates the minimum percentage of miRNAs/mRNAs above which pathways have been considered for the integrative analysis. This is needed because often, when differential expression analysis is performed, lowly expressed features are removed. Therefore, some pathways might result significantly affected even if only 1% of nodes is perturbed.

Functions

integratedPathways(IntegrativePathwayAnalysis): Access the results of integrative miRNA-mRNA pathway analysis
integrationDatabase(IntegrativePathwayAnalysis): View the database used for the integrative pathway analysis
augmentedPathways(IntegrativePathwayAnalysis): Extract the list of biological networks augmented with miRNA-mRNA interactions
show(IntegrativePathwayAnalysis): Show method for objects of class IntegrativePathwayAnalysis

Slots

data: A data.frame object that contains the results of the integrative pathway analysis. See the details section for further details
method: The method used for the analysis
organism: The name of the organism under consideration (e.g. Homo sapiens)
database: The name of the database used for retrieving biological pathways (e.g. KEGG)
pCutoff: A numeric value defining the threshold used for statistical significance (e.g. 0.05)
pAdjustment: A character indicating the method used to correct p-values for multiple testing (e.g. fdr)
pathways: A list of graph objects containing the biological networks retrieved from database, and augmented with miRNA-mRNA interactions
expression: A data.frame object containing differential expression results for both miRNAs and genes
minPc: The minimum percentage of measured features that a pathway must have for being considered in the analysis
nPerm: The number of permutation used for assessing the statistical significance of each pathway

Author

Jacopo Ronchi, jacopo.ronchi@unimib.it