one.step.pigengene {Pigengene} | R Documentation

## Runs the entire Pigengene pipeline

### Description

Runs the entire Pigengene pipeline, from gene expression to compact decision trees in a single function. It identifies the gene modules using coexpression network analysis, computes eigengenes, learns a Bayesian network, fits decision trees, and compact them.

### Usage

    one.step.pigengene(Data, saveDir = "Pigengene", Labels, testD = NULL,
      testLabels = NULL, doBalance = TRUE, RsquaredCut=0.8, costRatio = 1, toCompact = FALSE, bnNum = 0,
      bnArgs = NULL, useMod0 = FALSE, mit = "All", verbose = 0, doHeat = TRUE,
      seed = NULL, dOrderByW = TRUE, naTolerance=0.05)

### Arguments

`Data` | A matrix or data frame (or list of matrices or data frames) containing the training expression data, with genes corresponding to columns and rows corresponding to samples. Rows and columns must be named. For example, from RNA-Seq data, log(RPKM+1) can be used.
`Labels` | A (preferably named) vector containing the Labels (condition types) for the training Data. Or, if Data is a list, a list of label vectors corresponding to the data sets in Data. Names must agree with rows of `Data`.
`saveDir` | Directory to save the results.
`testD` | Test expression data with syntax similar to `Data`, possibly with different rows and columns.
`testLabels` | A (preferably named) vector containing the Labels (condition types) for the test Data.
`doBalance` | Boolean. Whether the data should be oversampled before identifying the modules so that each condition contribute roughly the same number of samples to clustering.
`RsquaredCut` | A threshold in the range [0,1] used to estimate the power. A higher value can increase power. For technical use only. See `pickSoftThreshold` for more details.
`costRatio` | A numeric value, the relative cost of misclassifying a sample from the first condition vs. misclassifying a sample from the second condition.
`toCompact` | An integer value determining which decision tree to shrink. It is the minimum number of genes per leaf imposed when fitting the tree. Set to `FALSE` to skip compacting, to `NULL` to automatically select the maximum value.
`bnNum` | Desired number of bootstraped Baysian networks. Set to `0` to skip BN learning.
`bnArgs` | A list of arguments passed to `learn.bn` function.
`useMod0` | Boolean, whether to allow module zero (the set of outliers) to be used as a predictor in the decision tree(s).
`mit` | The "module identification type", a character vector determining the reference conditions for clustering. If 'All' (default), clustering is performed using the entire data regardless of condition.
`verbose` | The integer level of verbosity. 0 means silent and higher values produce more details of computation.
`doHeat` | If `TRUE` the heatmap of expression of genes in the modules that contribute to the the tree will be plotted.
`seed` | Random seed to ensure reproducibility.
`dOrderByW` | If `TRUE`, the genes will be ordered in the csv file based on their absolute weight in the corresponding module.
`naTolerance` | Upper threshold on the fraction of entries per gene that can be missing. Genes with a larger fraction of missing entries are ignored. For genes with smaller fraction of NA entries, the missing values are imputed from their average expression in the other samples. See `check.pigengene.input`.

### Details

This is the main function of the package Pigengene and performs several steps: First, modules are identified in the training expression data, according to mit argument i.e. based on coexpression behaviour in the corresponding conditions. Set it to "All" to use all training data for this step regardless of the condition. Then, if a list of data frames is provided in Data, similarity networks on the data sets are computed and combined into one similarity network for the union of nodes across data sets. Then, the eigengenes for each module and each sample are calculated, where the expression of an eigengene of a module in a sample is the weighted average of the expression of the genes in that module in the sample. Technically, an eigengene is the first principal component of the gene expression in a module. PCA ensures that the maximum variance accross all the training samples is explained by the eigengene. Next, (optionally –if bnNum is set to a value greater than 0), several bootstrapped Bayesian networks are learned and combined into a consensus network, in order to detect and illustrate the probabilistic dependencies between the eigengenes and the disease subtype. Next, decisision tree(s) are built that use the module eigengenes, or a subset of them, to distinguish the classes (`Labels`). The accurracy of trees is assessed on the train and (if provided) test data. Finally, the number of required genes for the calculation of the relevant eigengenes is reduced (the tree is 'compacted'). The accuracy of the tree is reassessed after removal of each gene. Along the way, several self explanatory directories, heatmaps and plots are created and stored under `saveDir`.

### Value

A list with the following components:

`call` | The call that created the results.
`wgRes` | A list. The results of WGCNA clustering of the Data by `wgcna.one.step`.
`betaRes` | A list. The automatically selected beta (power) parameter which was used for the WGCNA clustering. It is the result of the call to `calculate.beta` using the expression data of `mit` conditions(s).
`pigengene` | The pigengene object computed for the clusters, result of `compute.pigengene`.
`leanrtBn` | A list. The results of `learn.bn` call for learning a Bayesian network using the eigengenes.
`selectedFeatures` | A vector of the names of module eigengenes that were considered during the construction of decision trees. If `bnNum` >0, this corresponds to the immediate neighbors of the Disease or Effect variable in the consensus network.
`c5treeRes` | A list. The results of `make.decision.tree` call for learning decision trees that use the eigengenes as features.

### Note

The individual functions are exported to facilitated running the pipeline step-by-step in a customized way.

### Author(s)

Amir Foroushani, Habil Zare, and Rupesh Agrahari

### References

Large-scale gene network analysis reveals the significance of extracellular matrix pathway and homeobox genes in acute myeloid leukemia, Foroushani A, Agrahari R, Docking R, Karsan A, and Zare H. In preparation.

### See Also

`check.pigengene.input`, `balance`, `calculate.beta`, `wgcna.one.step`, `compute.pigengene`, `learn.bn`, `make.decision.tree`, `blockwiseModules`

### Examples

    data(aml)
    data(mds)
    d1 <- rbind(aml,mds)
    Labels <- c(rep("AML",nrow(aml)),rep("MDS",nrow(mds)))
    names(Labels) <- rownames(d1)
    p1 <- one.step.pigengene(Data=d1,saveDir=".", bnNum=10, verbose=1, seed=1,
          Labels=Labels, toCompact=FALSE, doHeat=FALSE)
    plot(p1$c5treeRes$c5Trees[["34"]])

[Package Pigengene version 1.12.0 Index]