Using the Package

Get the source from Github and build the package:

# Install the dependencies, from R:
> install.packages(pkgs=c("WGCNA", "flashClust", "dynamicTreeCut"))
# now, from the command line, clone the Github repository
git clone https://github.com/Sage-Bionetworks/SageBionetworksCoex.git
# again, from the command line, build the package
R CMD INSTALL SageBionetworksCoex

In R, load the library:

> library(SageBionetworksCoex)

For guidance on using the package:

?SageBionetworksCoex

Table of Contents

Goals

1) Make the Sage coexpression software runnable by any data analyst in R.

Document the analysis steps, package functions, and adjustable parameters.  Write start-to-finish vignette(s) having sufficient detail to guide a new analyst through the software, including making parameter settings and other intermediate decisions.  Refactoring software to enhance readability and/or to make decision points and adjustable parameters explicit, is within scope for this goal.

2) Clearly explain the methodology underlying the coexpression algorithms.

This includes contrasting the Sage algorithms with the separately published “WGCNA” algorithms and explaining the rationale for the differences and the decision process for choosing which to use.

3) Make the Sage coexpression software publicly available.

The code must be available through a standard R distribution channel (CRAN or Bioconductor).  An option is to merge Sage-specific algorithms or steps into WGCNA (if the two are sufficiently overlapping).

4) Make the Sage coexpression software perform well, on commonly available hardware.

Currently, special high capacity hardware is required to run the Sage coexpression software on commonly encountered data set sizes.  The goal is to optimize the code to run on commonly available hardware, at a minimum the code should be runnable on the 68GB, quad core servers available through Amazon Web Services. Ideally, the code would be runnable on a “heavy” Sage laptop (8 GB total RAM).

Strategy

The steps for Sage Coexpression are: 

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heatmap generation for correlation and TOM matrices

Reduction of scale-free regression threshold (R^2) when no solution is found.

The Package

The source code for the created package is available on our Atlassian-hosted SVN repository, under the SCICOMP project:

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Intramodular statistics are faster, with identical results.
Diagnostic plot set is reduced from 12 to 86, omitting redundant plots.

Sample clustering was omitted, having been deemed unnecessary.

Additional Features

Option to do tree cutting and/or subsqeuent merging by UCLA-WGCNA algorithm or by 'Sage classic' algorithm.
Separation of rote, time consuming steps (correlation, TOM computation) from tree cutting.
Separation of analysis from plotting.
Separation of analysis from file system, to facilitate Synpase integration.

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Performance questions:  For datasets having >18,000 probes, how much time and space does each algorithm use?

 * These were run on an Amazon Elastic Compute Cloud (EC2) "High-Memory Quadruple Extra Large" unix server, having 68GB of RAM.

** Note:  UCLA-WGCNA package also runs out of memory.  (An alternative is to use the WGCNA preprocessing step of K-means decomposition, which has been shown to work with >50K genes.)

*** Run on Sage Bionetworks' "Belltown" Unix server, having 256GB RAM. 

**** http://florence.acadiau.ca/collab/hugh_public/index.php?title=R:compare_partitions
Note: We skip the performance evaluation for the small data sets.

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Goals, Revisited

Choices for package 'publication' include:

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