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Reverse Engineering (Aracne)

Reverse Engineering (Aracne). Aracne. Aracne stands for “Algorithm for the Reconstruction of Accurate Cellular NEtworks”. Aracne uses information theory to compute the mutual information between pairs of markers (or genes) in a set of microarray experiments.

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Reverse Engineering (Aracne)

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  1. Reverse Engineering (Aracne)

  2. Aracne • Aracne stands for “Algorithm for the Reconstruction of Accurate Cellular NEtworks”. • Aracne uses information theory to compute the mutual information between pairs of markers (or genes) in a set of microarray experiments. • From these mutual information computations, an interaction network is inferred.

  3. Aracne C Implementation • Andrea’s group actively maintains a C implementation of Aracne. • Supports creating networks over all markers, a subset of markers, or a single hub marker. • This version is can also be used to do large, parallel runs for large data sets. • Manjunath is developing a Workbench component that calls this C implementation natively.

  4. Workbench Implementation • The Workbench implementation is called “Reverse Engineering”. It only supports running Aracne for a single hub gene. • It is run in two stages: compute interactions with the hub gene (Analyze 2D) and build the network (Create Network). • Cytoscape is used to display the networks created by Reverse Engineering.

  5. Issues - Correctness • The results do not match those of the C implementation. It has been confirmed with Andrea’s group that the Workbench version is incorrect. • Two of the interaction computation modes (Mutual Information – Fast, and Linear) are not functional. • Adjacency matrices cannot be loaded from the current version of the C Aracne implementation.

  6. Issues - Design • The words “gene” and “marker” are often confused in the interface. • The MYC gene is hard-coded in to the interface. • The Histograms do not lay out properly. • All sub-panels of Reverse Engineering except the first are probably not useful to anybody but Andrea’s team, but even they do not use Workbench for Aracne.

  7. Issues - Code • The codebase is enormous for the relatively limited amount of functionality. • There are many areas of redundancy. There seems to have been an attempt to rewrite parts of the algorithm, but both the old and new parts still exist and are now entangled. (For example, the CSInformationTheory class is approximately the same as GeneGeneRelationship). • Code documentation is fairly reasonable in some areas, but absent in others.

  8. Proposed Fixes • The existing interaction computation methods appear to be correct. This can be retained, but the network calculation code must be rewritten. • The interface is very poorly implemented, and it is not clear what most of it is for. A simpler and more convenient interface should be implemented from scratch. • Support for more than one hub gene should be included in the new implementation.

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