Abstract
BackgroundConnectivity mapping is a process to recognize novel pharmacological and toxicological properties in small molecules by comparing their gene expression signatures with others in a database. A simple and robust method for connectivity mapping with increased specificity and sensitivity was recently developed, and its utility demonstrated using experimentally derived gene signatures.ResultsThis paper introduces sscMap (statistically significant connections' map), a Java application designed to undertake connectivity mapping tasks using the recently published method. The software is bundled with a default collection of reference gene-expression profiles based on the publicly available dataset from the Broad Institute Connectivity Map 02, which includes data from over 7000 Affymetrix microarrays, for over 1000 small-molecule compounds, and 6100 treatment instances in 5 human cell lines. In addition, the application allows users to add their custom collections of reference profiles and is applicable to a wide range of other 'omics technologies.ConclusionThe utility of sscMap is two fold. First, it serves to make statistically significant connections between a user-supplied gene signature and the 6100 core reference profiles based on the Broad Institute expanded dataset. Second, it allows users to apply the same improved method to custom-built reference profiles which can be added to the database for future referencing. The software can be freely downloaded from .
Highlights
Connectivity mapping is a process to recognize novel pharmacological and toxicological properties in small molecules by comparing their gene expression signatures with others in a database
The primary utility of sscMap is for users who want to compare their gene signatures to the reference profiles based on the Connectivity Map 02 dataset
The sscMap program can be run in two execution modes: as a command line program, or as a GUI (Graphical User Interface) application
Summary
The core database The Broad Institute released Build 02 of their Connectivity Map http://www.broad.mit.edu/cmap/ with an expanded dataset over the 01 version with more compounds utilized Using these data we constructed 6100 reference gene-expression profiles using the method described in our previous report [2]. In the simple command line mode using the built-in core database users can put their gene signature files into the queries folder and run the application. Flexibility: Treatment set definition The sscMap software downloads with a default ref-files folder containing 6100 pre-built reference expression profiles. Example 2: Using a custom collection of ref-files In the folder custom-example we provided a small collection of 18 custom reference profiles, constructed using Affymetrix RAT230_2 microarray data We queried this small database of custom reference profiles using 2 specially prepared gene signatures based on mouse cDNA microarray data.
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