Find Transcriptome Signatures with TranscriptomeBrowser

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Search public GEO datasets, identify specific transcriptome signatures, and perform functional enrichment on the found sets


TranscriptomeBrowser.png

Introduction

TranscriptomeBrowser (TBrowser)[1] host a large database of transcriptional signatures (TS) extracted from GEO public microarray repository [2]. TS have been produced using a new algorithm called "Density Based Filtering And Markov Clustering" (DBF-MCL). The current database contains about 30 000 TS derived from ~ 4 000 microarray datasets (~222 millions expression values). Each TS was tested for functional enrichment using annotation obtained from numerous ontologies or annotation databases (Gene Ontology, KEGG, BioCarta, Swiss-Prot, BBID, SMART, NIH Genetic Association DB, COG/KOG, TargetScan, PicTar, .TFBS_conserv.ed., MSigDB, GeneSigDB,...). TBrowser comes with a sophisticated search engine so that users can perform combined queries using boolean operators.

VERSION 3.0. TranscriptomeBrowser host a large database of transcriptional signatures (TS, n~40 000) extracted from Gene Expression Omnibus (~4 000 experiments) using the DBF-MCL algorithm. TBrowser comes with a sophisticated search engine so that users can search for the biological contexts in which several genes were concomitantly regulated. Several examples are provided below and in the article published in PLoSONE [1]. A video tutorial for TranscriptomeBrowser is available here and a second for the InteractomeBrowser plugin here. The full manual can be read here[3]

After installation (see online documentation) and startup, the main TBrowser interface awaits user input

TBrowser_main.png

A Walk-through example

As shown above, different search angles can be used to populate the interface. Instead of searching for genes, we choose to use here the GSE6943 dataset used in other BITS training tutorial(s). Please refer to the Hands-on_Analysis_of_public_microarray_datasets page for more information about this dataset.

Load the GSE6943 dataset

Change focus to search for 'Experiment' and type GSE6943 in the text field followed by a click on 'SEARCH'

01_search.png

Four enriched TS (Transcriptome Signatures) are found by the program

02_show_TS-results.png

Several options are available here (please explore) and we choose to show the results to get details about the four hits

03_select_all.png

Find Transcriptome Signatures

Selecting each of the four hits and displaying the detailed statistical results on the top-right window

  • first TS (662 genes) and Glycolysis as main aspect
04_view_1st-enriched.png
  • second TS (778 genes) related to mitochondrial functions
05_view_2nd-enriched.png
  • third TS (622) clearly associated with heart and mitochondrial functions
06_view_3rd-enriched.png
  • last TS (684) apparently specific to the cardiac muscle
07_view_4th-enriched.png

Show HeatMaps for each TS

For each TS, we can visualize the actual expression data as a heatmap by using the corresponding plugin

08_send-to-plugin.png
  • first heatmap (cut at ~20 genes)
09_show-heatmap1.png

the leftmost 6 samples are the Diaphragm replicates while the remaining ones are the Heart replicates

09b_samples.png

The full heatmap picture can be saved to file using buttons present at the bottom of the window

full heatmap#1

09c_TS1-heatmap.png

Similarly, text files can be saved with the data used to plot the heatmaps and a text table reporting enriched terms

  • second heatmap
10_show-heatmap2.png
  • third heatmap
11_show-heatmap3.png
  • fourth heatmap
11_show-heatmap3.png
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Other buttons and tabs allow inspecting details of any particular view. Genes can be sorted alpha or by clustering order and a given gene can be searched using the search box

Conclusion

And there is even more for Geeks

The data mining package, RTools4TB, can perform calls to TranscriptomeBrowser web service and implements the DBF-MCL algorithm. The R package RTools4TB is now part of the Bioconductor project.


References:
  1. 1.0 1.1 http://tagc.univ-mrs.fr/tbrowser/

    Cyrille Lepoivre, Aurélie Bergon, Fabrice Lopez, Narayanan B Perumal, Catherine Nguyen, Jean Imbert, Denis Puthier
    TranscriptomeBrowser 3.0: introducing a new compendium of molecular interactions and a new visualization tool for the study of gene regulatory networks.
    BMC Bioinformatics: 2012, 13;19
    [PubMed:22292669] ##WORLDCAT## [DOI] (I e)

    Fabrice Lopez, Julien Textoris, Aurélie Bergon, Gilles Didier, Elisabeth Remy, Samuel Granjeaud, Jean Imbert, Catherine Nguyen, Denis Puthier
    TranscriptomeBrowser: a powerful and flexible toolbox to explore productively the transcriptional landscape of the Gene Expression Omnibus database.
    PLoS One: 2008, 3(12);e4001
    [PubMed:19104654] ##WORLDCAT## [DOI] (I p)

  2. http://www.ncbi.nlm.nih.gov/gds/
  3. http://tagc.univ-mrs.fr/tbrowser/index2.php?option=com_content&task=view&id=19&pop=1&page=0&Itemid=23


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