IntOGen & Gitools
integration, visualization and data-mining of
    multidimensional oncogenomic data

                Chr...
Outline
●   Introduction
●   Case study
●   Real projects
●   Conclusions
●   Future work
Outline
●   Introduction
●   Case study
●   Real projects
●   Conclusions
●   Future work
Gundem et al., Nature Methods 2010
Identification of cancer related genes




                                                                               ...
Identification of modules significantly altered in cancer
www.intogen.org
www.gitools.org
Data   Analysis   Browse   Export
Data   Analysis       Browse                    Export

                  Many File Formats Supported


                  ...
Data                     Analysis                          Browse                      Export

Import data from:   Marts

...
Data   Analysis   Browse   Export
Data   Analysis   Browse   Export
Data   Analysis   Browse   Export
Outline
●   Introduction
●   Case study
●   Real projects
●   Conclusions
●   Future work
Case study


●   What biological processes are enriched in genes
    significantly up-regulated in cancer ?

●   What is t...
Retrieving data for the analysis




                             • Biological Process
Importing data from IntOGen
Importing data from IntOGen
Importing data from IntOGen
Importing data from IntOGen
Importing data from IntOGen
Importing data from IntOGen
Importing data from IntOGen
Importing data from IntOGen
Importing modules from Ensembl
Importing modules from Ensembl
Importing modules from Ensembl
Importing modules from Ensembl
Importing modules from Ensembl
Importing modules from Ensembl
Importing modules from Ensembl
Importing modules from Ensembl
Enrichment analysis
                                                                                           Biological ...
Enrichment analysis
Enrichment analysis
Enrichment analysis
Enrichment analysis
Enrichment analysis
Enrichment analysis
Enrichment analysis
Enrichment analysis
Correlations
Correlations
Correlations
Correlations
Correlations
Outline
●   Introduction
●   Case study
●   Real projects
●   Conclusions
●   Future work
Real projects
●   RBP2 function
●   Functional protein divergence
●   Study of altered regulatory programs in cancer
●   S...
Real projects
●   RBP2 function
●   Functional protein divergence
●   Study of altered regulatory programs in cancer
●   S...
Outline
●   Introduction
●   Case study
●   Real projects
●   Conclusions
●   Future work
Conclusions
●   IntOGen is a novel framework for Oncogenomics data
    integration
●   IntOGen.org is a discovery tool for...
Future work
●   Biomart compatible interface for IntOGen
●   Implement more analysis:
    ●   GSEA
    ●   Clustering
    ...
Acknowledgements
  Nuria López-Bigas
   Gunes Gundem
   Jordi Deu-Pons
   Khademul Islam
  Michael Schroeder
   Alba Jené-...
IntOGen & Gitools
IntOGen & Gitools
IntOGen & Gitools
IntOGen & Gitools
IntOGen & Gitools
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IntOGen & Gitools

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There is an increasing amount of oncogenomic data available in the last years, and more is to come. The main challenges the scientific community is and will be facing are the integration of this data to extract new knowledge and the intuitive visualization of the results obtained in the analysis. Here two complementary but independent tools for the analysis of oncogenomic data are presented: IntOGen and GiTools.

IntOGen is a framework that includes public oncogenomic data and integrates it in different ways. Its main purpose is to identify those genes which are consistently altered (up or down-regulated) across many samples in a specific experiment, and combine all experiment from a same cancer type to end up having a p-value for a gene and cancer type. This same principle can then be applied to gene modules, or sets, which consist of groups of genes that share a biological property (module analysis). IntOGen has a web page from where the user can explore the datasets included in the database, from individual genes in all cancer types to different experiments, or gene modules (GO terms, KEGG pathways or user-defined groups of genes) across all the experiments.

GiTools is a desktop-based framework developed also by the lab which allows the analysis and visualization of genomic data. It supports different input formats (all plain text) and data can even be imported from BioMart, so everything stored in that database can be used directly in GiTools. Also there is an IntOGen data importer, so users can download matrices or oncomodules at different levels (experiments or combined results) and use them directly. Right now it can perform a limited number of analysis (enrichment analysis, correlations, results combination...) but it is built in a modular fashion and it can be easily expanded to include more matrix-based statistical tests. It allows the flexible exploration of the data and creating figures for papers from there directly, which can be exported in many different formats.

Two case studies are presented to illustrate the combined usefulness of these tools, aiming to answer two main questions: “what biological processes are enriched in genes siginificantly up-regulated in cancer?” and “what is the correlation between different tumour types for the pattern of genes up-regulated?”. Also different real applications of these tools are presented, both from published and unpublished research, stressing that they can be used not only in oncogenomics projects, but also in evolution and global gene regulation.

In the near future GiTools will be incorporating new analysis, such as GSEA and clustering, and connections with the R statistical framework. IntOGen will soon have a Biomart-compatible interface, which will make the data even more easily available.

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IntOGen & Gitools

  1. 1. IntOGen & Gitools integration, visualization and data-mining of multidimensional oncogenomic data Christian Pérez-Llamas Master student Biomedical Genomics GRIB-UPF April 2010
  2. 2. Outline ● Introduction ● Case study ● Real projects ● Conclusions ● Future work
  3. 3. Outline ● Introduction ● Case study ● Real projects ● Conclusions ● Future work
  4. 4. Gundem et al., Nature Methods 2010
  5. 5. Identification of cancer related genes Cancer type A exp. 1 exp. 2 exp. 3 exp. n experiment 1 samples STEP 1 STEP 2 identification of combination of genes driver alterations experiments + ... genes altered 0 0.05 1 not altered corrected p-value International Classification of Disease from Word Health Organization
  6. 6. Identification of modules significantly altered in cancer
  7. 7. www.intogen.org
  8. 8. www.gitools.org
  9. 9. Data Analysis Browse Export
  10. 10. Data Analysis Browse Export Many File Formats Supported TSV CDM BDM GMX GMT TCM
  11. 11. Data Analysis Browse Export Import data from: Marts ● International Cancer Genome Consorcium Data Levels Alterations ● Genes significantly altered ● Experiments ● Upregulation ● Modules of genes significantly altered ● Combinations ● Downregulation ● Gain ● Loss
  12. 12. Data Analysis Browse Export
  13. 13. Data Analysis Browse Export
  14. 14. Data Analysis Browse Export
  15. 15. Outline ● Introduction ● Case study ● Real projects ● Conclusions ● Future work
  16. 16. Case study ● What biological processes are enriched in genes significantly up-regulated in cancer ? ● What is the correlation between different tumour types for the pattern of genes up-regulated ?
  17. 17. Retrieving data for the analysis • Biological Process
  18. 18. Importing data from IntOGen
  19. 19. Importing data from IntOGen
  20. 20. Importing data from IntOGen
  21. 21. Importing data from IntOGen
  22. 22. Importing data from IntOGen
  23. 23. Importing data from IntOGen
  24. 24. Importing data from IntOGen
  25. 25. Importing data from IntOGen
  26. 26. Importing modules from Ensembl
  27. 27. Importing modules from Ensembl
  28. 28. Importing modules from Ensembl
  29. 29. Importing modules from Ensembl
  30. 30. Importing modules from Ensembl
  31. 31. Importing modules from Ensembl
  32. 32. Importing modules from Ensembl
  33. 33. Importing modules from Ensembl
  34. 34. Enrichment analysis Biological modules Tumor Tumor type i type i ... ... GO Biological processes Tumor type i ... STEP 1 STEP 2 genes genes Transform to 1 Enrichment p-values < 0.05 analysis modules Xi~Bin(pi) H0: pm = pi H1: pm > pi 0 0.05 1 Annotated genes p-value in module M
  35. 35. Enrichment analysis
  36. 36. Enrichment analysis
  37. 37. Enrichment analysis
  38. 38. Enrichment analysis
  39. 39. Enrichment analysis
  40. 40. Enrichment analysis
  41. 41. Enrichment analysis
  42. 42. Enrichment analysis
  43. 43. Correlations
  44. 44. Correlations
  45. 45. Correlations
  46. 46. Correlations
  47. 47. Correlations
  48. 48. Outline ● Introduction ● Case study ● Real projects ● Conclusions ● Future work
  49. 49. Real projects ● RBP2 function ● Functional protein divergence ● Study of altered regulatory programs in cancer ● Stress response genes and transition into increased malignant states ● Comparison of alteration patterns among tumor types RBP2 Functional Enrichment of RBP2 targets at different time points of differentiation Lopez-Bigas et al., Molecular Cell 2008
  50. 50. Real projects ● RBP2 function ● Functional protein divergence ● Study of altered regulatory programs in cancer ● Stress response genes and transition into increased malignant states ● Comparison of alteration patterns among tumor types Lopez-Bigas et al., Genome Biology 2008
  51. 51. Outline ● Introduction ● Case study ● Real projects ● Conclusions ● Future work
  52. 52. Conclusions ● IntOGen is a novel framework for Oncogenomics data integration ● IntOGen.org is a discovery tool for cancer researchers ● Gitools main features are: ● Interactive heatmap ● Import from Biomart ● Import from IntOGen ● Command line option
  53. 53. Future work ● Biomart compatible interface for IntOGen ● Implement more analysis: ● GSEA ● Clustering ● Modules hierarchy aware enrichment like Gostats ● Connection with R ● Implement more editors: ● Table and modules editor
  54. 54. Acknowledgements Nuria López-Bigas Gunes Gundem Jordi Deu-Pons Khademul Islam Michael Schroeder Alba Jené-Sanz Xavier Rafael Remember to visit www.intogen.org www.gitools.org
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