Cancer Gene Prioritization

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    Cancer Gene Prioritization - Presentation Transcript

    1. TUTORIAL - CANCER GENE PRIORITIZATION Prioritize a list of candidate genes based on CGPrio probabilities and oncogenomic alterations
    2. STEP 1 Go to www.intogen.org & Click on Browser
    3. STEP 2 Click on Upload filter
    4. STEP 3 Select the type of gene IDs for the list that you are providing NOTE STEP 4 For this tutorial we are going to load a list of 37 candidate Paste the list of genes to cancer genes identified after a prioritize. mutation screening of 20661 You can also upload a human genes in 22 human file with the list of genes. tumor samples of Glioblastoma multiforme. (Parson et al Science 2008) STEP 5 Click on Create filter
    5. STEP 6 Select the type of cancer in which you are interested. In this case we will select brain tumors since we are studying a list of candidate cancer genes for glioblastoma. These values are based on predictions by CGPrio method. Genes with higher probability rank are more likely to be involved in cancer. The CGPrio method is based on computational classifiers that use different combinations of sequence This indicates that the filter and functional data including is applied. You can click sequence conservation, protein cross sign to eliminate the domains and interactions, and filter and see all genes, regulatory data. instead of only selected ones For more information see Furney et al., NAR 2008 This table informs if the With this links you can gene is in the Cancer Gene go to the next page to Census of the Sanger see the rest of genes. Center and which type of In total there are 37. mutations are known in cancer samples.
    6. Note that now we are on the page for brain and related tumor types This table gives a summary of known alterations of each gene in the tumor type selected These colors indicate significance. Color toward red means that this gene is significantly altered in this tumor type Color scale of corrected p-values: Gray = no significantly altered Reddish = significantly altered Gray means that this gene White means that there is no data for is not significantly altered this gene in this (CNA gain in this case) in tumor type this tumor type
    7. STEP 7 STEP 5 You can sort the table by clicking to the title of any column, to have the genes with lowest or highest values in the top. Click Onco twice to sort by those genes more likely to be involved in cancer (as oncogenes) This column gives information on mutations found and analyzed in these genes in this tumor type. This information comes from COSMIC
    8. STEP 8 You can sort the table by Now in the top of the table clicking to the title of any we have the genes that are column, to have the genes more significantly up- more significantly altered in regulated in brain and related the top. Click Up to sort by tumors up-regulation STEP 9 For any of the genes you can get detailed information. For example click on EGFR gene Note that you can get the data in excel by clicking on ‘CSV file’ under ‘Export”
    9. Note that now we are on the page for EGFR for brain and related tumor types STEP 10 Click on Tumor types Tab This box shows details of mutations of EGFR in brain cancer. The number of samples with mutations (41) and the number of samples analyzed (879). And the link to COSMIC for this gene. This box shows details of prediction ranks for EGFR This box shows some gene obtained with CGPrio gene details and link to for the different sets of ensembl properties analyzed. This box indicate that this gene is in the Cancer Gene Census, and it give details about the type of mutations identified.
    10. STEP 11 Now click on Experiments Tab to see details This Table gives information on the alterations found in EGFR in different morphology types for brain cancer. Note that this gene is amplified and up- regulated in almost all brain morphology types studied.
    11. This is the list of experiments that have analyzed EGFR in brain cancer and related tissues. White cells means no data. In this case means that this experiment has not analyzed transcriptomic alterations STEP 12 Click on this experiment to see the details This color shows thie region of this gene is gained in a significant N = number number of samples of of samples the 70 analyzed analyzed
    12. STEP 12 Click Up to have the experiments in which this gene is significantly up-regulated in the top STEP 13 Click on this experiment to see the details
    13. Note that now we are on the page of EGFR for a particular experiment of brain cancer This box gives details This box gives details of up- of the experiment, regulation of EGFR in this including authors, title experiment. 244 samples have and link to the been analyzed, of which of which publication or original 104 show over-expression of this source of data gene. The expected number of samples with alteration by chance is about 4. The over-expression is highly significant
    14. STEP 13 Click all in Experiments and all in Tumor type to see the information of known cancer alterations in EGFR in other tumor types
    15. Note that now we on the page for EGFR for all tumor types STEP 14 Click all in Genes to go back to the complete genes of genes This table gives information of known cancer alterations in different tumor types found in EGFR gene. In this case we can see that the region of this gene is significantly amplified (gained) in several tumor types, it is transcriptionally altered in some and a number of mutations have been found in different tumor types.
    16. Now we see the page showing all the tumor types for all genes included in the filter and all tumor types The filter is still applied, so we can continue navigating over the evidences for involvement in cancer of our group of genes of interest
    17. THANKS FOR USING INTOGEN You will find more tutorials and documentation in www.intogen.org

    + Biomedical Genomics (GRIB)Biomedical Genomics (GRIB), 6 months ago

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