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Cancer Gene Prioritization

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Cancer Gene Prioritization

  1. 1. TUTORIAL - CANCER GENE PRIORITIZATION Prioritize a list of candidate genes based on CGPrio probabilities and oncogenomic alterations
  2. 2. STEP 1Go to www.intogen.org& Click Browser
  3. 3. STEP 2Click on Upload filter.
  4. 4. STEP 3 Select the type of gene IDs for the list that you are providing STEP 4 Paste the list of genes to prioritize. NOTE You can also upload a For this tutorial we are file with the list of going to load a list of 37 genes. candidate cancer genes identified after a mutation screening of 20661 human genes in 22 human tumor samples of Glioblastoma STEP 5 multiforme.Click on Create filter (Parson et al Science 2008)
  5. 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 a higher probability rank are more likely to be involved in cancer. The CGPrio method is based onThis indicates that the computational classifiers thatfilter is applied. You can use different combinations ofclick the red x to sequence and functional dataeliminate the filter and including sequencereturn to the list of all conservation, protein domainsgenes. and interactions, and regulatory data. For more information see Furney et al., NAR 2008 This table informs if the gene is in the Cancer Gene Census of the With these links you Sanger Center and can go to the next which type of mutations page to see the rest are annotated there. of genes. In total there are 37.
  6. 6. Note that now we are on the page for brain and related tumor types This table gives a summary of alterations found for each gene in the selected tumor type. The 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 alteredRed/Yellow = significantly altered Gray means that this White means that gene is not significantly there is no data altered (CNA gain in this for this gene in case) in this tumor type this tumor type
  7. 7. STEP 7 STEP 5You can sort the table by clicking thetitle of any column, to have the geneswith lowest or highest values on top.Click Onco twice to sort by those geneswith the highest oncogene predictionrank. This column gives information on mutations in these genes found and studied in this tumor type. This information is imported from COSMIC.
  8. 8. STEP 8 Now in the top of the table You can sort the table by we have the genes that clicking to the title of any are more significantly up- column, to have the genes regulated in brain and more significantly altered in related tumors the top. Click Up to sort by up-regulation. STEP 9 For any of the genes you can get detailed information. For example click on the Ensembl ID for EGFR .Note that you canretrieve the data ina tabulated file byclicking on ‘CSV file’under ‘Export.
  9. 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 ofmutations of EGFR in brain cancer.The number of samples withmutations (103), the number ofsamples analyzed (1643) and thelink to COSMIC for this gene. This box shows details of prediction ranks for EGFR gene obtained This box shows with CGPrio for the some gene details different sets of This box indicate that this gene and link to ensembl properties analyzed. is in the Cancer Gene Census, and it give details about the type of mutations identified.
  10. 10. STEP 11 Now click on Experiments Tab to see detailsThis table gives information on thealterations found in EGFR indifferent morphologies of braincancer. Note that this gene isamplified and up-regulated inmany morphologies.
  11. 11. This is the list of experiments that have analyzed EGFR in brain cancer and related tissues.The color indicates N = numberthat the region of of samplesthis gene is analyzedamplified in asignificant number ofthe 171 samplesanalyzed. White cells means no data. In this case, it means that this experiment has not analyzed transcriptomic alterations
  12. 12. STEP 12 Click Up to have the experiments on top in which this gene is significantly up- regulated. STEP 13Click on theexperiment by Sun Let al to see thedetails.
  13. 13. Note that now we are on the page of EGFR for a particular experiment of brain cancer.This box givesdetails of theexperiment,including authors,title and link to thepublication ororiginal source ofdata.This box gives details of up-regulation of EGFR in thisexperiment. 152 samples havebeen analyzed, of which ofwhich 80 show over-expressionof this gene. The expectednumber of samples withalteration by chance is about4.6. The over-expression istherefore highly significant.
  14. 14. STEP 13Click “all” inExperiments and “all” inTumor type to see theinformation of knowncancer alterations inEGFR in other tumortypes. Go to the tumortype tab.
  15. 15. Note that now we on thepage for EGFR for all tumortypes STEP 14 Click all in Genes. Then go to the genes tab. This table gives information of known cancer alterations in different tumor types found in the 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. 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 continuenavigating over theevidences forinvolvement in cancer ofour group of genes ofinterest.
  17. 17. THANKS FOR USING INTOGEN You will find more tutorials and documentation in www.intogen.org