cancer gene prioritization

Download Cancer Gene Prioritization

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  • 1. TUTORIAL - CANCER GENE PRIORITIZATIONPrioritize a list ofcandidate genes basedon CGPrio probabilitiesand oncogenomicalterations

2. STEP 1Go to www.intogen.org& Click Browser 3. STEP 2Click on Upload filter. 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. STEP 6Select the type of cancer inwhich you are interested. Inthis case we will select braintumors since we are studying alist of candidate cancer genesfor glioblastoma.These values are based onpredictions by CGPrio method.Genes with a higher probabilityrank are more likely to beinvolved in cancer.The CGPrio method is based onThis indicates that the computational classifiers thatfilter is applied. You canuse different combinations ofclick the red x tosequence and functional dataeliminate the filter andincluding sequencereturn to the list of all conservation, protein domainsgenes.and interactions, and regulatorydata. For more information seeFurney et al., NAR 2008This table informs if thegene is in the CancerGene Census of theWith these links youSanger Center and can go to the nextwhich type of mutations page to see the restare annotated there.of genes. In totalthere are 37. 6. Note that now we are on the page for brain and related tumor typesThis table gives asummary of alterationsfound for each gene inthe 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 thisWhite means that gene is not significantly there is no data altered (CNA gain in this for this gene in case) in this tumor typethis tumor type 7. STEP 7STEP 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. STEP 8Now in the top of the table You can sort the table bywe have the genes thatclicking to the title of anyare more significantly up-column, to have the genesregulated in brain andmore significantly altered inrelated tumorsthe top. Click Up to sort byup-regulation. STEP 9For any of the genes youcan get detailedinformation. For exampleclick on the Ensembl ID forEGFR .Note that you canretrieve the data ina tabulated file byclicking on CSV fileunder Export. 9. Note that now we are onthe page for EGFR forbrain and related tumortypes. 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 obtainedThis box shows with CGPrio for thesome gene details different sets ofThis box indicate that this geneand link to ensembl properties analyzed.is in the Cancer Gene Census,and it give details about the typeof mutations identified. 10. STEP 11Now click onExperiments Tab tosee detailsThis table gives information on thealterations found in EGFR indifferent morphologies of braincancer. Note that this gene isamplified and up-regulated inmany morphologies. 11. This is the list of experimentsthat have analyzed EGFR inbrain cancer and relatedtissues.The color indicates N = numberthat the region ofof samplesthis gene isanalyzedamplified 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. STEP 12Click Up to have theexperiments on top in whichthis gene is significantly up-regulated. STEP 13Click on theexperiment by Sun Let al to see thedetails. 13. Note that now weare on the page ofEGFR for a particularexperiment of braincancer.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. STEP 13Click all inExperiments and all inTumor type to see theinformation of knowncancer alterations inEGFR in other tumortypes. Go to the tumortype tab. 15. Note that now we on thepage for EGFR for all tumortypesSTEP 14Click all in Genes.Then go to the genestab.This table givesinformation of knowncancer alterations indifferent tumor typesfound in the EGFR gene.In this case we can seethat the region of thisgene is significantlyamplified (gained) inseveral tumor types, it istranscriptionally alteredin some and a number ofmutations have beenfound in different tumortypes. 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. THANKS FOR USING INTOGEN You will find more tutorials and documentation in www.intogen.org