cancer gene prioritization

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TUTORIAL - CANCER GENE PRIORITIZATION Prioritize a list of candidate genes based on CGPrio probabilities and oncogenomic alterations

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Page 1: Cancer Gene Prioritization

TUTORIAL - CANCER GENE PRIORITIZATION

Prioritize a list of candidate genes based on CGPrio probabilities and oncogenomic alterations

Page 2: Cancer Gene Prioritization

Go to www.intogen.org& Click Browser

STEP 1

Page 3: Cancer Gene Prioritization

Click on Upload filter.

STEP 2

Page 4: Cancer Gene Prioritization

Paste the list of genes to prioritize.You can also upload a file with the list of genes.

STEP 4

Select the type of gene IDs for the list that you are providing

STEP 3

For this tutorial we are going to load a list of 37 candidate cancer genes identified after a mutation screening of 20661 human genes in 22 human tumor samples of Glioblastoma multiforme.

(Parson et al Science 2008)

NOTE

Click on Create filter

STEP 5

Page 5: Cancer Gene Prioritization

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 on computational classifiers that use different combinations of sequence and functional data including sequence conservation, protein domains and interactions, and regulatory data. For more information see Furney et al., NAR 2008

STEP 6

This indicates that the filter is applied. You can click the red x to eliminate the filter and return to the list of all genes.

With these links you can go to the next page to see the rest of genes. In total there are 37.

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.

This table informs if the gene is in the Cancer Gene Census of the Sanger Center and which type of mutations are annotated there.

Page 6: Cancer Gene Prioritization

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.

White means that there is no data for this gene in this tumor type

Color scale of corrected p-values:Gray = no significantly alteredRed/Yellow = significantly altered

The colors indicate significance. Color toward red means that this gene is significantly altered in this tumor type.

Gray means that this gene is not significantly altered (CNA gain in this case) in this tumor type

Page 7: Cancer Gene Prioritization

STEP 5

This column gives information on mutations in these genes found and studied in this tumor type. This information is imported from COSMIC.

You can sort the table by clicking the title of any column, to have the genes with lowest or highest values on top. Click Onco twice to sort by those genes with the highest oncogene prediction rank.

STEP 7

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You can sort the table by clicking to the title of any column, to have the genes more significantly altered in the top. Click Up to sort by up-regulation.

STEP 8

For any of the genes you can get detailed information. For example click on the Ensembl ID for EGFR .

STEP 9

Now in the top of the table we have the genes that are more significantly up-regulated in brain and related tumors

Note that you can retrieve the data in a tabulated file by clicking on ‘CSV file’ under ‘Export'.

Page 9: Cancer Gene Prioritization

Note that now we are on the page for EGFR for brain and related tumor types.

This box shows some gene details and link to ensembl

This box shows details of mutations of EGFR in brain cancer. The number of samples with mutations (103), the number of samples analyzed (1643) and the link to COSMIC for this gene.

This box shows details of prediction ranks for EGFR gene obtained with CGPrio for the different sets of properties analyzed.This box indicate that this gene

is in the Cancer Gene Census, and it give details about the type of mutations identified.

Click on Tumor types Tab.

STEP 10

Page 10: Cancer Gene Prioritization

This table gives information on the alterations found in EGFR in different morphologies of brain cancer. Note that this gene is amplified and up-regulated in many morphologies.

Now click on Experiments Tab to see details

STEP 11

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This is the list of experiments that have analyzed EGFR in brain cancer and related tissues.

N = number of samples analyzed

The color indicates that the region of this gene is amplified in a significant number of the 171 samples analyzed.

White cells means no data. In this case, it means that this experiment has not analyzed transcriptomic alterations

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Click on the experiment by Sun L et al to see the details.

STEP 13

Click Up to have the experiments on top in which this gene is significantly up-regulated.

STEP 12

Page 13: Cancer Gene Prioritization

Note that now we are on the page of EGFR for a particular experiment of brain cancer.

This box gives details of up-regulation of EGFR in this experiment. 152 samples have been analyzed, of which of which 80 show over-expression of this gene. The expected number of samples with alteration by chance is about 4.6. The over-expression is therefore highly significant.

This box gives details of the experiment, including authors, title and link to the publication or original source of data.

Page 14: Cancer Gene Prioritization

Click “all” in Experiments and “all” in Tumor type to see the information of known cancer alterations in EGFR in other tumor types. Go to the tumor type tab.

STEP 13

Page 15: Cancer Gene Prioritization

Note that now we on the page for EGFR for all tumor types

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.

Click all in Genes.Then go to the genes tab.

STEP 14

Page 16: Cancer Gene Prioritization

The filter is still applied, so we can continue navigating over the evidences for involvement in cancer of our group of genes of interest.

Now we see the page showing all the tumor types for all genes included in the filter and all tumor types.

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THANKS FOR USING INTOGEN

You will find more tutorials and documentation in www.intogen.org