[OncoLand Case Study] Find genes that are frequently co-mutated with your gene-of-interest: Co-mutation of TP53 and ATRX when IDH1-R132 is mutated
The IDH1 gene encodes isocitrate dehydrogenase, which is involved in NADPH production, especially in the brain. Mutations in IDH1 are frequently found in low grade and high grade gliomas (Low grade (grade II), anaplastic (grade III), and glioblastoma (GBM, grade IV).). (Research Article: IDH1 and IDH2 Mutations in Gliomas) These mutations play an important role in gliomagenesis and thus have clinical interest. We can query OncoLand to learn about IDH1 mutations, and other genes frequently co-mutated. For details, please refer to our OncoLand case study wiki:
- 1.1 Identify mutation hotspots in a gene of interest
- 1.2 Identify other genes that are co-mutated with your gene of interest
- 1.3 Visualize Co-mutation patterns with the Alteration Omicprint
- 1.4 Visualize expression and alteration patterns with the Custom Query Omicprint
In several cancers, IDH1 is frequently mutated at arginine 132, which alters the enzyme's active site. We can visualize the frequencies of mutations at different sites in each tumor. As we can see, our data confirms that IDH1 arginine 132 is frequently mutated in low grade gliomas (LGG) and glioblastoma (GBM):
The user can create a SampleSet, for example the one shown below, IDH1_mutaion, from the Analytics | Generate Sample Set | Generate Site Mutation Status SampleSet.
With the SampleSet, we can identify the gene mutations that are correlated through Analytics | Integration Analysis | Sample Grouping to Mutation. The test may take a few minutes if all genes are queried, and the results will be available from the Analytics | Open Result Set menu. From the results table, we can rank genes with the PValue from the Fisher Exact Test to identify the correlated genes, for instance ARRX and TP53 in LGG and GBM:
There are several ways to visualize co-mutation frequencies of multiple genes. While the "Alteration Distribution" displays the number of samples mutated in any gene of the GeneSet, "Somatic Co-mutation Frequencies" will display the distribution of samples with different mutation loads. The "Alteration Omicprint" efficiently displays per-sample mutation status of one, ten, or even hundreds of genes. You can also generate custom Omicprinst based on custom queries if you want to query mutation status. Please check out our case study tutorial videos to learn how to perform the analysis.