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HotSpotter: efficient visualization of driver mutations.

Roszik J, Woodman SE - BMC Genomics (2014)

Bottom Line: The relative frequency of a particular mutation within a gene is typically used as a criterion for identifying a driver mutation.However, driver mutations may occur with relative infrequency at a particular site, but cluster within a region of the gene.This allows the user to identify potential driver mutations that are less frequent in a cancer or are localized in a hotspot region of relatively infrequent mutations.

View Article: PubMed Central - PubMed

Affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 7455 Fannin St, Houston, TX 77054, USA. swoodman@mdanderson.org.

ABSTRACT

Background: Driver mutations are positively selected during the evolution of cancers. The relative frequency of a particular mutation within a gene is typically used as a criterion for identifying a driver mutation. However, driver mutations may occur with relative infrequency at a particular site, but cluster within a region of the gene. When analyzing across different cancers, particular mutation sites or mutations within a particular region of the gene may be of relatively low frequency in some cancers, but still provide selective growth advantage.

Results: This paper presents a method that allows rapid and easy visualization of mutation data sets and identification of potential gene mutation hotspot sites and/or regions. As an example, we identified hotspot regions in the NFE2L2 gene that are potentially functionally relevant in endometrial cancer, but would be missed using other analyses.

Conclusions: HotSpotter is a quick, easy-to-use visualization tool that delivers gene identities with associated mutation locations and frequencies overlaid upon a large cancer mutation reference set. This allows the user to identify potential driver mutations that are less frequent in a cancer or are localized in a hotspot region of relatively infrequent mutations.

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Related in: MedlinePlus

HotSpotter identification of potential mutation hotspot sites/regions in the TCGA UCEC data set. The y-axis demarcates the names of genes and frequency of mutations within each gene. The x-axis demarcates the amino acid position within the protein product for each mutation. Orange dots (intentionally large for quick visualization) and their vertical position represent the frequency of mutation at a specific site in the UCEC test set. Blue dots (intentionally smaller) and their vertical position represent the frequency of mutations at specific sites in the COSMIC dataset. For non-substitution mutations, the first amino acid at which the alteration occurs is used as the “position”.
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Fig2: HotSpotter identification of potential mutation hotspot sites/regions in the TCGA UCEC data set. The y-axis demarcates the names of genes and frequency of mutations within each gene. The x-axis demarcates the amino acid position within the protein product for each mutation. Orange dots (intentionally large for quick visualization) and their vertical position represent the frequency of mutation at a specific site in the UCEC test set. Blue dots (intentionally smaller) and their vertical position represent the frequency of mutations at specific sites in the COSMIC dataset. For non-substitution mutations, the first amino acid at which the alteration occurs is used as the “position”.

Mentions: Figure 2 shows how HotSpotter illustrated potential mutation hotspot amino acid sites and/or regions derived from the TCGA UCEC samples (The Tableau interface can be downloaded at the following address: http://public.tableausoftware.com/views/HotSpotter-TCGA_UCEC_selected/Selectedgenes). The y-axis demarcates the names of genes and the frequency of specific amino acid alterations arising from specific mutations (hereafter, termed ‘mutations’) within each gene. The x-axis demarcates the amino acid position within the inferred protein product for each mutation.


HotSpotter: efficient visualization of driver mutations.

Roszik J, Woodman SE - BMC Genomics (2014)

HotSpotter identification of potential mutation hotspot sites/regions in the TCGA UCEC data set. The y-axis demarcates the names of genes and frequency of mutations within each gene. The x-axis demarcates the amino acid position within the protein product for each mutation. Orange dots (intentionally large for quick visualization) and their vertical position represent the frequency of mutation at a specific site in the UCEC test set. Blue dots (intentionally smaller) and their vertical position represent the frequency of mutations at specific sites in the COSMIC dataset. For non-substitution mutations, the first amino acid at which the alteration occurs is used as the “position”.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4265503&req=5

Fig2: HotSpotter identification of potential mutation hotspot sites/regions in the TCGA UCEC data set. The y-axis demarcates the names of genes and frequency of mutations within each gene. The x-axis demarcates the amino acid position within the protein product for each mutation. Orange dots (intentionally large for quick visualization) and their vertical position represent the frequency of mutation at a specific site in the UCEC test set. Blue dots (intentionally smaller) and their vertical position represent the frequency of mutations at specific sites in the COSMIC dataset. For non-substitution mutations, the first amino acid at which the alteration occurs is used as the “position”.
Mentions: Figure 2 shows how HotSpotter illustrated potential mutation hotspot amino acid sites and/or regions derived from the TCGA UCEC samples (The Tableau interface can be downloaded at the following address: http://public.tableausoftware.com/views/HotSpotter-TCGA_UCEC_selected/Selectedgenes). The y-axis demarcates the names of genes and the frequency of specific amino acid alterations arising from specific mutations (hereafter, termed ‘mutations’) within each gene. The x-axis demarcates the amino acid position within the inferred protein product for each mutation.

Bottom Line: The relative frequency of a particular mutation within a gene is typically used as a criterion for identifying a driver mutation.However, driver mutations may occur with relative infrequency at a particular site, but cluster within a region of the gene.This allows the user to identify potential driver mutations that are less frequent in a cancer or are localized in a hotspot region of relatively infrequent mutations.

View Article: PubMed Central - PubMed

Affiliation: Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 7455 Fannin St, Houston, TX 77054, USA. swoodman@mdanderson.org.

ABSTRACT

Background: Driver mutations are positively selected during the evolution of cancers. The relative frequency of a particular mutation within a gene is typically used as a criterion for identifying a driver mutation. However, driver mutations may occur with relative infrequency at a particular site, but cluster within a region of the gene. When analyzing across different cancers, particular mutation sites or mutations within a particular region of the gene may be of relatively low frequency in some cancers, but still provide selective growth advantage.

Results: This paper presents a method that allows rapid and easy visualization of mutation data sets and identification of potential gene mutation hotspot sites and/or regions. As an example, we identified hotspot regions in the NFE2L2 gene that are potentially functionally relevant in endometrial cancer, but would be missed using other analyses.

Conclusions: HotSpotter is a quick, easy-to-use visualization tool that delivers gene identities with associated mutation locations and frequencies overlaid upon a large cancer mutation reference set. This allows the user to identify potential driver mutations that are less frequent in a cancer or are localized in a hotspot region of relatively infrequent mutations.

Show MeSH
Related in: MedlinePlus