Oncodomains: A protein domain-centric framework for analyzing rare variants in tumor samples.
The fight against cancer is hindered by its highly heterogeneous nature. Genome-wide sequencing studies have shown that individual malignancies contain many mutations that range from those commonly found in tumor genomes to rare somatic variants present only in a small fraction of lesions. Such rare...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-04-01
|
| Series: | PLoS Computational Biology |
| Online Access: | http://europepmc.org/articles/PMC5398485?pdf=render |
| _version_ | 1818155343826386944 |
|---|---|
| author | Thomas A Peterson Iris Ivy M Gauran Junyong Park DoHwan Park Maricel G Kann |
| author_facet | Thomas A Peterson Iris Ivy M Gauran Junyong Park DoHwan Park Maricel G Kann |
| author_sort | Thomas A Peterson |
| collection | DOAJ |
| description | The fight against cancer is hindered by its highly heterogeneous nature. Genome-wide sequencing studies have shown that individual malignancies contain many mutations that range from those commonly found in tumor genomes to rare somatic variants present only in a small fraction of lesions. Such rare somatic variants dominate the landscape of genomic mutations in cancer, yet efforts to correlate somatic mutations found in one or few individuals with functional roles have been largely unsuccessful. Traditional methods for identifying somatic variants that drive cancer are 'gene-centric' in that they consider only somatic variants within a particular gene and make no comparison to other similar genes in the same family that may play a similar role in cancer. In this work, we present oncodomain hotspots, a new 'domain-centric' method for identifying clusters of somatic mutations across entire gene families using protein domain models. Our analysis confirms that our approach creates a framework for leveraging structural and functional information encapsulated by protein domains into the analysis of somatic variants in cancer, enabling the assessment of even rare somatic variants by comparison to similar genes. Our results reveal a vast landscape of somatic variants that act at the level of domain families altering pathways known to be involved with cancer such as protein phosphorylation, signaling, gene regulation, and cell metabolism. Due to oncodomain hotspots' unique ability to assess rare variants, we expect our method to become an important tool for the analysis of sequenced tumor genomes, complementing existing methods. |
| first_indexed | 2024-12-11T14:40:54Z |
| format | Article |
| id | doaj.art-99f357ce4fc643a5925013301e5e3804 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-11T14:40:54Z |
| publishDate | 2017-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-99f357ce4fc643a5925013301e5e38042022-12-22T01:01:56ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582017-04-01134e100542810.1371/journal.pcbi.1005428Oncodomains: A protein domain-centric framework for analyzing rare variants in tumor samples.Thomas A PetersonIris Ivy M GauranJunyong ParkDoHwan ParkMaricel G KannThe fight against cancer is hindered by its highly heterogeneous nature. Genome-wide sequencing studies have shown that individual malignancies contain many mutations that range from those commonly found in tumor genomes to rare somatic variants present only in a small fraction of lesions. Such rare somatic variants dominate the landscape of genomic mutations in cancer, yet efforts to correlate somatic mutations found in one or few individuals with functional roles have been largely unsuccessful. Traditional methods for identifying somatic variants that drive cancer are 'gene-centric' in that they consider only somatic variants within a particular gene and make no comparison to other similar genes in the same family that may play a similar role in cancer. In this work, we present oncodomain hotspots, a new 'domain-centric' method for identifying clusters of somatic mutations across entire gene families using protein domain models. Our analysis confirms that our approach creates a framework for leveraging structural and functional information encapsulated by protein domains into the analysis of somatic variants in cancer, enabling the assessment of even rare somatic variants by comparison to similar genes. Our results reveal a vast landscape of somatic variants that act at the level of domain families altering pathways known to be involved with cancer such as protein phosphorylation, signaling, gene regulation, and cell metabolism. Due to oncodomain hotspots' unique ability to assess rare variants, we expect our method to become an important tool for the analysis of sequenced tumor genomes, complementing existing methods.http://europepmc.org/articles/PMC5398485?pdf=render |
| spellingShingle | Thomas A Peterson Iris Ivy M Gauran Junyong Park DoHwan Park Maricel G Kann Oncodomains: A protein domain-centric framework for analyzing rare variants in tumor samples. PLoS Computational Biology |
| title | Oncodomains: A protein domain-centric framework for analyzing rare variants in tumor samples. |
| title_full | Oncodomains: A protein domain-centric framework for analyzing rare variants in tumor samples. |
| title_fullStr | Oncodomains: A protein domain-centric framework for analyzing rare variants in tumor samples. |
| title_full_unstemmed | Oncodomains: A protein domain-centric framework for analyzing rare variants in tumor samples. |
| title_short | Oncodomains: A protein domain-centric framework for analyzing rare variants in tumor samples. |
| title_sort | oncodomains a protein domain centric framework for analyzing rare variants in tumor samples |
| url | http://europepmc.org/articles/PMC5398485?pdf=render |
| work_keys_str_mv | AT thomasapeterson oncodomainsaproteindomaincentricframeworkforanalyzingrarevariantsintumorsamples AT irisivymgauran oncodomainsaproteindomaincentricframeworkforanalyzingrarevariantsintumorsamples AT junyongpark oncodomainsaproteindomaincentricframeworkforanalyzingrarevariantsintumorsamples AT dohwanpark oncodomainsaproteindomaincentricframeworkforanalyzingrarevariantsintumorsamples AT maricelgkann oncodomainsaproteindomaincentricframeworkforanalyzingrarevariantsintumorsamples |