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dc.contributor.author
Nguyen, An-phi
dc.contributor.author
Nicoletti, Paola
dc.contributor.author
Arnol, Damien
dc.contributor.author
Califano, Andrea
dc.contributor.author
Rodriguez Martinez, María
dc.date.accessioned
2020-10-13T12:01:55Z
dc.date.available
2020-09-09T03:04:27Z
dc.date.available
2020-09-09T12:36:30Z
dc.date.available
2020-10-13T12:01:55Z
dc.date.issued
2020-08-04
dc.identifier.issn
2296-4185
dc.identifier.other
10.3389/fbioe.2020.00798
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/439171
dc.identifier.doi
10.3929/ethz-b-000439171
dc.description.abstract
In the last decade, a large number of genome-wide association studies have uncovered many single-nucleotide polymorphisms (SNPs) that are associated with complex traits and confer susceptibility to diseases, such as cancer. However, so far only a few heritable traits with medium-to-high penetrance have been identified. The vast majority of the discovered variants only leads to disease in combination with other still unknown factors. Furthermore, while many studies aimed to link the effect of SNPs to changes in molecular phenotypes, the analysis has been often focused on testing associations between a single SNP and a transcript, hence disregarding the dysregulation of gene regulatory networks that has been shown to play an essential role in disease onset, notably in cancer. Here we take a systems biology approach and develop GVITamIN (Genetic VarIaTIoN functional analysis tool), a new statistical and computational approach to characterize the effect of a SNP on both genes and transcriptional regulatory programs. GVITamIN exploits a novel statistical approach to combine the usually small effect of disease-susceptibility SNPs, and reveals important potential oncogenic mechanisms, hence taking one step further in the direction of understanding the SNP mechanism of action. We apply GVITamIN on a breast cancer cohort and identify well-known cancer-related transcription factors, such as CTCF, LEF1, and FOXA1, as TFs dysregulated by breast cancer-associated SNPs. Furthermore, our results reveal that SNPs located on the RAD51B gene are significantly associated with an abnormal regulatory activity, suggesting a pivotal role for homologous recombination repair mechanisms in breast cancer.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Frontiers Media SA
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
cancer-susceptibility SNP
en_US
dc.subject
SNP mechanism of action
en_US
dc.subject
transcription factor dysregulation
en_US
dc.subject
breast cancer
en_US
dc.subject
multi-omics integration
en_US
dc.subject
nonparametric hypothesis test
en_US
dc.subject
p-value combination
en_US
dc.title
Identifying the Potential Mechanism of Action of SNPs Associated With Breast Cancer Susceptibility With GVITamIN
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
ethz.journal.title
Frontiers in Bioengineering and Biotechnology
ethz.journal.volume
8
en_US
ethz.journal.abbreviated
Front. bioeng. biotechnol.
ethz.pages.start
798
en_US
ethz.size
13 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.grant
PERSONALIZED ENGINE FOR CANCER INTEGRATIVE STUDY AND EVALUATION, a tool for cancer patient risk-stratification and pers. drug selection through multi-omic data integration.
en_US
ethz.identifier.wos
ethz.publication.place
Lausanne
en_US
ethz.publication.status
published
en_US
ethz.grant.agreementno
668858
ethz.grant.fundername
SBFI
ethz.grant.funderDoi
10.13039/501100007352
ethz.grant.program
H2020
ethz.date.deposited
2020-09-09T03:04:37Z
ethz.source
WOS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2020-09-09T12:36:41Z
ethz.rosetta.lastUpdated
2020-09-09T12:36:41Z
ethz.rosetta.exportRequired
true
ethz.rosetta.versionExported
true
ethz.COinS
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