BRCA1 Circos: a visualisation resource for functional analysis of missense variants.

J Med Genet 2015 Apr 2;52(4):224-30. Epub 2015 Feb 2.

Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.

Background: Inactivating germline mutations in the tumour suppressor gene BRCA1 are associated with a significantly increased risk of developing breast and ovarian cancer. A large number (>1500) of unique BRCA1 variants have been identified in the population and can be classified as pathogenic, non-pathogenic or as variants of unknown significance (VUS). Many VUS are rare missense variants leading to single amino acid changes. Their impact on protein function cannot be directly inferred from sequence information, precluding assessment of their pathogenicity. Thus, functional assays are critical to assess the impact of these VUS on protein activity. BRCA1 is a multifunctional protein and different assays have been used to assess the impact of variants on different biochemical activities and biological processes.

Methods And Results: To facilitate VUS analysis, we have developed a visualisation resource that compiles and displays functional data on all documented BRCA1 missense variants. BRCA1 Circos is a web-based visualisation tool based on the freely available Circos software package. The BRCA1 Circos web tool (http://research.nhgri.nih.gov/bic/circos/) aggregates data from all published BRCA1 missense variants for functional studies, harmonises their results and presents various functionalities to search and interpret individual-level functional information for each BRCA1 missense variant.

Conclusions: This research visualisation tool will serve as a quick one-stop publically available reference for all the BRCA1 missense variants that have been functionally assessed. It will facilitate meta-analysis of functional data and improve assessment of pathogenicity of VUS.

Download full-text PDF

Source
http://dx.doi.org/10.1136/jmedgenet-2014-102766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392196PMC
April 2015
57 Reads
9 Citations
6.340 Impact Factor

Publication Analysis

Top Keywords

missense variants
20
brca1 missense
16
brca1 circos
12
brca1
10
visualisation tool
8
variants
8
assessment pathogenicity
8
assess impact
8
functional data
8
visualisation resource
8
missense
6
functional
6
vus
5
web-based visualisation
4
vus analysis
4
facilitate vus
4
processesmethods facilitate
4
analysis developed
4
biological processesmethods
4
activities biological
4

References

(Supplied by CrossRef)
Genetic analysis of breast cancer in the cancer and steroid hormone study
Claus et al.
Am J Hum Genet 1991
Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. The Breast Cancer Linkage Consortium
Easton et al.
Am J Hum Genet 1993
Direct-to-patient BRCA1 testing: the Twoj Styl experience
Gronwald et al.
Breast Cancer Res Treat 2006
A prospective study of breast cancer risk in relatives of BRCA1/BRCA2 mutation carriers
Rowan et al.
J Med Genet 2007

Similar Publications