title: BRCA1 Circos: a visualisation resource for functional analysis of missense variants.
abstract: 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.
  
  
  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.
authors: Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA University of South Florida Cancer Biology PhD Program, Tampa, Florida, USA.
authors: Ankita
authors: A
authors: Jhuraney
authors: Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA Genome Technology Branch, National Human Genome Research Institute, Bethesda, Maryland, USA.
authors: Aneliya
authors: A
authors: Velkova
authors: Frederick National Laboratory for Cancer Research, National Cancer Institute, Fredrick, Maryland, USA.
authors: Randall C
authors: RC
authors: Johnson
authors: Frederick National Laboratory for Cancer Research, National Cancer Institute, Fredrick, Maryland, USA.
authors: Bailey
authors: B
authors: Kessing
authors: Instituto Federal de Educação, Ciência e Tecnologia, Rio de Janeiro, RJ, Brazil Instituto Nacional de Câncer, Divisão de Farmacologia, Rio de Janeiro, Brazil.
authors: Renato S
authors: RS
authors: Carvalho
authors: Genetics and Population Health Division, QIMR, BNE, Brisbane, Queensland, Australia.
authors: Phillip
authors: P
authors: Whiley
authors: Genetics and Population Health Division, QIMR, BNE, Brisbane, Queensland, Australia.
authors: Amanda B
authors: AB
authors: Spurdle
authors: Department of Human Genetics, Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands.
authors: Maaike P G
authors: MP
authors: Vreeswijk
authors: Service de Génétique, Institut Curie, Hôpital René Huguenin, Paris, France.
authors: Sandrine M
authors: SM
authors: Caputo
authors: Institut Curie, Université Pierre et Marie Curie, Paris, France.
authors: Gael A
authors: GA
authors: Millot
authors: Fundación Pública Galega de Medicina Xenómica, Santiago, Spain.
authors: Ana
authors: A
authors: Vega
authors: Department of Biochemistry, University of Alberta, Alberta, Canada.
authors: Nicolas
authors: N
authors: Coquelle
authors: Instituto di Fisiologia Clinica, Consiglio Nazionale delle Ricerche, Pisa, Italy.
authors: Alvaro
authors: A
authors: Galli
authors: University of Southampton, Southampton, UK.
authors: Diana
authors: D
authors: Eccles
authors: Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, the Netherlands.
authors: Marinus J
authors: MJ
authors: Blok
authors: Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors: Tuya
authors: T
authors: Pal
authors: Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands.
authors: Rob B
authors: RB
authors: van der Luijt
authors: CIBERER, Madrid, Spain.
authors: Marta
authors: M
authors: Santamariña Pena
authors: Department of Population Sciences, Beckman Research Institute of the City of Hope, Duarte, California, USA.
authors: Susan L
authors: SL
authors: Neuhausen
authors: University of Miami Medical School, Miami, Florida, USA.
authors: Talia
authors: T
authors: Donenberg
authors: Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
authors: Eva
authors: E
authors: Machackova
authors: Salisbury District Hospital, Salisbury, Wiltshire, UK.
authors: Simon
authors: S
authors: Thomas
authors: International Agency for Research on Cancer, Lyon, France.
authors: Maxime
authors: M
authors: Vallée
authors: Department of Laboratory Medicine and Pathology, and Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
authors: Fergus J
authors: FJ
authors: Couch
authors: Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah, USA.
authors: Sean V
authors: SV
authors: Tavtigian
authors: Department of Biochemistry, University of Alberta, Alberta, Canada.
authors: J N Mark
authors: JN
authors: Glover
authors: Instituto Federal de Educação, Ciência e Tecnologia, Rio de Janeiro, RJ, Brazil Instituto Nacional de Câncer, Divisão de Farmacologia, Rio de Janeiro, Brazil.
authors: Marcelo A
authors: MA
authors: Carvalho
authors: Genome Technology Branch, National Human Genome Research Institute, Bethesda, Maryland, USA.
authors: Lawrence C
authors: LC
authors: Brody
authors: Center for Cancer Research, National Cancer Institute, Frederick, Maryland, USA.
authors: Shyam K
authors: SK
authors: Sharan
authors: Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors: Alvaro N
authors: AN
authors: Monteiro
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics; D019295:Computational Biology / Q000379:methods*; D003196:Computer Graphics; D004252:DNA Mutational Analysis; D003628:Database Management Systems; D030541:Databases, Genetic; D066264:Datasets as Topic; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D020407:Internet; D020125:Mutation, Missense; D010051:Ovarian Neoplasms / Q000235:genetics; D012984:Software
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human
keywords: BRCA1; Cancer: breast; Clinical genetics; Molecular genetics
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