SpadaHC: a database to improve the classification of variants in hereditary cancer genes in the Spanish population
Por:
Moreno-Cabrera, JM, Feliubadaló, L, Pineda, M, Prada-Dacasa, P, Ramos-Muntada, M, Del Valle, J, Brunet, J, Gel, B, Currás-Freixes, M, Calsina, B, Salazar-Hidalgo, ME, Rodríguez-Balada, M, Roig, B, Fernández-Castillejo, S, Domínguez, M, Ledo, M, Sanz, MI, Castillejo, A, Dámaso, E, Soto, JL, de Miguel, M, Calero, B, Sánchez-Zapardiel, JM, Ramon, T, Lasa, A, Gisbert-Beamud, A, López-Novo, A, Ruiz-Ponte, C, Potrony, M, Alvarez-Mora, M, Osorio, A, Lorda-Sánchez, I, Robledo, M, Cascon, A, Ruiz, A, Spataro, N, Hernan, I, Borràs, E, Moles-Fernández, A, Earl, J, Cadiñanos, J, Sánchez-Heras, AB, Bigas, A, Capellá, G, Lazaro, C
Publicada:
4 jul 2024
Ahead of Print:
1 jul 2024
Resumen:
Accurate classification of genetic variants is crucial for clinical decision-making in hereditary cancer. In Spain, genetic diagnostic laboratories have traditionally approached this task independently due to the lack of a dedicated resource. Here we present SpadaHC, a web-based database for sharing variants in hereditary cancer genes in the Spanish population. SpadaHC is implemented using a three-tier architecture consisting of a relational database, a web tool and a bioinformatics pipeline. Contributing laboratories can share variant classifications and variants from individuals in Variant Calling Format (VCF) format. The platform supports open and restricted access, flexible dataset submissions, automatic pseudo-anonymization, VCF quality control, variant normalization and liftover between genome builds. Users can flexibly explore and search data, receive automatic discrepancy notifications and access SpadaHC population frequencies based on many criteria. In February 2024, SpadaHC included 18 laboratory members, storing 1.17 million variants from 4306 patients and 16 343 laboratory classifications. In the first analysis of the shared data, we identified 84 genetic variants with clinically relevant discrepancies in their classifications and addressed them through a three-phase resolution strategy. This work highlights the importance of data sharing to promote consistency in variant classifications among laboratories, so patients and family members can benefit from more accurate clinical management.Database URL: https://spadahc.ciberisciii.es/
Overview of SpadaHC and its main views. (A) List of existing variants in SpadaHC (in the image, search for the ATM gene). The 'Expert Cl.' column shows the classification made by a group of experts; the 'Lab Cl.' column shows a summary of the classifications made by the laboratories. (B) Allele frequency of a variant in the SpadaHC population according to clinical suspicion and sex. (C) Classifications provided by the laboratories for a variant. (D) List of patients carrying a variant. (E) Histogram showing the coverage and frequency (allele balance) with which the variant was detected in carrier patients. Alt text: SpadaHC overview; laboratories can share datasets of variant classifications (Excel) and variants from individuals (VCFs + Excel). The datasets undergo quality control, bioinformatics pipeline annotation and database integration before being displayed in SpadaHC. The graphical abstract also shows five views of SpadaHC.
Filiaciones:
Moreno-Cabrera, JM:
Inst Invest Biomed Bellvitge IDIBELL ONCOBELL, Catalan Inst Oncol, Hereditary Canc Program, Barcelona 08908, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Canc CIBERONC, Monforte de Lemos 3-5, Madrid 28029, Spain
Catalan Inst Oncol ICO, Oncol Data Analyt Program ODAP, Barcelona 08908, Spain
Feliubadaló, L:
Inst Invest Biomed Bellvitge IDIBELL ONCOBELL, Catalan Inst Oncol, Hereditary Canc Program, Barcelona 08908, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Canc CIBERONC, Monforte de Lemos 3-5, Madrid 28029, Spain
Pineda, M:
Inst Invest Biomed Bellvitge IDIBELL ONCOBELL, Catalan Inst Oncol, Hereditary Canc Program, Barcelona 08908, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Canc CIBERONC, Monforte de Lemos 3-5, Madrid 28029, Spain
Prada-Dacasa, P:
Inst Invest Biomed Bellvitge IDIBELL ONCOBELL, Catalan Inst Oncol, Hereditary Canc Program, Barcelona 08908, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Canc CIBERONC, Monforte de Lemos 3-5, Madrid 28029, Spain
Ramos-Muntada, M:
Inst Invest Biomed Bellvitge IDIBELL ONCOBELL, Catalan Inst Oncol, Hereditary Canc Program, Barcelona 08908, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Canc CIBERONC, Monforte de Lemos 3-5, Madrid 28029, Spain
Del Valle, J:
Inst Invest Biomed Bellvitge IDIBELL ONCOBELL, Catalan Inst Oncol, Hereditary Canc Program, Barcelona 08908, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Canc CIBERONC, Monforte de Lemos 3-5, Madrid 28029, Spain
Brunet, J:
Inst Invest Biomed Bellvitge IDIBELL ONCOBELL, Catalan Inst Oncol, Hereditary Canc Program, Barcelona 08908, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Canc CIBERONC, Monforte de Lemos 3-5, Madrid 28029, Spain
Gel, B:
Germans Trias i Pujol Res Inst PMPPC IGTP, Program Predict & Personalized Med Canc, Hereditary Canc Grp, Campus Can Ruti,Ctra Can Ruti,Cami Escoles,S-N, Badalona 08916, Spain
Currás-Freixes, M:
Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Program, Familial Canc Clin Unit, Melchor Fernandez Almagro 3, Madrid 28029, Spain
Calsina, B:
Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Program, Familial Canc Clin Unit, Melchor Fernandez Almagro 3, Madrid 28029, Spain
Salazar-Hidalgo, ME:
Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Program, Familial Canc Clin Unit, Melchor Fernandez Almagro 3, Madrid 28029, Spain
Rodríguez-Balada, M:
Univ Rovira i Virgili URV, Hosp Univ St Joan de Reus HUSJR, Inst Oncol Catalunya Sud IOCS, Inst Invest Sanitaria Pere Virgili IISPV, Dr Josep Laporte 2, Reus 43204, Spain
Roig, B:
Univ Rovira i Virgili URV, Hosp Univ St Joan de Reus HUSJR, Inst Oncol Catalunya Sud IOCS, Inst Invest Sanitaria Pere Virgili IISPV, Dr Josep Laporte 2, Reus 43204, Spain
Fernández-Castillejo, S:
Univ Rovira i Virgili URV, Hosp Univ St Joan de Reus HUSJR, Inst Oncol Catalunya Sud IOCS, Inst Invest Sanitaria Pere Virgili IISPV, Dr Josep Laporte 2, Reus 43204, Spain
Domínguez, M:
Univ Valladolid, Spanish Natl Res Council IBGM UVa CSIC, Unit Excellence Inst Biomed & Mol Genet, Canc Genet Grp, Sanz & Fores 3, Valladolid 47003, Spain
Ledo, M:
Univ Valladolid, Spanish Natl Res Council IBGM UVa CSIC, Unit Excellence Inst Biomed & Mol Genet, Canc Genet Grp, Sanz & Fores 3, Valladolid 47003, Spain
Sanz, MI:
Univ Valladolid, Spanish Natl Res Council IBGM UVa CSIC, Unit Excellence Inst Biomed & Mol Genet, Canc Genet Grp, Sanz & Fores 3, Valladolid 47003, Spain
Castillejo, A:
Hosp Gen Univ Elche, Fdn Fomento Invest Sanitaria & Biomed Comunitat Va, Unidad Genet Mol, AvCatalunya 21, Elche 03203, Spain
Dámaso, E:
Hosp Gen Univ Elche, Fdn Fomento Invest Sanitaria & Biomed Comunitat Va, Unidad Genet Mol, AvCatalunya 21, Elche 03203, Spain
Soto, JL:
Hosp Gen Univ Elche, Fdn Fomento Invest Sanitaria & Biomed Comunitat Va, Unidad Genet Mol, AvCatalunya 21, Elche 03203, Spain
de Miguel, M:
Hosp Univ 12 Octubre, Serv Bioquim Clin Anal Clin, Lab Canc Hereditario, Av Cordoba S-N, Madrid 28041, Spain
Calero, B:
Hosp Univ 12 Octubre, Serv Bioquim Clin Anal Clin, Lab Canc Hereditario, Av Cordoba S-N, Madrid 28041, Spain
Sánchez-Zapardiel, JM:
Hosp Univ 12 Octubre, Serv Bioquim Clin Anal Clin, Lab Canc Hereditario, Av Cordoba S-N, Madrid 28041, Spain
Ramon, T:
Hosp Santa Creu & Sant Pau, Familial Canc Clin, Med Oncol, St Quinti 89, Barcelona 08041, Spain
Lasa, A:
Hosp Santa Creu & Sant Pau, Genet Dept, St Quinti 89, Barcelona 08041, Spain
Inst Salud Carlos III, Biomed Network Res Ctr Rare Dis CIBERER, Monforte de Lemos 3-5, Madrid 28029, Spain
Gisbert-Beamud, A:
Inst Recerca St Pau IR St Pau, St Quinti 77, Barcelona 08041, Spain
López-Novo, A:
Fdn Publ Galega Med Xen SERGAS, Grp Med Xen USC, Inst Invest Sanitaria St iago, Av Barcelona S-N, Santiago De Compostela 15706, Spain
Ruiz-Ponte, C:
Inst Salud Carlos III, Biomed Network Res Ctr Rare Dis CIBERER, Monforte de Lemos 3-5, Madrid 28029, Spain
Fdn Publ Galega Med Xen SERGAS, Grp Med Xen USC, Inst Invest Sanitaria St iago, Av Barcelona S-N, Santiago De Compostela 15706, Spain
Potrony, M:
Inst Salud Carlos III, Biomed Network Res Ctr Rare Dis CIBERER, Monforte de Lemos 3-5, Madrid 28029, Spain
Univ Barcelona, Hosp Clin Barcelona, Biochem & Mol Genet Dept, Rossello 149, Barcelona 08036, Spain
Univ Barcelona, Fundacio Recerca Clin Barcelona Inst Invest Biomed, Rossello 149, Barcelona 08036, Spain
Alvarez-Mora, M:
Inst Salud Carlos III, Biomed Network Res Ctr Rare Dis CIBERER, Monforte de Lemos 3-5, Madrid 28029, Spain
Univ Barcelona, Hosp Clin Barcelona, Biochem & Mol Genet Dept, Rossello 149, Barcelona 08036, Spain
Univ Barcelona, Fundacio Recerca Clin Barcelona Inst Invest Biomed, Rossello 149, Barcelona 08036, Spain
Osorio, A:
Inst Salud Carlos III, Biomed Network Res Ctr Rare Dis CIBERER, Monforte de Lemos 3-5, Madrid 28029, Spain
Hosp Univ Fdn Jimenez Diaz IIS FJD, Dept Genet & Genomica, Av Reyes Catolicos 2, Madrid 28040, Spain
Lorda-Sánchez, I:
Inst Salud Carlos III, Biomed Network Res Ctr Rare Dis CIBERER, Monforte de Lemos 3-5, Madrid 28029, Spain
Hosp Univ Fdn Jimenez Diaz IIS FJD, Dept Genet & Genomica, Av Reyes Catolicos 2, Madrid 28040, Spain
Robledo, M:
Inst Salud Carlos III, Biomed Network Res Ctr Rare Dis CIBERER, Monforte de Lemos 3-5, Madrid 28029, Spain
Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Program, Hereditary Endocrine Canc Grp, Melchor Fernandez Almagro 3, Madrid 28029, Spain
Cascon, A:
Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Program, Hereditary Endocrine Canc Grp, Melchor Fernandez Almagro 3, Madrid 28029, Spain
Ruiz, A:
Univ Autonoma Barcelona, Inst Invest & Innovacio Parc Tauli CERCA I3PT, Genet Lab, Ctr Genom Med, Parc Tauli Hosp Univ,Placa Torre Aigua,S-N, Sabadell 08208, Spain
Spataro, N:
Univ Autonoma Barcelona, Inst Invest & Innovacio Parc Tauli CERCA I3PT, Genet Lab, Ctr Genom Med, Parc Tauli Hosp Univ,Placa Torre Aigua,S-N, Sabadell 08208, Spain
Hernan, I:
Consorci Sanit Terrassa, Mol Genet Unit, Ctra Torrebon S-N, Terrassa 08227, Spain
Borràs, E:
Consorci Sanit Terrassa, Mol Genet Unit, Ctra Torrebon S-N, Terrassa 08227, Spain
Moles-Fernández, A:
Vall dHebron Hosp Univ, Dept Clin & Mol Genet, Vall dHebron Barcelona Hosp Campus,Pg Vall dHebron, Barcelona 08035, Spain
Vall dHebron Hosp Univ, Vall dHebron Inst Recerca VHIR, Med Genet Grp, Vall dHebron Barcelona Hosp Campus,Pg Vall dHebron, Barcelona 08035, Spain
Earl, J:
Inst Salud Carlos III, Ctr Invest Biomed Red Canc CIBERONC, Monforte de Lemos 3-5, Madrid 28029, Spain
Ramon y Cajal Hlth Res Inst IRYCIS, Biomarkers & Personalized Approach Canc Grp BioPAC, Ctra Colmenar Viejo,Km 9,100, Madrid 28034, Spain
Cadiñanos, J:
Fdn Ctr Med Asturias, Jose Maria Richard Grandio S-N, Oviedo 33193, Asturias, Spain
Sánchez-Heras, AB:
Elche Gen Univ Hosp, Med Oncol Dept, Canc Genet Counseling Unit, Almazara 11, Elche 03203, Spain
Bigas, A:
Inst Salud Carlos III, Ctr Invest Biomed Red Canc CIBERONC, Monforte de Lemos 3-5, Madrid 28029, Spain
Inst Hosp del Mar Invest Med, Program Canc Res, Dr Aiguader 88, Barcelona 08003, Spain
Josep Carreras Leukemia Res Inst, Ctra Can Ruti,Cami Escoles,S-N, Barcelona 08916, Spain
Capellá, G:
Inst Invest Biomed Bellvitge IDIBELL ONCOBELL, Catalan Inst Oncol, Hereditary Canc Program, Barcelona 08908, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Canc CIBERONC, Monforte de Lemos 3-5, Madrid 28029, Spain
Lazaro, C:
Inst Invest Biomed Bellvitge IDIBELL ONCOBELL, Catalan Inst Oncol, Hereditary Canc Program, Barcelona 08908, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Canc CIBERONC, Monforte de Lemos 3-5, Madrid 28029, Spain
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