The Brazilian Rare Genomes Project: Validation of Whole Genome Sequencing for Rare Diseases Diagnosis
Rare diseases affect up to 13.2 million individuals in Brazil. The Brazilian Rare Genomes Project is envisioned to further the implementation of genomic medicine into the Brazilian public healthcare system. Here we report the validation results of a whole genome sequencing (WGS) procedure for implem...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2022.821582/full |
| _version_ | 1828365682399510528 |
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| author | Antonio Victor Campos Coelho Bruna Mascaro-Cordeiro Danielle Ribeiro Lucon Maria Soares Nóbrega Rodrigo de Souza Reis Rodrigo Bertollo de Alexandre Livia Maria Silva Moura Gustavo Santos de Oliveira Rafael Lucas Muniz Guedes Marcel Pinheiro Caraciolo Nuria Bengala Zurro Murilo Castro Cervato João Bosco Oliveira |
| author_facet | Antonio Victor Campos Coelho Bruna Mascaro-Cordeiro Danielle Ribeiro Lucon Maria Soares Nóbrega Rodrigo de Souza Reis Rodrigo Bertollo de Alexandre Livia Maria Silva Moura Gustavo Santos de Oliveira Rafael Lucas Muniz Guedes Marcel Pinheiro Caraciolo Nuria Bengala Zurro Murilo Castro Cervato João Bosco Oliveira |
| author_sort | Antonio Victor Campos Coelho |
| collection | DOAJ |
| description | Rare diseases affect up to 13.2 million individuals in Brazil. The Brazilian Rare Genomes Project is envisioned to further the implementation of genomic medicine into the Brazilian public healthcare system. Here we report the validation results of a whole genome sequencing (WGS) procedure for implementation in clinical laboratories. In addition, we report data quality for the first 1,200 real-world patients sequenced. We sequenced a well-characterized group of 76 samples, including seven gold standard genomes, using a PCR-free WGS protocol on Illumina Novaseq 6,000 equipment. We compared the observed variant calls with their expected calls, observing good concordance for single nucleotide variants (SNVs; mean F-measure = 99.82%) and indels (mean F-measure = 99.57%). Copy number variants and structural variants events detection performances were as expected (F-measures 96.6% and 90.3%, respectively). Our WGS protocol presented excellent intra-assay reproducibility (coefficients of variation ranging between 0.03% and 0.20%) and inter-assay reproducibility (coefficients of variation ranging between 0.02% and 0.09%). Limitations of the WGS protocol include the inability to confidently detect variants such as uniparental disomy, balanced translocations, repeat expansion variants, and low-level mosaicism. In summary, the observed performance of the WGS protocol was in accordance with that seen in the best centers worldwide. The Rare Genomes Project is an important initiative to bring pivotal improvements to the quality of life of the affected individuals. |
| first_indexed | 2024-04-14T05:34:12Z |
| format | Article |
| id | doaj.art-e5119c6c2b3948508f5dfa34f830ae7b |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-04-14T05:34:12Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-e5119c6c2b3948508f5dfa34f830ae7b2022-12-22T02:09:42ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2022-05-01910.3389/fmolb.2022.821582821582The Brazilian Rare Genomes Project: Validation of Whole Genome Sequencing for Rare Diseases DiagnosisAntonio Victor Campos CoelhoBruna Mascaro-CordeiroDanielle Ribeiro LuconMaria Soares NóbregaRodrigo de Souza ReisRodrigo Bertollo de AlexandreLivia Maria Silva MouraGustavo Santos de OliveiraRafael Lucas Muniz GuedesMarcel Pinheiro CaracioloNuria Bengala ZurroMurilo Castro CervatoJoão Bosco OliveiraRare diseases affect up to 13.2 million individuals in Brazil. The Brazilian Rare Genomes Project is envisioned to further the implementation of genomic medicine into the Brazilian public healthcare system. Here we report the validation results of a whole genome sequencing (WGS) procedure for implementation in clinical laboratories. In addition, we report data quality for the first 1,200 real-world patients sequenced. We sequenced a well-characterized group of 76 samples, including seven gold standard genomes, using a PCR-free WGS protocol on Illumina Novaseq 6,000 equipment. We compared the observed variant calls with their expected calls, observing good concordance for single nucleotide variants (SNVs; mean F-measure = 99.82%) and indels (mean F-measure = 99.57%). Copy number variants and structural variants events detection performances were as expected (F-measures 96.6% and 90.3%, respectively). Our WGS protocol presented excellent intra-assay reproducibility (coefficients of variation ranging between 0.03% and 0.20%) and inter-assay reproducibility (coefficients of variation ranging between 0.02% and 0.09%). Limitations of the WGS protocol include the inability to confidently detect variants such as uniparental disomy, balanced translocations, repeat expansion variants, and low-level mosaicism. In summary, the observed performance of the WGS protocol was in accordance with that seen in the best centers worldwide. The Rare Genomes Project is an important initiative to bring pivotal improvements to the quality of life of the affected individuals.https://www.frontiersin.org/articles/10.3389/fmolb.2022.821582/fullrare diseasesprecision medicinegenomicsgenetic diagnostic testwhole genome sequencing |
| spellingShingle | Antonio Victor Campos Coelho Bruna Mascaro-Cordeiro Danielle Ribeiro Lucon Maria Soares Nóbrega Rodrigo de Souza Reis Rodrigo Bertollo de Alexandre Livia Maria Silva Moura Gustavo Santos de Oliveira Rafael Lucas Muniz Guedes Marcel Pinheiro Caraciolo Nuria Bengala Zurro Murilo Castro Cervato João Bosco Oliveira The Brazilian Rare Genomes Project: Validation of Whole Genome Sequencing for Rare Diseases Diagnosis Frontiers in Molecular Biosciences rare diseases precision medicine genomics genetic diagnostic test whole genome sequencing |
| title | The Brazilian Rare Genomes Project: Validation of Whole Genome Sequencing for Rare Diseases Diagnosis |
| title_full | The Brazilian Rare Genomes Project: Validation of Whole Genome Sequencing for Rare Diseases Diagnosis |
| title_fullStr | The Brazilian Rare Genomes Project: Validation of Whole Genome Sequencing for Rare Diseases Diagnosis |
| title_full_unstemmed | The Brazilian Rare Genomes Project: Validation of Whole Genome Sequencing for Rare Diseases Diagnosis |
| title_short | The Brazilian Rare Genomes Project: Validation of Whole Genome Sequencing for Rare Diseases Diagnosis |
| title_sort | brazilian rare genomes project validation of whole genome sequencing for rare diseases diagnosis |
| topic | rare diseases precision medicine genomics genetic diagnostic test whole genome sequencing |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2022.821582/full |
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