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Quality of whole genome sequencing from blood versus saliva derived DNA in cardiac patients

BACKGROUND: Whole-genome sequencing (WGS) is becoming an increasingly important tool for detecting genomic variation. Blood derived DNA is the current standard for WGS for research or clinical purposes but may not always be feasible to acquire. The usability of DNA from saliva for WGS is not known....

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Detalles Bibliográficos
Autores principales: Yao, Roderick A., Akinrinade, Oyediran, Chaix, Marie, Mital, Seema
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988365/
https://www.ncbi.nlm.nih.gov/pubmed/31996208
http://dx.doi.org/10.1186/s12920-020-0664-7
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author Yao, Roderick A.
Akinrinade, Oyediran
Chaix, Marie
Mital, Seema
author_facet Yao, Roderick A.
Akinrinade, Oyediran
Chaix, Marie
Mital, Seema
author_sort Yao, Roderick A.
collection PubMed
description BACKGROUND: Whole-genome sequencing (WGS) is becoming an increasingly important tool for detecting genomic variation. Blood derived DNA is the current standard for WGS for research or clinical purposes but may not always be feasible to acquire. The usability of DNA from saliva for WGS is not known. We compared the quality of WGS between blood versus saliva derived DNA. METHODS: WGS was performed in DNA from 531 blood and 502 saliva samples (including 5 paired samples) from participants enrolled in a heart disease biorepository. We compared the proportion of sequencing reads that mapped to non-human sources (microbiome), the sequencing coverage, and the yield and concordance of single nucleotide variant (SNV) and copy number variant (CNV) calls between blood and saliva genomes. RESULTS: Of 531 blood and 502 saliva samples, 46% saliva DNA failed quality control (QC) requirements for WGS compared to 6% QC failure for blood DNA. An average of 10.7% WGS reads in the saliva samples mapped to the human oral microbiome compared to 0.09% WGS reads in blood samples. However, these reads were readily excluded by excluding reads that did not map to the human reference genome. Sequencing coverage met or exceeded the target sequencing depth of 30x in all the blood samples and 4 of the 5 saliva samples; the fifth saliva sample had an average sequencing depth of 22.6x. Over 95% of SNVs identified in saliva were concordant with those identified in blood across the genome, within all gene coding regions, and within cardiovascular disease-related gene coding regions. Rare SNVs, defined as those with a minor allele frequency of less than 1% in the Genome Aggregation Database, had a lower concordance of 90% between blood and saliva genomes. CNVs had only 76% concordance between blood and saliva samples. CONCLUSIONS: High quality saliva samples that meet stringent QC criteria can be used for WGS when blood-derived DNA is not available or is not suitable. Saliva DNA provides an acceptable yield of SNV calls but has a lower yield for CNV calls compared to blood DNA.
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spelling pubmed-69883652020-02-03 Quality of whole genome sequencing from blood versus saliva derived DNA in cardiac patients Yao, Roderick A. Akinrinade, Oyediran Chaix, Marie Mital, Seema BMC Med Genomics Research Article BACKGROUND: Whole-genome sequencing (WGS) is becoming an increasingly important tool for detecting genomic variation. Blood derived DNA is the current standard for WGS for research or clinical purposes but may not always be feasible to acquire. The usability of DNA from saliva for WGS is not known. We compared the quality of WGS between blood versus saliva derived DNA. METHODS: WGS was performed in DNA from 531 blood and 502 saliva samples (including 5 paired samples) from participants enrolled in a heart disease biorepository. We compared the proportion of sequencing reads that mapped to non-human sources (microbiome), the sequencing coverage, and the yield and concordance of single nucleotide variant (SNV) and copy number variant (CNV) calls between blood and saliva genomes. RESULTS: Of 531 blood and 502 saliva samples, 46% saliva DNA failed quality control (QC) requirements for WGS compared to 6% QC failure for blood DNA. An average of 10.7% WGS reads in the saliva samples mapped to the human oral microbiome compared to 0.09% WGS reads in blood samples. However, these reads were readily excluded by excluding reads that did not map to the human reference genome. Sequencing coverage met or exceeded the target sequencing depth of 30x in all the blood samples and 4 of the 5 saliva samples; the fifth saliva sample had an average sequencing depth of 22.6x. Over 95% of SNVs identified in saliva were concordant with those identified in blood across the genome, within all gene coding regions, and within cardiovascular disease-related gene coding regions. Rare SNVs, defined as those with a minor allele frequency of less than 1% in the Genome Aggregation Database, had a lower concordance of 90% between blood and saliva genomes. CNVs had only 76% concordance between blood and saliva samples. CONCLUSIONS: High quality saliva samples that meet stringent QC criteria can be used for WGS when blood-derived DNA is not available or is not suitable. Saliva DNA provides an acceptable yield of SNV calls but has a lower yield for CNV calls compared to blood DNA. BioMed Central 2020-01-29 /pmc/articles/PMC6988365/ /pubmed/31996208 http://dx.doi.org/10.1186/s12920-020-0664-7 Text en © The Author(s). 2020 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Yao, Roderick A.
Akinrinade, Oyediran
Chaix, Marie
Mital, Seema
Quality of whole genome sequencing from blood versus saliva derived DNA in cardiac patients
title Quality of whole genome sequencing from blood versus saliva derived DNA in cardiac patients
title_full Quality of whole genome sequencing from blood versus saliva derived DNA in cardiac patients
title_fullStr Quality of whole genome sequencing from blood versus saliva derived DNA in cardiac patients
title_full_unstemmed Quality of whole genome sequencing from blood versus saliva derived DNA in cardiac patients
title_short Quality of whole genome sequencing from blood versus saliva derived DNA in cardiac patients
title_sort quality of whole genome sequencing from blood versus saliva derived dna in cardiac patients
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988365/
https://www.ncbi.nlm.nih.gov/pubmed/31996208
http://dx.doi.org/10.1186/s12920-020-0664-7
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