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Clinical Exome Studies Have Inconsistent Coverage
Abstract BACKGROUND Exome sequencing has become a commonly used clinical diagnostic test. Multiple studies have examined the diagnostic utility and individual laboratory performance of exome testing; however, no previous study has surveyed and compared the data quality from multiple clinical laborat...
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| Published in: | Clinical chemistry (Baltimore, Md.) Md.), 2020-01, Vol.66 (1), p.199-206 |
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| container_end_page | 206 |
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| container_title | Clinical chemistry (Baltimore, Md.) |
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| creator | Gotway, Garrett Crossley, Eric Kozlitina, Julia Xing, Chao Fan, Judy Hornbuckle, Callie Thies, Jenny Michel, Donnice Quinn, Christine Scheuerle, Angela E Umana, Luis A Uhles, Crescenda L Park, Jason Y |
| description | Abstract
BACKGROUND
Exome sequencing has become a commonly used clinical diagnostic test. Multiple studies have examined the diagnostic utility and individual laboratory performance of exome testing; however, no previous study has surveyed and compared the data quality from multiple clinical laboratories.
METHODS
We examined sequencing data from 36 clinical exome tests from 3 clinical laboratories. Exome data were compared in terms of overall characteristics and coverage of specific genes and nucleotide positions. The sets of genes examined included genes in Consensus Coding Sequence (CCDS) (n = 17723), a subset of genes clinically relevant to epilepsy (n = 108), and genes that are recommended for reporting of secondary findings (n = 57; excludes X-linked genes).
RESULTS
The average exome nucleotide coverage (≥20×) of each laboratory varied at 96.49% (CV = 3%), 96.54% (CV = 1%), and 91.68% (CV = 4%), for laboratories A, B, and C, respectively. For CCDS genes, the average number of completely covered genes varied at 12184 (CV = 29%), 11687 (CV = 13%), and 5989 (CV = 37%), for laboratories A, B, and C, respectively. With smaller subsets of genes related to epilepsy and secondary findings, the CV revealed low consistency, with a maximum CV seen in laboratory C for both epilepsy genes (CV = 60%) and secondary findings genes (CV = 71%).
CONCLUSIONS
Poor consistency in complete gene coverage was seen in the clinical exome laboratories surveyed. The degree of consistency varied widely between the laboratories. |
| doi_str_mv | 10.1093/clinchem.2019.306795 |
| format | article |
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BACKGROUND
Exome sequencing has become a commonly used clinical diagnostic test. Multiple studies have examined the diagnostic utility and individual laboratory performance of exome testing; however, no previous study has surveyed and compared the data quality from multiple clinical laboratories.
METHODS
We examined sequencing data from 36 clinical exome tests from 3 clinical laboratories. Exome data were compared in terms of overall characteristics and coverage of specific genes and nucleotide positions. The sets of genes examined included genes in Consensus Coding Sequence (CCDS) (n = 17723), a subset of genes clinically relevant to epilepsy (n = 108), and genes that are recommended for reporting of secondary findings (n = 57; excludes X-linked genes).
RESULTS
The average exome nucleotide coverage (≥20×) of each laboratory varied at 96.49% (CV = 3%), 96.54% (CV = 1%), and 91.68% (CV = 4%), for laboratories A, B, and C, respectively. For CCDS genes, the average number of completely covered genes varied at 12184 (CV = 29%), 11687 (CV = 13%), and 5989 (CV = 37%), for laboratories A, B, and C, respectively. With smaller subsets of genes related to epilepsy and secondary findings, the CV revealed low consistency, with a maximum CV seen in laboratory C for both epilepsy genes (CV = 60%) and secondary findings genes (CV = 71%).
CONCLUSIONS
Poor consistency in complete gene coverage was seen in the clinical exome laboratories surveyed. The degree of consistency varied widely between the laboratories.</description><identifier>ISSN: 0009-9147</identifier><identifier>EISSN: 1530-8561</identifier><identifier>DOI: 10.1093/clinchem.2019.306795</identifier><language>eng</language><publisher>Washington: American Association for Clinical Chemistry, Inc</publisher><subject>Chromosomes ; Comparative analysis ; Conserved sequence ; Consistency ; Datasets ; Diagnostic equipment (Medical) ; Diagnostic systems ; Epilepsy ; Genes ; Genomes ; Information management ; Laboratories ; Medical laboratories ; Nucleotides ; Studies ; Surveys</subject><ispartof>Clinical chemistry (Baltimore, Md.), 2020-01, Vol.66 (1), p.199-206</ispartof><rights>COPYRIGHT 2020 American Association for Clinical Chemistry, Inc.</rights><rights>Copyright American Association for Clinical Chemistry Jan 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c392t-91bede35327cc0243bddcb6d5d7bdd6a8d4352ae0587ab20fb9ac8515b74fcd23</citedby><cites>FETCH-LOGICAL-c392t-91bede35327cc0243bddcb6d5d7bdd6a8d4352ae0587ab20fb9ac8515b74fcd23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids></links><search><creatorcontrib>Gotway, Garrett</creatorcontrib><creatorcontrib>Crossley, Eric</creatorcontrib><creatorcontrib>Kozlitina, Julia</creatorcontrib><creatorcontrib>Xing, Chao</creatorcontrib><creatorcontrib>Fan, Judy</creatorcontrib><creatorcontrib>Hornbuckle, Callie</creatorcontrib><creatorcontrib>Thies, Jenny</creatorcontrib><creatorcontrib>Michel, Donnice</creatorcontrib><creatorcontrib>Quinn, Christine</creatorcontrib><creatorcontrib>Scheuerle, Angela E</creatorcontrib><creatorcontrib>Umana, Luis A</creatorcontrib><creatorcontrib>Uhles, Crescenda L</creatorcontrib><creatorcontrib>Park, Jason Y</creatorcontrib><title>Clinical Exome Studies Have Inconsistent Coverage</title><title>Clinical chemistry (Baltimore, Md.)</title><description>Abstract
BACKGROUND
Exome sequencing has become a commonly used clinical diagnostic test. Multiple studies have examined the diagnostic utility and individual laboratory performance of exome testing; however, no previous study has surveyed and compared the data quality from multiple clinical laboratories.
METHODS
We examined sequencing data from 36 clinical exome tests from 3 clinical laboratories. Exome data were compared in terms of overall characteristics and coverage of specific genes and nucleotide positions. The sets of genes examined included genes in Consensus Coding Sequence (CCDS) (n = 17723), a subset of genes clinically relevant to epilepsy (n = 108), and genes that are recommended for reporting of secondary findings (n = 57; excludes X-linked genes).
RESULTS
The average exome nucleotide coverage (≥20×) of each laboratory varied at 96.49% (CV = 3%), 96.54% (CV = 1%), and 91.68% (CV = 4%), for laboratories A, B, and C, respectively. For CCDS genes, the average number of completely covered genes varied at 12184 (CV = 29%), 11687 (CV = 13%), and 5989 (CV = 37%), for laboratories A, B, and C, respectively. With smaller subsets of genes related to epilepsy and secondary findings, the CV revealed low consistency, with a maximum CV seen in laboratory C for both epilepsy genes (CV = 60%) and secondary findings genes (CV = 71%).
CONCLUSIONS
Poor consistency in complete gene coverage was seen in the clinical exome laboratories surveyed. The degree of consistency varied widely between the laboratories.</description><subject>Chromosomes</subject><subject>Comparative analysis</subject><subject>Conserved sequence</subject><subject>Consistency</subject><subject>Datasets</subject><subject>Diagnostic equipment (Medical)</subject><subject>Diagnostic systems</subject><subject>Epilepsy</subject><subject>Genes</subject><subject>Genomes</subject><subject>Information management</subject><subject>Laboratories</subject><subject>Medical laboratories</subject><subject>Nucleotides</subject><subject>Studies</subject><subject>Surveys</subject><issn>0009-9147</issn><issn>1530-8561</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNpdkEtLw0AQgBdRsFb_gYeAFz2k7jObPZbQ2kJBsHpeNruTmpJHzSal_nu3RC-eZga-eX0I3RM8I1ixZ1uVjf2EekYxUTOGE6nEBZoQwXCcioRcognGWMWKcHmNbrzfh5LLNJkgkoXe0poqWpzaGqJtP7gSfLQyR4jWjW0bX_oemj7K2iN0Zge36KowlYe73zhFH8vFe7aKN68v62y-iS1TtA-7cnDABKPSWkw5y52zeeKEkyFLTOo4E9QAFqk0OcVFroxNBRG55IV1lE3R4zj30LVfA_he16W3UFWmgXbwmnKiJBEkfDlFD__QfTt0TbhOUyY4Z5LyNFBPI7UzFejy_FsPp35nBu_1evum5wkLB5BgLLB8ZG3Xet9BoQ9dWZvuWxOsz871n3N9dq5H5-wHX0J1YA</recordid><startdate>20200101</startdate><enddate>20200101</enddate><creator>Gotway, Garrett</creator><creator>Crossley, Eric</creator><creator>Kozlitina, Julia</creator><creator>Xing, Chao</creator><creator>Fan, Judy</creator><creator>Hornbuckle, Callie</creator><creator>Thies, Jenny</creator><creator>Michel, Donnice</creator><creator>Quinn, Christine</creator><creator>Scheuerle, Angela E</creator><creator>Umana, Luis A</creator><creator>Uhles, Crescenda L</creator><creator>Park, Jason Y</creator><general>American Association for Clinical Chemistry, Inc</general><general>Oxford University 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Exome Studies Have Inconsistent Coverage</title><author>Gotway, Garrett ; Crossley, Eric ; Kozlitina, Julia ; Xing, Chao ; Fan, Judy ; Hornbuckle, Callie ; Thies, Jenny ; Michel, Donnice ; Quinn, Christine ; Scheuerle, Angela E ; Umana, Luis A ; Uhles, Crescenda L ; Park, Jason Y</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c392t-91bede35327cc0243bddcb6d5d7bdd6a8d4352ae0587ab20fb9ac8515b74fcd23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Chromosomes</topic><topic>Comparative analysis</topic><topic>Conserved sequence</topic><topic>Consistency</topic><topic>Datasets</topic><topic>Diagnostic equipment (Medical)</topic><topic>Diagnostic systems</topic><topic>Epilepsy</topic><topic>Genes</topic><topic>Genomes</topic><topic>Information management</topic><topic>Laboratories</topic><topic>Medical 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Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gotway, Garrett</au><au>Crossley, Eric</au><au>Kozlitina, Julia</au><au>Xing, Chao</au><au>Fan, Judy</au><au>Hornbuckle, Callie</au><au>Thies, Jenny</au><au>Michel, Donnice</au><au>Quinn, Christine</au><au>Scheuerle, Angela E</au><au>Umana, Luis A</au><au>Uhles, Crescenda L</au><au>Park, Jason Y</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinical Exome Studies Have Inconsistent Coverage</atitle><jtitle>Clinical chemistry (Baltimore, Md.)</jtitle><date>2020-01-01</date><risdate>2020</risdate><volume>66</volume><issue>1</issue><spage>199</spage><epage>206</epage><pages>199-206</pages><issn>0009-9147</issn><eissn>1530-8561</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Abstract
BACKGROUND
Exome sequencing has become a commonly used clinical diagnostic test. Multiple studies have examined the diagnostic utility and individual laboratory performance of exome testing; however, no previous study has surveyed and compared the data quality from multiple clinical laboratories.
METHODS
We examined sequencing data from 36 clinical exome tests from 3 clinical laboratories. Exome data were compared in terms of overall characteristics and coverage of specific genes and nucleotide positions. The sets of genes examined included genes in Consensus Coding Sequence (CCDS) (n = 17723), a subset of genes clinically relevant to epilepsy (n = 108), and genes that are recommended for reporting of secondary findings (n = 57; excludes X-linked genes).
RESULTS
The average exome nucleotide coverage (≥20×) of each laboratory varied at 96.49% (CV = 3%), 96.54% (CV = 1%), and 91.68% (CV = 4%), for laboratories A, B, and C, respectively. For CCDS genes, the average number of completely covered genes varied at 12184 (CV = 29%), 11687 (CV = 13%), and 5989 (CV = 37%), for laboratories A, B, and C, respectively. With smaller subsets of genes related to epilepsy and secondary findings, the CV revealed low consistency, with a maximum CV seen in laboratory C for both epilepsy genes (CV = 60%) and secondary findings genes (CV = 71%).
CONCLUSIONS
Poor consistency in complete gene coverage was seen in the clinical exome laboratories surveyed. The degree of consistency varied widely between the laboratories.</abstract><cop>Washington</cop><pub>American Association for Clinical Chemistry, Inc</pub><doi>10.1093/clinchem.2019.306795</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0009-9147 |
| ispartof | Clinical chemistry (Baltimore, Md.), 2020-01, Vol.66 (1), p.199-206 |
| issn | 0009-9147 1530-8561 |
| language | eng |
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| source | Oxford University Press Journals All Titles (1996-Current) |
| subjects | Chromosomes Comparative analysis Conserved sequence Consistency Datasets Diagnostic equipment (Medical) Diagnostic systems Epilepsy Genes Genomes Information management Laboratories Medical laboratories Nucleotides Studies Surveys |
| title | Clinical Exome Studies Have Inconsistent Coverage |
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