Proteomics and Down syndrome screening: a validation study
Objective In a previous discovery study, we identified seven potential screening markers for Down syndrome (DS). Here, we report on an extended study to validate the discriminative potential of these markers. Methods Concentrations of the seven analytes were measured using bead‐based multiplexed imm...
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Veröffentlicht in: | Prenatal diagnosis 2010-11, Vol.30 (11), p.1039-1043 |
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creator | Koster, M. P. H. Pennings, J. L. A. Imholz, S. Rodenburg, W. Visser, G. H. A. de Vries, A. Schielen, P. C. J. I. |
description | Objective
In a previous discovery study, we identified seven potential screening markers for Down syndrome (DS). Here, we report on an extended study to validate the discriminative potential of these markers.
Methods
Concentrations of the seven analytes were measured using bead‐based multiplexed immunoassays in maternal serum from 27 DS pregnancies and 27 matched controls. Control samples were matched to the cases by gestational age (exact day), maternal weight ( ± 5 kg), and maternal age ( ± 1 year) and by closest sample date. Prediction values were obtained for current screening markers [pregnancy‐associated plasma protein A (PAPP‐A), free beta human chorionic gonadotrophin (fβ‐hCG) and nuchal translucency (NT)] and seven markers identified before based on concentration fold ratios between DS and controls. Models were fitted based on data of the discovery study or this study and also tested on both datasets.
Results
A significantly higher fold ratio was only found for epidermal growth factor (EGF) (−1.96; p = 0.006). In the prediction model for the current dataset, EGF improved the detection rate (DR) of DS by 5.7% [at a fixed 5% false‐positive rate (FPR)] when added to the currently used screening markers.
Conclusions
Validation of previously identified biomarkers only confirmed EGF for further consideration as a DS screening marker. This underlines the importance of validating biomarkers; in this study, limiting the range of plausible biomarkers to only one suitable biomarker. Copyright © 2010 John Wiley & Sons, Ltd. |
doi_str_mv | 10.1002/pd.2606 |
format | Article |
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In a previous discovery study, we identified seven potential screening markers for Down syndrome (DS). Here, we report on an extended study to validate the discriminative potential of these markers.
Methods
Concentrations of the seven analytes were measured using bead‐based multiplexed immunoassays in maternal serum from 27 DS pregnancies and 27 matched controls. Control samples were matched to the cases by gestational age (exact day), maternal weight ( ± 5 kg), and maternal age ( ± 1 year) and by closest sample date. Prediction values were obtained for current screening markers [pregnancy‐associated plasma protein A (PAPP‐A), free beta human chorionic gonadotrophin (fβ‐hCG) and nuchal translucency (NT)] and seven markers identified before based on concentration fold ratios between DS and controls. Models were fitted based on data of the discovery study or this study and also tested on both datasets.
Results
A significantly higher fold ratio was only found for epidermal growth factor (EGF) (−1.96; p = 0.006). In the prediction model for the current dataset, EGF improved the detection rate (DR) of DS by 5.7% [at a fixed 5% false‐positive rate (FPR)] when added to the currently used screening markers.
Conclusions
Validation of previously identified biomarkers only confirmed EGF for further consideration as a DS screening marker. This underlines the importance of validating biomarkers; in this study, limiting the range of plausible biomarkers to only one suitable biomarker. Copyright © 2010 John Wiley & Sons, Ltd.</description><identifier>ISSN: 0197-3851</identifier><identifier>EISSN: 1097-0223</identifier><identifier>DOI: 10.1002/pd.2606</identifier><identifier>PMID: 20827711</identifier><identifier>CODEN: PRDIDM</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Adult ; bead-based multiplexed assays ; Biological and medical sciences ; biomarkers ; Biomarkers - blood ; Case-Control Studies ; Delivery. Postpartum. Lactation ; Down syndrome ; Down Syndrome - blood ; Down Syndrome - diagnostic imaging ; epidermal growth factor (EGF) ; Female ; first-trimester serum screening ; Fundamental and applied biological sciences. Psychology ; Genetics of eukaryotes. Biological and molecular evolution ; Gynecology. Andrology. Obstetrics ; Humans ; Infant, Newborn ; Medical sciences ; Molecular and cellular biology ; Predictive Value of Tests ; Pregnancy ; Pregnancy Trimester, First ; Prenatal Diagnosis - methods ; Prenatal Diagnosis - standards ; Proteomics - methods ; Proteomics - standards ; Reproducibility of Results ; Retrospective Studies ; Sensitivity and Specificity ; Ultrasonography</subject><ispartof>Prenatal diagnosis, 2010-11, Vol.30 (11), p.1039-1043</ispartof><rights>Copyright © 2010 John Wiley & Sons, Ltd.</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3846-98ee7f3958ca42b85404dc863df633e4304b2c8f7af9f2d1189ff488288ce97c3</citedby><cites>FETCH-LOGICAL-c3846-98ee7f3958ca42b85404dc863df633e4304b2c8f7af9f2d1189ff488288ce97c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpd.2606$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpd.2606$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23356148$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20827711$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Koster, M. P. H.</creatorcontrib><creatorcontrib>Pennings, J. L. A.</creatorcontrib><creatorcontrib>Imholz, S.</creatorcontrib><creatorcontrib>Rodenburg, W.</creatorcontrib><creatorcontrib>Visser, G. H. A.</creatorcontrib><creatorcontrib>de Vries, A.</creatorcontrib><creatorcontrib>Schielen, P. C. J. I.</creatorcontrib><title>Proteomics and Down syndrome screening: a validation study</title><title>Prenatal diagnosis</title><addtitle>Prenat. Diagn</addtitle><description>Objective
In a previous discovery study, we identified seven potential screening markers for Down syndrome (DS). Here, we report on an extended study to validate the discriminative potential of these markers.
Methods
Concentrations of the seven analytes were measured using bead‐based multiplexed immunoassays in maternal serum from 27 DS pregnancies and 27 matched controls. Control samples were matched to the cases by gestational age (exact day), maternal weight ( ± 5 kg), and maternal age ( ± 1 year) and by closest sample date. Prediction values were obtained for current screening markers [pregnancy‐associated plasma protein A (PAPP‐A), free beta human chorionic gonadotrophin (fβ‐hCG) and nuchal translucency (NT)] and seven markers identified before based on concentration fold ratios between DS and controls. Models were fitted based on data of the discovery study or this study and also tested on both datasets.
Results
A significantly higher fold ratio was only found for epidermal growth factor (EGF) (−1.96; p = 0.006). In the prediction model for the current dataset, EGF improved the detection rate (DR) of DS by 5.7% [at a fixed 5% false‐positive rate (FPR)] when added to the currently used screening markers.
Conclusions
Validation of previously identified biomarkers only confirmed EGF for further consideration as a DS screening marker. This underlines the importance of validating biomarkers; in this study, limiting the range of plausible biomarkers to only one suitable biomarker. Copyright © 2010 John Wiley & Sons, Ltd.</description><subject>Adult</subject><subject>bead-based multiplexed assays</subject><subject>Biological and medical sciences</subject><subject>biomarkers</subject><subject>Biomarkers - blood</subject><subject>Case-Control Studies</subject><subject>Delivery. Postpartum. Lactation</subject><subject>Down syndrome</subject><subject>Down Syndrome - blood</subject><subject>Down Syndrome - diagnostic imaging</subject><subject>epidermal growth factor (EGF)</subject><subject>Female</subject><subject>first-trimester serum screening</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Infant, Newborn</subject><subject>Medical sciences</subject><subject>Molecular and cellular biology</subject><subject>Predictive Value of Tests</subject><subject>Pregnancy</subject><subject>Pregnancy Trimester, First</subject><subject>Prenatal Diagnosis - methods</subject><subject>Prenatal Diagnosis - standards</subject><subject>Proteomics - methods</subject><subject>Proteomics - standards</subject><subject>Reproducibility of Results</subject><subject>Retrospective Studies</subject><subject>Sensitivity and Specificity</subject><subject>Ultrasonography</subject><issn>0197-3851</issn><issn>1097-0223</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10ElLAzEYBuAgiq0L_gOZi3iQ0WyTZHoTta1QF1zoMaRZJDpLTabW_ntHWtuTp-87PLwvvAAcIXiOIMQXU3OOGWRboItgzlOIMdkGXYjan4gMdcBejO8tFDjnu6CDocCcI9QFvcdQN7YuvY6JqkxyXc-rJC4qE-rSJlEHaytfvfUSlXypwhvV-LoFzcwsDsCOU0W0h6u7D177Ny9Xw3T0MLi9uhylmgjK0lxYyx3JM6EVxRORUUiNFowYxwixlEA6wVo4rlzusEFI5M5RIbAQ2uZck31wusydhvpzZmMjSx-1LQpV2XoWJWeYcsSzfCN1qGMM1slp8KUKC4mg_N1JTo383amVx6vM2aS0Zu3-hmnByQqoqFXhgqq0jxtHSMYQFa07W7q5L-zivz75eL2qTZfax8Z-r7UKH5JxwjM5vh9I1h-T4dPznaTkB5-3iwM</recordid><startdate>201011</startdate><enddate>201011</enddate><creator>Koster, M. P. H.</creator><creator>Pennings, J. L. A.</creator><creator>Imholz, S.</creator><creator>Rodenburg, W.</creator><creator>Visser, G. H. A.</creator><creator>de Vries, A.</creator><creator>Schielen, P. C. J. I.</creator><general>John Wiley & Sons, Ltd</general><general>Wiley</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201011</creationdate><title>Proteomics and Down syndrome screening: a validation study</title><author>Koster, M. P. H. ; Pennings, J. L. A. ; Imholz, S. ; Rodenburg, W. ; Visser, G. H. A. ; de Vries, A. ; Schielen, P. C. J. I.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3846-98ee7f3958ca42b85404dc863df633e4304b2c8f7af9f2d1189ff488288ce97c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adult</topic><topic>bead-based multiplexed assays</topic><topic>Biological and medical sciences</topic><topic>biomarkers</topic><topic>Biomarkers - blood</topic><topic>Case-Control Studies</topic><topic>Delivery. Postpartum. Lactation</topic><topic>Down syndrome</topic><topic>Down Syndrome - blood</topic><topic>Down Syndrome - diagnostic imaging</topic><topic>epidermal growth factor (EGF)</topic><topic>Female</topic><topic>first-trimester serum screening</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genetics of eukaryotes. Biological and molecular evolution</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Infant, Newborn</topic><topic>Medical sciences</topic><topic>Molecular and cellular biology</topic><topic>Predictive Value of Tests</topic><topic>Pregnancy</topic><topic>Pregnancy Trimester, First</topic><topic>Prenatal Diagnosis - methods</topic><topic>Prenatal Diagnosis - standards</topic><topic>Proteomics - methods</topic><topic>Proteomics - standards</topic><topic>Reproducibility of Results</topic><topic>Retrospective Studies</topic><topic>Sensitivity and Specificity</topic><topic>Ultrasonography</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Koster, M. P. H.</creatorcontrib><creatorcontrib>Pennings, J. L. A.</creatorcontrib><creatorcontrib>Imholz, S.</creatorcontrib><creatorcontrib>Rodenburg, W.</creatorcontrib><creatorcontrib>Visser, G. H. A.</creatorcontrib><creatorcontrib>de Vries, A.</creatorcontrib><creatorcontrib>Schielen, P. C. J. I.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Prenatal diagnosis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Koster, M. P. H.</au><au>Pennings, J. L. A.</au><au>Imholz, S.</au><au>Rodenburg, W.</au><au>Visser, G. H. A.</au><au>de Vries, A.</au><au>Schielen, P. C. J. I.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Proteomics and Down syndrome screening: a validation study</atitle><jtitle>Prenatal diagnosis</jtitle><addtitle>Prenat. Diagn</addtitle><date>2010-11</date><risdate>2010</risdate><volume>30</volume><issue>11</issue><spage>1039</spage><epage>1043</epage><pages>1039-1043</pages><issn>0197-3851</issn><eissn>1097-0223</eissn><coden>PRDIDM</coden><abstract>Objective
In a previous discovery study, we identified seven potential screening markers for Down syndrome (DS). Here, we report on an extended study to validate the discriminative potential of these markers.
Methods
Concentrations of the seven analytes were measured using bead‐based multiplexed immunoassays in maternal serum from 27 DS pregnancies and 27 matched controls. Control samples were matched to the cases by gestational age (exact day), maternal weight ( ± 5 kg), and maternal age ( ± 1 year) and by closest sample date. Prediction values were obtained for current screening markers [pregnancy‐associated plasma protein A (PAPP‐A), free beta human chorionic gonadotrophin (fβ‐hCG) and nuchal translucency (NT)] and seven markers identified before based on concentration fold ratios between DS and controls. Models were fitted based on data of the discovery study or this study and also tested on both datasets.
Results
A significantly higher fold ratio was only found for epidermal growth factor (EGF) (−1.96; p = 0.006). In the prediction model for the current dataset, EGF improved the detection rate (DR) of DS by 5.7% [at a fixed 5% false‐positive rate (FPR)] when added to the currently used screening markers.
Conclusions
Validation of previously identified biomarkers only confirmed EGF for further consideration as a DS screening marker. This underlines the importance of validating biomarkers; in this study, limiting the range of plausible biomarkers to only one suitable biomarker. Copyright © 2010 John Wiley & Sons, Ltd.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>20827711</pmid><doi>10.1002/pd.2606</doi><tpages>5</tpages></addata></record> |
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subjects | Adult bead-based multiplexed assays Biological and medical sciences biomarkers Biomarkers - blood Case-Control Studies Delivery. Postpartum. Lactation Down syndrome Down Syndrome - blood Down Syndrome - diagnostic imaging epidermal growth factor (EGF) Female first-trimester serum screening Fundamental and applied biological sciences. Psychology Genetics of eukaryotes. Biological and molecular evolution Gynecology. Andrology. Obstetrics Humans Infant, Newborn Medical sciences Molecular and cellular biology Predictive Value of Tests Pregnancy Pregnancy Trimester, First Prenatal Diagnosis - methods Prenatal Diagnosis - standards Proteomics - methods Proteomics - standards Reproducibility of Results Retrospective Studies Sensitivity and Specificity Ultrasonography |
title | Proteomics and Down syndrome screening: a validation study |
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