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Article: Cross-oncopanel study reveals high sensitivity and accuracy with overall analytical performance depending on genomic regions

TitleCross-oncopanel study reveals high sensitivity and accuracy with overall analytical performance depending on genomic regions
Authors
Gong, BinshengLi, DanKusko, RebeccaNovoradovskaya, NataliaZhang, YifanWang, ShangziPabón-Peña, CarlosZhang, ZhihongLai, KevinCai, WanshiLoCoco, Jennifer S.Best, HunterBhandari, AmbicaBisgin, HalilBlackburn, JamesBlomquist, Thomas M.Deveson, Ira W.Boardman, LisaBurgher, BlakeButler, Daniel J.Chang, Chia JungMarella, NarasimhaChaubey, AlkaChen, TaoChierici, MarcoChin, Christopher R.Close, DevinConroy, JeffreyDuncan, DanielColeman, Jessica CooleyEterovic, Agda KarinaFan, XiaohuiMartín-Arenas, RubénFoox, JonathanFurlanello, CesareGhosal, AbhisekScherer, AndreasGlenn, SeanGuan, MeijianHaag, ChristineHang, XinyiHappe, ScottHennigan, BrittanyMegherbi, Dalila B.Hipp, JenniferHong, HuixiaoHorvath, KyleHu, JianhongSchulze, EgbertHung, Li YuanJarosz, MirnaKerkhof, JenniferKipp, BenjaminKreil, David PhilipMeng, QingchangŁabaj, PawełLapunzina, PabloLi, PengLi, Quan ZhenLi, WeihuaSebra, RobertLi, ZhiguangLiang, YuLiu, ShaoqingLiu, ZhichaoMieczkowski, Piotr A.Ma, CharlesShaknovich, RitaMorrison, TomMuzny, DonnaNing, BaitangParsons, Barbara L.Xiao, WenzhongPaweletz, Cloud P.Pirooznia, MehdiQu, WubinRaymond, AmeliaRindler, PaulRingler, RebeccaShi, QiangSadikovic, BekimShi, TieliuSilla-Castro, Juan CarlosXu, ShibeiSmith, MelissaLópez, Mario SolísSong, PingLader, EricStetson, DanielStrahl, MayaStuart, AlanSupplee, JuliannaSzankasi, PhilippeTan, HaowenYang, MaryTang, Lin yaTao, YonghuiThakkar, ShraddhaThierry-Mieg, DanielleRichmond, Todd A.Thierry-Mieg, JeanThodima, Venkat J.Thomas, DavidTichý, BorisTom, NikolaYing, JianmingGarcia, Elena VallespinVerma, SumanWalker, KimbleyWang, CharlesWang, JunwenMittal, Vinay K.Wang, YexunWen, ZhiningWirta, ValtteriWu, LeihongYip, Shun H.Xiao, ChunlinLiu, Liang ChunZhang, GuangliangZhang, SaZhao, MeiruZheng, YuantingCraig, Daniel J.Zhou, XiaoyanMason, Christopher E.Mercer, TimothyTong, WeidaShi, LemingJones, WendellJohann, Donald J.Xu, JoshuaWilley, James C.Bushel, Pierre R.Crawford, ErinYu, YingXu, ChangChen, GuangchunBurgess, DanielCawley, SimonGiorda, KristinaHaseley, NathanQiu, FujunWilkins, KatherineArib, Hananedel Pozo, AngelaAttwooll, ClaireBabson, KevinBao, LonglongBao, WenjunLucas, Anne Bergstrom
KeywordsAnalytical performance
Molecular diagnostics
Oncopanel sequencing
Precision medicine
Reproducibility
Target enrichment
Issue Date2021
Citation
Genome Biology, 2021, v. 22, n. 1, article no. 109 How to Cite?
AbstractBackground: Targeted sequencing using oncopanels requires comprehensive assessments of accuracy and detection sensitivity to ensure analytical validity. By employing reference materials characterized by the U.S. Food and Drug Administration-led SEquence Quality Control project phase2 (SEQC2) effort, we perform a cross-platform multi-lab evaluation of eight Pan-Cancer panels to assess best practices for oncopanel sequencing. Results: All panels demonstrate high sensitivity across targeted high-confidence coding regions and variant types for the variants previously verified to have variant allele frequency (VAF) in the 5–20% range. Sensitivity is reduced by utilizing VAF thresholds due to inherent variability in VAF measurements. Enforcing a VAF threshold for reporting has a positive impact on reducing false positive calls. Importantly, the false positive rate is found to be significantly higher outside the high-confidence coding regions, resulting in lower reproducibility. Thus, region restriction and VAF thresholds lead to low relative technical variability in estimating promising biomarkers and tumor mutational burden. Conclusion: This comprehensive study provides actionable guidelines for oncopanel sequencing and clear evidence that supports a simplified approach to assess the analytical performance of oncopanels. It will facilitate the rapid implementation, validation, and quality control of oncopanels in clinical use.
Persistent Identifierhttp://hdl.handle.net/10722/324511
ISSN
2012 Impact Factor: 10.288
2023 SCImago Journal Rankings: 7.197
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorGong, Binsheng-
dc.contributor.authorLi, Dan-
dc.contributor.authorKusko, Rebecca-
dc.contributor.authorNovoradovskaya, Natalia-
dc.contributor.authorZhang, Yifan-
dc.contributor.authorWang, Shangzi-
dc.contributor.authorPabón-Peña, Carlos-
dc.contributor.authorZhang, Zhihong-
dc.contributor.authorLai, Kevin-
dc.contributor.authorCai, Wanshi-
dc.contributor.authorLoCoco, Jennifer S.-
dc.contributor.authorBest, Hunter-
dc.contributor.authorBhandari, Ambica-
dc.contributor.authorBisgin, Halil-
dc.contributor.authorBlackburn, James-
dc.contributor.authorBlomquist, Thomas M.-
dc.contributor.authorDeveson, Ira W.-
dc.contributor.authorBoardman, Lisa-
dc.contributor.authorBurgher, Blake-
dc.contributor.authorButler, Daniel J.-
dc.contributor.authorChang, Chia Jung-
dc.contributor.authorMarella, Narasimha-
dc.contributor.authorChaubey, Alka-
dc.contributor.authorChen, Tao-
dc.contributor.authorChierici, Marco-
dc.contributor.authorChin, Christopher R.-
dc.contributor.authorClose, Devin-
dc.contributor.authorConroy, Jeffrey-
dc.contributor.authorDuncan, Daniel-
dc.contributor.authorColeman, Jessica Cooley-
dc.contributor.authorEterovic, Agda Karina-
dc.contributor.authorFan, Xiaohui-
dc.contributor.authorMartín-Arenas, Rubén-
dc.contributor.authorFoox, Jonathan-
dc.contributor.authorFurlanello, Cesare-
dc.contributor.authorGhosal, Abhisek-
dc.contributor.authorScherer, Andreas-
dc.contributor.authorGlenn, Sean-
dc.contributor.authorGuan, Meijian-
dc.contributor.authorHaag, Christine-
dc.contributor.authorHang, Xinyi-
dc.contributor.authorHappe, Scott-
dc.contributor.authorHennigan, Brittany-
dc.contributor.authorMegherbi, Dalila B.-
dc.contributor.authorHipp, Jennifer-
dc.contributor.authorHong, Huixiao-
dc.contributor.authorHorvath, Kyle-
dc.contributor.authorHu, Jianhong-
dc.contributor.authorSchulze, Egbert-
dc.contributor.authorHung, Li Yuan-
dc.contributor.authorJarosz, Mirna-
dc.contributor.authorKerkhof, Jennifer-
dc.contributor.authorKipp, Benjamin-
dc.contributor.authorKreil, David Philip-
dc.contributor.authorMeng, Qingchang-
dc.contributor.authorŁabaj, Paweł-
dc.contributor.authorLapunzina, Pablo-
dc.contributor.authorLi, Peng-
dc.contributor.authorLi, Quan Zhen-
dc.contributor.authorLi, Weihua-
dc.contributor.authorSebra, Robert-
dc.contributor.authorLi, Zhiguang-
dc.contributor.authorLiang, Yu-
dc.contributor.authorLiu, Shaoqing-
dc.contributor.authorLiu, Zhichao-
dc.contributor.authorMieczkowski, Piotr A.-
dc.contributor.authorMa, Charles-
dc.contributor.authorShaknovich, Rita-
dc.contributor.authorMorrison, Tom-
dc.contributor.authorMuzny, Donna-
dc.contributor.authorNing, Baitang-
dc.contributor.authorParsons, Barbara L.-
dc.contributor.authorXiao, Wenzhong-
dc.contributor.authorPaweletz, Cloud P.-
dc.contributor.authorPirooznia, Mehdi-
dc.contributor.authorQu, Wubin-
dc.contributor.authorRaymond, Amelia-
dc.contributor.authorRindler, Paul-
dc.contributor.authorRingler, Rebecca-
dc.contributor.authorShi, Qiang-
dc.contributor.authorSadikovic, Bekim-
dc.contributor.authorShi, Tieliu-
dc.contributor.authorSilla-Castro, Juan Carlos-
dc.contributor.authorXu, Shibei-
dc.contributor.authorSmith, Melissa-
dc.contributor.authorLópez, Mario Solís-
dc.contributor.authorSong, Ping-
dc.contributor.authorLader, Eric-
dc.contributor.authorStetson, Daniel-
dc.contributor.authorStrahl, Maya-
dc.contributor.authorStuart, Alan-
dc.contributor.authorSupplee, Julianna-
dc.contributor.authorSzankasi, Philippe-
dc.contributor.authorTan, Haowen-
dc.contributor.authorYang, Mary-
dc.contributor.authorTang, Lin ya-
dc.contributor.authorTao, Yonghui-
dc.contributor.authorThakkar, Shraddha-
dc.contributor.authorThierry-Mieg, Danielle-
dc.contributor.authorRichmond, Todd A.-
dc.contributor.authorThierry-Mieg, Jean-
dc.contributor.authorThodima, Venkat J.-
dc.contributor.authorThomas, David-
dc.contributor.authorTichý, Boris-
dc.contributor.authorTom, Nikola-
dc.contributor.authorYing, Jianming-
dc.contributor.authorGarcia, Elena Vallespin-
dc.contributor.authorVerma, Suman-
dc.contributor.authorWalker, Kimbley-
dc.contributor.authorWang, Charles-
dc.contributor.authorWang, Junwen-
dc.contributor.authorMittal, Vinay K.-
dc.contributor.authorWang, Yexun-
dc.contributor.authorWen, Zhining-
dc.contributor.authorWirta, Valtteri-
dc.contributor.authorWu, Leihong-
dc.contributor.authorYip, Shun H.-
dc.contributor.authorXiao, Chunlin-
dc.contributor.authorLiu, Liang Chun-
dc.contributor.authorZhang, Guangliang-
dc.contributor.authorZhang, Sa-
dc.contributor.authorZhao, Meiru-
dc.contributor.authorZheng, Yuanting-
dc.contributor.authorCraig, Daniel J.-
dc.contributor.authorZhou, Xiaoyan-
dc.contributor.authorMason, Christopher E.-
dc.contributor.authorMercer, Timothy-
dc.contributor.authorTong, Weida-
dc.contributor.authorShi, Leming-
dc.contributor.authorJones, Wendell-
dc.contributor.authorJohann, Donald J.-
dc.contributor.authorXu, Joshua-
dc.contributor.authorWilley, James C.-
dc.contributor.authorBushel, Pierre R.-
dc.contributor.authorCrawford, Erin-
dc.contributor.authorYu, Ying-
dc.contributor.authorXu, Chang-
dc.contributor.authorChen, Guangchun-
dc.contributor.authorBurgess, Daniel-
dc.contributor.authorCawley, Simon-
dc.contributor.authorGiorda, Kristina-
dc.contributor.authorHaseley, Nathan-
dc.contributor.authorQiu, Fujun-
dc.contributor.authorWilkins, Katherine-
dc.contributor.authorArib, Hanane-
dc.contributor.authordel Pozo, Angela-
dc.contributor.authorAttwooll, Claire-
dc.contributor.authorBabson, Kevin-
dc.contributor.authorBao, Longlong-
dc.contributor.authorBao, Wenjun-
dc.contributor.authorLucas, Anne Bergstrom-
dc.date.accessioned2023-02-03T07:03:39Z-
dc.date.available2023-02-03T07:03:39Z-
dc.date.issued2021-
dc.identifier.citationGenome Biology, 2021, v. 22, n. 1, article no. 109-
dc.identifier.issn1474-7596-
dc.identifier.urihttp://hdl.handle.net/10722/324511-
dc.description.abstractBackground: Targeted sequencing using oncopanels requires comprehensive assessments of accuracy and detection sensitivity to ensure analytical validity. By employing reference materials characterized by the U.S. Food and Drug Administration-led SEquence Quality Control project phase2 (SEQC2) effort, we perform a cross-platform multi-lab evaluation of eight Pan-Cancer panels to assess best practices for oncopanel sequencing. Results: All panels demonstrate high sensitivity across targeted high-confidence coding regions and variant types for the variants previously verified to have variant allele frequency (VAF) in the 5–20% range. Sensitivity is reduced by utilizing VAF thresholds due to inherent variability in VAF measurements. Enforcing a VAF threshold for reporting has a positive impact on reducing false positive calls. Importantly, the false positive rate is found to be significantly higher outside the high-confidence coding regions, resulting in lower reproducibility. Thus, region restriction and VAF thresholds lead to low relative technical variability in estimating promising biomarkers and tumor mutational burden. Conclusion: This comprehensive study provides actionable guidelines for oncopanel sequencing and clear evidence that supports a simplified approach to assess the analytical performance of oncopanels. It will facilitate the rapid implementation, validation, and quality control of oncopanels in clinical use.-
dc.languageeng-
dc.relation.ispartofGenome Biology-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectAnalytical performance-
dc.subjectMolecular diagnostics-
dc.subjectOncopanel sequencing-
dc.subjectPrecision medicine-
dc.subjectReproducibility-
dc.subjectTarget enrichment-
dc.titleCross-oncopanel study reveals high sensitivity and accuracy with overall analytical performance depending on genomic regions-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1186/s13059-021-02315-0-
dc.identifier.pmid33863344-
dc.identifier.pmcidPMC8051090-
dc.identifier.scopuseid_2-s2.0-85104386329-
dc.identifier.volume22-
dc.identifier.issue1-
dc.identifier.spagearticle no. 109-
dc.identifier.epagearticle no. 109-
dc.identifier.eissn1474-760X-
dc.identifier.isiWOS:000641654300001-

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