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

被引：29

作者：

Gong, Binsheng ^{[1
]}

Li, Dan ^{[1
]}

Kusko, Rebecca ^{[2
]}

Novoradovskaya, Natalia ^{[3
]}

Zhang, Yifan ^{[1
,4
]}

Wang, Shangzi ^{[5
,6
]}

Pabon-Pena, Carlos ^{[7
]}

Zhang, Zhihong ^{[8
]}

Lai, Kevin ^{[9
]}

Cai, Wanshi ^{[10
]}

LoCoco, Jennifer S. ^{[11
]}

Lader, Eric ^{[12
]}

Richmond, Todd A. ^{[13
]}

Mittal, Vinay K. ^{[14
]}

Liu, Liang-Chun ^{[15
]}

Johann, Donald J., Jr. ^{[16
]}

Willey, James C. ^{[17
,18
]}

Bushel, Pierre R. ^{[19
]}

Yu, Ying ^{[5
,6
]}

Xu, Chang ^{[12
]}

Chen, Guangchun ^{[20
]}

Burgess, Daniel ^{[21
]}

Cawley, Simon ^{[22
]}

Giorda, Kristina ^{[23
]}

Haseley, Nathan ^{[11
]}

Qiu, Fujun ^{[8
]}

Wilkins, Katherine ^{[7
]}

Arib, Hanane ^{[24
,25
]}

Attwooll, Claire ^{[11
]}

Babson, Kevin ^{[26
]}

Bao, Longlong ^{[27
,28
,29
]}

Bao, Wenjun ^{[30
]}

Lucas, Anne Bergstrom ^{[7
]}

Best, Hunter ^{[31
,32
]}

Bhandari, Ambica ^{[33
]}

Bisgin, Halil ^{[34
]}

Blackburn, James ^{[35
,36
]}

Blomquist, Thomas M. ^{[37
,38
]}

Boardman, Lisa ^{[39
]}

Burgher, Blake ^{[40
]}

Butler, Daniel J. ^{[41
]}

Chang, Chia-Jung ^{[42
]}

Chaubey, Alka ^{[26
]}

Chen, Tao ^{[43
]}

Chierici, Marco ^{[44
]}

Chin, Christopher R. ^{[41
]}

Close, Devin ^{[32
]}

Conroy, Jeffrey ^{[40
]}

Coleman, Jessica Cooley ^{[26
]}

Craig, Daniel J. ^{[45
]}

机构：

[1] US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA

[2] Immuneering Corp, One Broadway,14th Floor, Cambridge, MA 02142 USA

[3] Agilent Technol, 11011 N Torrey Pines Rd, La Jolla, CA 92037 USA

[4] Univ Arkansas, Dept Informat Sci, 2801 S Univ Ave, Little Rock, AR 72204 USA

[5] Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Canc Inst, Shanghai 200438, Peoples R China

[6] Fudan Univ, Shanghai Canc Hosp, State Key Lab Genet Engn, Canc Inst, Shanghai 200438, Peoples R China

[7] Agilent Technol, 5301 Stevens Creek Blvd, Santa Clara, CA 95051 USA

[8] Burning Rock Biotech, Res & Dev, Shanghai 201114, Peoples R China

[9] Integrated DNA Technol Inc, Bioinformat, 1710 Commercial Pk, Coralville, IA 52241 USA

[10] iGeneTech, 8 Shengmingyuan Rd,Zhongguancun Life Sci Pk, Beijing 100080, Peoples R China

[11] Illumina Inc, 5200 Illumina Way, San Diego, CA 92122 USA

[12] QIAGEN Sci Inc, Res & Dev, Frederick, MD 21703 USA

[13] Roche Sequencing Solut Inc, Mkt & Applicat Dev Bioinformat, 4300 Hacienda Dr, Pleasanton, CA 94588 USA

[14] Thermo Fisher Sci, 110 Miller Ave, Ann Arbor, MI 48104 USA

[15] Thermo Fisher Sci, Clin Diagnost Div, 46500 Kato Rd, Fremont, CA 94538 USA

[16] Univ Arkansas Med Sci, Winthrop P Rockefeller Canc Inst, 4301 Markham St, Little Rock, AR 72205 USA

[17] Univ Toledo, Dept Med Pathol, Coll Med & Life Sci, Hlth Sci Campus,3000 Arlington Ave, Toledo, OH 43614 USA

[18] Univ Toledo, Dept Canc Biol, Coll Med & Life Sci, Hlth Sci Campus,3000 Arlington Ave, Toledo, OH 43614 USA

[19] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA

[20] Univ Texas Southwestern Med Ctr Dallas, Dept Immunol Genom & Microarray Core Facil, 5323 Harry Hine Blvd, Dallas, TX 75390 USA

[21] Roche Sequencing Solut Inc, Res & Dev, 500 South Rosa Rd, Madison, WI 53719 USA

[22] Thermo Fisher Sci, Clin Sequencing Div, 180 Oyster Point Blvd, San Francisco, CA 94080 USA

[23] Integrated DNA Technol Inc, Mkt, 1710 Commercial Pk, Coralville, IA 52241 USA

[24] Icahn Sch Med Mt Sinai, Icahn Inst, 1425 Madison Ave, New York, NY 10029 USA

[25] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, 1425 Madison Ave, New York, NY 10029 USA

[26] Greenwood Genet Ctr, 106 Gregor Mendel Circle, Greenwood, SC 29646 USA

[27] Fudan Univ, Shanghai Canc Ctr, Dept Pathol, Shanghai 200032, Peoples R China

[28] Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai 200032, Peoples R China

[29] Fudan Univ, Inst Pathol, Shanghai 200032, Peoples R China

[30] SAS Inst Inc, JMP Life Sci, Cary, NC 27519 USA

[31] Univ Utah, Dept Pathol, Sch Med, Salt Lake City, UT 84108 USA

[32] Inst Clin & Expt Pathol, R&D Genom MPS, ARUP Labs, 500 Chipeta Way, Salt Lake City, UT 84108 USA

[33] ResearchDx Inc, 5 Mason, Irvine, CA 92618 USA

[34] Univ Michigan, Dept Comp Sci Engn & Phys, Flint, MI 48502 USA

[35] Garvan Inst Med Res, Sydney, NSW, Australia

[36] Univ New South Wales, St Vincents Clin Sch, Sydney, NSW 2010, Australia

[37] Univ Toledo, Coll Med & Life Sci, Dept Pathol, Toledo, OH 43614 USA

[38] Lucas Cty Coroners Off, 2595 Arlington Ave, Toledo, OH 43614 USA

[39] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN 55905 USA

[40] OmniSeq Inc, 700 Ellicott St, Buffalo, NY 14203 USA

[41] Cornell Univ, Dept Physiol & Biophys, Weill Cornell Med, New York, NY 10065 USA

[42] Stanford Univ, Stanford Genome Technol Ctr, Palo Alto, CA 94304 USA

[43] US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA

[44] Fdn Bruno Kessler, I-38123 Trento, Italy

[45] Univ Toledo, Coll Med & Life Sci, Dept Med, Toledo, OH 43614 USA

[46] Hosp Univ La Paz, Inst Med & Mol Genet INGEMM, Inst Salud Carlos III, CIBERER, Madrid 28046, Spain

[47] European Infrastruct Translat Med, EATRIS ERIC, Boelelaan 1118, NL-1081 HZ Amsterdam, Netherlands

[48] Garvan Inst Med Res, Kinghorn Ctr Clin Genom, Sydney, NSW, Australia

[49] Univ New South Wales, Fac Med, St Vincents Clin Sch, Sydney, NSW, Australia

[50] Canc Genet Inc, 201 Route 17 N,Meadows Off Bldg, Rutherford, NJ 07070 USA

来源：

GENOME BIOLOGY | 2021年 / 22卷 / 01期

基金：

美国国家卫生研究院; 英国医学研究理事会; 中国国家自然科学基金;

关键词：

Oncopanel sequencing; Target enrichment; Molecular diagnostics; Reproducibility; Analytical performance; Precision medicine; TUMOR MUTATIONAL BURDEN; LUNG-CANCER PATIENTS; QUALITY-CONTROL; IMPACT; VALIDATION; BIOMARKER; TARGETS; ASSAY;

D O I：

10.1186/s13059-021-02315-0

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

BackgroundTargeted 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.ResultsAll 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.ConclusionThis 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.

引用

页数：23

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