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

Author

Gong, B, Li, D, Kusko, R, Novoradovskaya, N, Zhang, Y, Wang, S, Pabón-Peña, C, Zhang, Z, Lai, K, Cai, W, LoCoco, JS, Lader, E, Richmond, TA, Mittal, VK, Liu, LC, Johann, DJ, Willey, JC, Bushel, PR, Yu, Y, Xu, C, Chen, G, Burgess, D, Cawley, S, Giorda, K, Haseley, N, Qiu, F, Wilkins, K, Arib, H, Attwooll, C, Babson, K, Bao, L, Bao, W, Lucas, AB, Best, H, Bhandari, A, Bisgin, H, Blackburn, J, Blomquist, TM, Boardman, L, Burgher, B, Butler, DJ, Chang, CJ, Chaubey, A, Chen, T, Chierici, M, Chin, CR, Close, D, Conroy, J, Coleman, JC, Craig, DJ, Crawford, E, del Pozo, A, Deveson, IW, Duncan, D, Eterovic, AK, Fan, X, Foox, J, Furlanello, C, Ghosal, A, Glenn, S, Guan, M, Haag, C, Hang, X, Happe, S, Hennigan, B, Hipp, J, Hong, H, Horvath, K, Hu, J, Hung, LY, Jarosz, M, Kerkhof, J, Kipp, B, Kreil, DP, Łabaj, P, Lapunzina, P, Li, P, Li, QZ, Li, W, Li, Z, Liang, Y, Liu, S, Liu, Z, Ma, C, Marella, N, Martín-Arenas, R, Megherbi, DB, Meng, Q, Mieczkowski, PA, Morrison, T, Muzny, D, Ning, B, Parsons, BL, Paweletz, CP, Pirooznia, M, Qu, W, Raymond, A, Rindler, P, Ringler, R, Sadikovic, B, Gong, B, Li, D, Kusko, R, Novoradovskaya, N, Zhang, Y, Wang, S, Pabón-Peña, C, Zhang, Z, Lai, K, Cai, W, LoCoco, JS, Lader, E, Richmond, TA, Mittal, VK, Liu, LC, Johann, DJ, Willey, JC, Bushel, PR, Yu, Y, Xu, C, Chen, G, Burgess, D, Cawley, S, Giorda, K, Haseley, N, Qiu, F, Wilkins, K, Arib, H, Attwooll, C, Babson, K, Bao, L, Bao, W, Lucas, AB, Best, H, Bhandari, A, Bisgin, H, Blackburn, J, Blomquist, TM, Boardman, L, Burgher, B, Butler, DJ, Chang, CJ, Chaubey, A, Chen, T, Chierici, M, Chin, CR, Close, D, Conroy, J, Coleman, JC, Craig, DJ, Crawford, E, del Pozo, A, Deveson, IW, Duncan, D, Eterovic, AK, Fan, X, Foox, J, Furlanello, C, Ghosal, A, Glenn, S, Guan, M, Haag, C, Hang, X, Happe, S, Hennigan, B, Hipp, J, Hong, H, Horvath, K, Hu, J, Hung, LY, Jarosz, M, Kerkhof, J, Kipp, B, Kreil, DP, Łabaj, P, Lapunzina, P, Li, P, Li, QZ, Li, W, Li, Z, Liang, Y, Liu, S, Liu, Z, Ma, C, Marella, N, Martín-Arenas, R, Megherbi, DB, Meng, Q, Mieczkowski, PA, Morrison, T, Muzny, D, Ning, B, Parsons, BL, Paweletz, CP, Pirooznia, M, Qu, W, Raymond, A, Rindler, P, Ringler, R, and Sadikovic, B

Abstract

Background: 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.

Published
2021

19. Index

Author

Beehler, Bruce M., Evans, Middleton, Ringler, Robert F., and Robbins, Chandler S.

Published
2019

20. 29 Best Birding Localities

Author

Beehler, Bruce M., Evans, Middleton, Ringler, Robert F., and Robbins, Chandler S.

Published
2019

22. Addendum

Author

Beehler, Bruce M., Evans, Middleton, Ringler, Robert F., and Robbins, Chandler S.

Published
2019

23. Photography Notes

Author

Beehler, Bruce M., Evans, Middleton, Ringler, Robert F., and Robbins, Chandler S.

Published
2019

24. Part IV Bird-Finding Guide

Author

Beehler, Bruce M., Evans, Middleton, Ringler, Robert F., and Robbins, Chandler S.

Published
2019

26. Contributors

Author

Beehler, Bruce M., Evans, Middleton, Ringler, Robert F., and Robbins, Chandler S.

Published
2019

31. 22 Necessary Birding Gear

Author

Beehler, Bruce M., Evans, Middleton, Ringler, Robert F., and Robbins, Chandler S.

Published
2019

35. Part III Birding Tools

Author

Beehler, Bruce M., Evans, Middleton, Ringler, Robert F., and Robbins, Chandler S.

Published
2019

38. 14 Birds of Prey

Author

Beehler, Bruce M., Evans, Middleton, Ringler, Robert F., and Robbins, Chandler S.

Published
2019

39. 16 Aerial Feeders

Author

Beehler, Bruce M., Evans, Middleton, Ringler, Robert F., and Robbins, Chandler S.

Published
2019

40. The Landbirds

Author

Beehler, Bruce M., Evans, Middleton, Ringler, Robert F., and Robbins, Chandler S.

Published
2019

42. 13 Birds of the Open Ocean

Author

Beehler, Bruce M., Evans, Middleton, Ringler, Robert F., and Robbins, Chandler S.

Published
2019

43. 12 Shorebirds

Author

Beehler, Bruce M., Evans, Middleton, Ringler, Robert F., and Robbins, Chandler S.

Published
2019

44. 11 Coastal Waterbirds

Author

Beehler, Bruce M., Evans, Middleton, Ringler, Robert F., and Robbins, Chandler S.

Published
2019

45. 10 Marsh and Wading Birds

Author

Beehler, Bruce M., Evans, Middleton, Ringler, Robert F., and Robbins, Chandler S.

Published
2019

46. The Waterbirds

Author

Beehler, Bruce M., Evans, Middleton, Ringler, Robert F., and Robbins, Chandler S.

Published
2019

47. 9 The Waterfowl

Author

Beehler, Bruce M., Evans, Middleton, Ringler, Robert F., and Robbins, Chandler S.

Published
2019

49. Part II Bird Group Accounts

Author

Beehler, Bruce M., Evans, Middleton, Ringler, Robert F., and Robbins, Chandler S.

Published
2019

50. 5 The Gift of Wild Places

Author

Beehler, Bruce M., Evans, Middleton, Ringler, Robert F., and Robbins, Chandler S.

Published
2019

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