How Controls Improve Diagnostic Assay Performance: Hitchhiker's Guide to Diagnostic Assay Controls

To have confidence that results from diagnostic assays for plant pathogens are accurate and to identify potential problems with false negatives and false positives, it is essential that the appropriate control reactions are included in the assay design. This review discusses control reactions that,...

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Main Authors: Frank N. Martin, Ozgur Batuman, Douglas G. Luster, Timothy D. Miles, Yazmín Rivera, Poonam Sharma, David Geiser, Kitty Cardwell
Format: Article
Language:English
Published: The American Phytopathological Society 2025-06-01
Series:PhytoFrontiers
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Online Access:https://apsjournals.apsnet.org/doi/10.1094/PHYTOFR-10-24-0118-FI
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author Frank N. Martin
Ozgur Batuman
Douglas G. Luster
Timothy D. Miles
Yazmín Rivera
Poonam Sharma
David Geiser
Kitty Cardwell
author_facet Frank N. Martin
Ozgur Batuman
Douglas G. Luster
Timothy D. Miles
Yazmín Rivera
Poonam Sharma
David Geiser
Kitty Cardwell
author_sort Frank N. Martin
collection DOAJ
description To have confidence that results from diagnostic assays for plant pathogens are accurate and to identify potential problems with false negatives and false positives, it is essential that the appropriate control reactions are included in the assay design. This review discusses control reactions that, depending on the technology used, should be either run in parallel or multiplexed with the diagnostic assay to ensure accuracy. The discussion includes immunoassays such as enzyme-linked immunosorbent assay and lateral flow devices, as well as molecular diagnostic techniques including PCR, isothermal technologies (recombinant polymerase amplification and loop-mediated isothermal amplification), and high-throughput sequencing. Additional details are provided for RNA virus assays that account for the need for a control reaction during the generation of complementary DNA. Although concepts of control reaction design and the reasons for their inclusion are discussed, the reader is directed to the Diagnostic Assay Validation Network website hosted on the American Phytopathological Society website for specific examples of control reactions reported in the literature that may be useful to consider when designing new diagnostic assays. [Figure: see text] Copyright © 2025 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.
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spelling doaj-art-dfbf96b269bc4889afe366565aa1d22a2025-08-20T03:29:18ZengThe American Phytopathological SocietyPhytoFrontiers2690-54422025-06-015212713710.1094/PHYTOFR-10-24-0118-FIHow Controls Improve Diagnostic Assay Performance: Hitchhiker's Guide to Diagnostic Assay ControlsFrank N. Martin0Ozgur Batuman1Douglas G. Luster2Timothy D. Miles3Yazmín Rivera4Poonam Sharma5David Geiser6Kitty Cardwell7USDA-ARS, 1636 East Alisal St., Salinas, CA 93905, U.S.A.University of Florida, Southwest Florida Research and Education Center, 2685 SR 29 North Immokalee, FL 34142, U.S.A.USDA-ARS-NEA, Foreign Disease-Weed Science Research Unit, 1301 Ditto Avenue, Fort Detrick, MD 21702, U.S.A.Small Fruit & Hop Pathology Program, Department of Plant, Soil and Microbial Sciences, Michigan State University, East Lansing, MI 48824, U.S.A.Plant Pathogen Confirmatory Diagnostics Laboratory (Beltsville Laboratory), USDA APHIS PPQ, Science and Technology, Bldg 580, BARC-East, 9901 Powder Mill Rd., Laurel, MD 20708, U.S.A.Institute of Biosecurity and Microbial Forensics, Department of Entomology and Plant Pathology, 127 NRC, Oklahoma State University, Stillwater, OK 74078, U.S.A.Department of Plant Pathology and Environmental Microbiology, 121 Buckhout Lab, Penn State University, University Park, PA 16802, U.S.A.Institute of Biosecurity and Microbial Forensics, Department of Entomology and Plant Pathology, 127 NRC, Oklahoma State University, Stillwater, OK 74078, U.S.A.To have confidence that results from diagnostic assays for plant pathogens are accurate and to identify potential problems with false negatives and false positives, it is essential that the appropriate control reactions are included in the assay design. This review discusses control reactions that, depending on the technology used, should be either run in parallel or multiplexed with the diagnostic assay to ensure accuracy. The discussion includes immunoassays such as enzyme-linked immunosorbent assay and lateral flow devices, as well as molecular diagnostic techniques including PCR, isothermal technologies (recombinant polymerase amplification and loop-mediated isothermal amplification), and high-throughput sequencing. Additional details are provided for RNA virus assays that account for the need for a control reaction during the generation of complementary DNA. Although concepts of control reaction design and the reasons for their inclusion are discussed, the reader is directed to the Diagnostic Assay Validation Network website hosted on the American Phytopathological Society website for specific examples of control reactions reported in the literature that may be useful to consider when designing new diagnostic assays. [Figure: see text] Copyright © 2025 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.https://apsjournals.apsnet.org/doi/10.1094/PHYTOFR-10-24-0118-FIdiagnostic assayELISAisothermal amplificationLAMPlateral flowNGS/HTS
spellingShingle Frank N. Martin
Ozgur Batuman
Douglas G. Luster
Timothy D. Miles
Yazmín Rivera
Poonam Sharma
David Geiser
Kitty Cardwell
How Controls Improve Diagnostic Assay Performance: Hitchhiker's Guide to Diagnostic Assay Controls
PhytoFrontiers
diagnostic assay
ELISA
isothermal amplification
LAMP
lateral flow
NGS/HTS
title How Controls Improve Diagnostic Assay Performance: Hitchhiker's Guide to Diagnostic Assay Controls
title_full How Controls Improve Diagnostic Assay Performance: Hitchhiker's Guide to Diagnostic Assay Controls
title_fullStr How Controls Improve Diagnostic Assay Performance: Hitchhiker's Guide to Diagnostic Assay Controls
title_full_unstemmed How Controls Improve Diagnostic Assay Performance: Hitchhiker's Guide to Diagnostic Assay Controls
title_short How Controls Improve Diagnostic Assay Performance: Hitchhiker's Guide to Diagnostic Assay Controls
title_sort how controls improve diagnostic assay performance hitchhiker s guide to diagnostic assay controls
topic diagnostic assay
ELISA
isothermal amplification
LAMP
lateral flow
NGS/HTS
url https://apsjournals.apsnet.org/doi/10.1094/PHYTOFR-10-24-0118-FI
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