Bioinformatics tools and data resources for assay development of fluid protein biomarkers

  • Katharina Waury
  • , Eline A.J. Willemse
  • , Eugeen Vanmechelen
  • , Henrik Zetterberg
  • , Charlotte E. Teunissen
  • , Sanne Abeln*
  • *Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

Fluid protein biomarkers are important tools in clinical research and health care to support diagnosis and to monitor patients. Especially within the field of dementia, novel biomarkers could address the current challenges of providing an early diagnosis and of selecting trial participants. While the great potential of fluid biomarkers is recognized, their implementation in routine clinical use has been slow. One major obstacle is the often unsuccessful translation of biomarker candidates from explorative high-throughput techniques to sensitive antibody-based immunoassays. In this review, we propose the incorporation of bioinformatics into the workflow of novel immunoassay development to overcome this bottleneck and thus facilitate the development of novel biomarkers towards clinical laboratory practice. Due to the rapid progress within the field of bioinformatics many freely available and easy-to-use tools and data resources exist which can aid the researcher at various stages. Current prediction methods and databases can support the selection of suitable biomarker candidates, as well as the choice of appropriate commercial affinity reagents. Additionally, we examine methods that can determine or predict the epitope - an antibody’s binding region on its antigen - and can help to make an informed choice on the immunogenic peptide used for novel antibody production. Selected use cases for biomarker candidates help illustrate the application and interpretation of the introduced tools.

Original languageEnglish
Article number83
JournalBiomarker Research
Volume10
Issue number1
DOIs
Publication statusPublished - Dec 2022
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2022, The Author(s).

Funding

We would like to thank the researchers who gave us insight into their work, their thoughts and suggestions regarding the improvement of immunoassay development: Dr. Marta del Campo (San Pablo CEU University), Dr. Marleen Koel-Simmelink (VUmc), Yanaika Hok-A-Hin (VUmc), Lynn Boonkamp (VUmc), Nerea Gómez de San José (University of Ulm) and Jose Gavaldá-Garcí­a (Vrije Universiteit Brussel). We are grateful to Dr. Anita Bandrowski for providing us with additional information about the Antibody Registry. EV is a co-founder of ADx NeuroSciences. HZ has served at scientific advisory boards and/or as a consultant for Abbvie, Alector, Eisai, Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics, Nervgen, AZTherapies, CogRx, and Red Abbey Labs, has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure and Biogen, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (all outside submitted work). CT has a collaboration contract with ADx Neurosciences, Quanterix and Eli Lilly, performed contract research or received grants from AC-Immune, Axon Neurosciences, Biogen, Brainstorm Therapeutics, Celgene, EIP Pharma, Eisai, PeopleBio, Roche, Toyama, Vivoryon, and has a speaker contract with Roche.The MIRIADE project includes the following commercial beneficiaries and partners: ADxNeuroscience, ENPICOM, LGC Limited, PeopleBio, Inc., Olink, Quanterix, and Roche. KW, EW, EV, HZ, CT and SA received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860197, the MIRIADE project. HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG-720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), the AD Strategic Fund and the Alzheimer’s Association (#ADSF-21-831376-C, #ADSF-21-831381-C and #ADSF-21-831377-C), the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2019-0228), and the UK Dementia Research Institute at UCL. Research of CT is supported by JPND (bPRIDE), Health Holland, the Dutch Research Council (ZonMW), Alzheimer Drug Discovery Foundation, The Selfridges Group Foundation, Alzheimer Netherlands, and Alzheimer Association. CT is recipient of ABOARD, which is a public-private partnership receiving funding from ZonMW (#73305095007) and Health-Holland, Topsector Life Sciences & Health (PPP-allowance; #LSHM20106). More than 30 partners participate in ABOARD. ABOARD also receives funding from Edwin Bouw Fonds and Gieskes-Strijbisfonds. SA receives funding from the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO) under project number number 680-91-112.

FundersFunder number
AC Immune SA
AD Strategic Fund
Edwin Bouw Fonds and Gieskes-Strijbisfonds
Nerea Gómez de San José
Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden2019-0228
Swedish State Support for Clinical Research-720931
Topsector Life Sciences & Health20106
Yanaika Hok-A-Hin
Alzheimer's Association-21-831376-C, -21-831377-C, 73305095007
Alzheimer's Drug Discovery Foundation201809-2016862
Eli Lilly and Company
Roche
Familjen Erling-Perssons Stiftelse
Horizon 2020 Framework Programme
H2020 Marie Skłodowska-Curie Actions860197
EU Joint Programme – Neurodegenerative Disease Research
Utrecht University
European Research Council681712
ZonMw
Nederlandse Organisatie voor Wetenschappelijk Onderzoek680-91-112
Vetenskapsrådet2018-02532
Ulm University
UK Dementia Research Institute
Olav Thon Stiftelsen

    Keywords

    • Antibody
    • Bioinformatics
    • Biomarker
    • Dementia
    • Immunoassay

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