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 language | English |
|---|---|
| Article number | 83 |
| Pages (from-to) | 83 |
| Journal | Biomarker research |
| Volume | 10 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 1 Dec 2022 |
Bibliographical note
© 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),\u00A0Nerea G\u00F3mez de San Jos\u00E9 (University of Ulm)\u00A0and Jose Gavald\u00E1-Garc\u00ED\u00ADa (Vrije Universiteit Brussel). We are grateful to Dr. Anita Bandrowski for providing us with additional information about the Antibody Registry. KW, EW, EV, HZ, CT and SA received funding from the European Union\u2019s Horizon 2020 research and innovation programme under the Marie Sk\u0142odowska-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\u2019s Association (#ADSF-21-831376-C, #ADSF-21-831381-C and #ADSF-21-831377-C), the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen f\u00F6r Gamla Tj\u00E4narinnor, Hj\u00E4rnfonden, 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. 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.
| Funders | Funder number |
|---|---|
| Nerea Gómez de San José | |
| Familjen Erling-Perssons Stiftelse | |
| AC-Immune | |
| Edwin Bouw Fonds and Gieskes-Strijbisfonds | |
| Universität Ulm | |
| EU Joint Programme – Neurodegenerative Disease Research | |
| UK Dementia Research Institute | |
| Eli Lilly and Company | |
| Health~Holland | |
| Roche | |
| ZonMw | |
| Olav Thon Stiftelsen | |
| Yanaika Hok-A-Hin | |
| European Research Council | |
| AD Strategic Fund | |
| Alzheimer's Association | -21-831376-C, -21-831377-C, 73305095007 |
| Vetenskapsrådet | 2018-02532 |
| Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden | 2019-0228 |
| Alzheimer's Drug Discovery Foundation | 201809-2016862 |
| Horizon 2020 Framework Programme | 681712 |
| Nederlandse Organisatie voor Wetenschappelijk Onderzoek | 680-91-112 |
| H2020 Marie Skłodowska-Curie Actions | 860197 |
| Topsector Life Sciences & Health | 20106 |
| Swedish State Support for Clinical Research | -720931 |