A reproducible approach for the use of aptamer libraries for the identification of Aptamarkers for brain amyloid deposition based on plasma analysis

PLoS One. 2024 Aug 27;19(8):e0307678. doi: 10.1371/journal.pone.0307678. eCollection 2024.

Abstract

An approach for the agnostic identification and validation of aptamers for the prediction of a medical state from plasma analysis is presented in application to a key risk factor for Alzheimer's disease. brain amyloid deposition. This method involved the use of a newly designed aptamer library with sixteen random nucleotides interspersed with fixed sequences called a Neomer library. The Neomer library approach enables the direct application of the same starting library on multiple plasma samples, without the requirement for pre-enrichment associated with the traditional approach. Eight aptamers were identified as a result of the selection process and screened across 390 plasma samples by qPCR assay. Results were analysed using multiple machine learning algorithms from the Scikit-learn package along with clinical variables including cognitive status, age and sex to create predictive models. An Extra Trees Classifier model provided the highest predictive power. The Neomer approach resulted in a sensitivity of 0.88. specificity of 0.76. and AUC of 0.79. The only clinical variables that were included in the model were age and sex. We conclude that the Neomer approach represents a clear improvement for the agnostic identification of aptamers (Aptamarkers) that bind to unknown biomarkers of a medical state.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease* / blood
  • Alzheimer Disease* / diagnosis
  • Amyloid / metabolism
  • Aptamers, Nucleotide* / chemistry
  • Biomarkers / blood
  • Brain* / metabolism
  • Female
  • Humans
  • Machine Learning
  • Male
  • Middle Aged
  • Reproducibility of Results
  • SELEX Aptamer Technique* / methods

Substances

  • Aptamers, Nucleotide
  • Biomarkers
  • Amyloid

Grants and funding

The study was funded by NeoVentures Biotechnology Europe SAS and the Alzheimer’s Drug Discovery Foundation (project entitled "Blood diagnostic test for AD: aptamer deep biomarker fingerprinting", reference # GDAPB-201808-2016228) through a grant in 2020. During the course of this study, NeoVentures Biotechnology Europe was financially supported by NeoVentures Biotechnology Inc. The funders had a role in the study design, data analysis, decision to publish, and preparation of this manuscript. S. Lecocq and C. Meehan are employees of NeoVentures Biotechnology Europe. G. Penner is an employee of NeoVentures Biotechnology Inc.