(588br) ML Prediction of High-Affinity Aptamers for Novel Biological Vectors for Biosensor Applications

Rapid detection and identification of biological pathogens are crucial for fighting contagious pathogens and deterring biological threats. Probes that have both high affinity and specificity to a pathogen are critical for developing and employing biosensors. Single-stranded oligonucleotides have been shown to demonstrate both high affinity and specificity in specific cases.^1,2 The chemical synthesis process for oligonucleotides also alleviates the batch issues associated with peptide and antibody production.³ While high affinity and specific aptamers can be identified through the process known as Systematic Evolution of Ligands by EXponential (SELEX) enrichment, SELEX and its modified versions are time-consuming, costly, and have a low success rate.⁴ To consistently and rapidly identify high affinity and specific aptamers, we proposed a machine learning method to design sequences for specific pathogenic targets. We demonstrate that classical machine learning methods can predict oligonucleotide sequences binding to target proteins. Currently, our focus is on generating a more robust dataset of high affinity oligonucleotides and testing their specificity; the expanded dataset will facilitate development of higher performing machine learning models, such as a graphical neural network. The results of this study will enable rapid design of high affinity oligonucleotides solely based on the target’s amino acid sequence.

Corresponding Author: LTC Stephen G. Hummel, PhD, Dept of Chemistry and Life Science, United States Military Academy, West Point, New York 10996. Email: stephen.hummel@westpoint.edu

REFERENCES

(1) Zichel, R.; Chearwae, W.; Pandey, G. S.; Golding, B.; Sauna, Z. E. Aptamers as a Sensitive Tool to Detect Subtle Modifications in Therapeutic Proteins. PloS One 2012, 7 (2), e31948. https://doi.org/10.1371/journal.pone.0031948.

(2) Gomes de Castro, M. A.; Höbartner, C.; Opazo, F. Aptamers Provide Superior Stainings of Cellular Receptors Studied under Super-Resolution Microscopy. PloS One 2017, 12 (2), e0173050. https://doi.org/10.1371/journal.pone.0173050.

(3) Dong, H.; Han, L.; Wu, Z.-S.; Zhang, T.; Xie, J.; Ma, J.; Wang, J.; Li, T.; Gao, Y.; Shao, J.; Sinko, P. J.; Jia, L. Biostable Aptamer Rings Conjugated for Targeting Two Biomarkers on Circulating Tumor Cells in Vivo with Great Precision. Chem. Mater. 2017, 29 (24), 10312–10325. https://doi.org/10.1021/acs.chemmater.7b03044.

(4) Hummel, S. G. digitalSELEX: A Novel Oligonucleotide Design Platform. PhD, Boston College, USA, 2023. https://dl.acm.org/doi/10.5555/AAI30312407.