Construction of an Array of Biosensors Using Density Evolution for MicroRNA Monitoring

Muralikrishnna G. Sethuraman, Megan A. McSweeney, Mark P. Styczynski, Faramarz Fekri

Abstract: Monitoring the levels of biomarkers for diagnostic applications has significant potential for impacts on patient care, but the measurement of all relevant biomarkers for a given set of conditions is often too expensive or unwieldy to be feasible at scale. Here, we propose a novel computational method for detecting changes in the levels of multiple target molecules from a complex sample via a small, cost-effective group of biosensors. We use the framework of density evolution (DE), a technique commonly used in the design of linear error-correcting codes for transmission over noisy channels, to develop an approach for localizing changes to a small subset of input signals based on a few simple output signals. As a biologically relevant testbed, we sought to detect the changes in the levels of multiple different microRNAs (miRNAs), which are nucleic acid molecules that are being increasingly studied and used as biomarkers. We accomplished this via the use of a class of molecules called “toehold switches” to create biosensors each capable of detecting multiple different miRNA sequences via a single output, with an overlap in sensitivity patterns between the different biosensors. A small number of these sensors were then used for inference of miRNA profiles. We demonstrate the potential utility of our approach with real data. Experimental results indicate the promising outcomes regarding the effectiveness of our method in detecting changes in miRNA concentrations.

External IDs:doi:10.1109/tmbmc.2025.3547892