Quantifying metabolites using structure-switching aptamers coupled to DNA sequencing

Area of Science:

• Biochemistry
• Molecular Biology
• Genomics

Background:

• Metabolomics is crucial for understanding biological processes.
• Current metabolite quantification methods face challenges in specificity and multiplexing.
• There is a need for innovative techniques to analyze complex metabolic profiles.

Purpose of the Study:

• To introduce a novel method, small-molecule sequencing (smol-seq), for metabolite quantification.
• To demonstrate the utility of structure-switching aptamers (SSAs) in conjunction with DNA sequencing for metabolomics.
• To enable high-throughput and specific measurement of metabolites.

Main Methods:

• Developed structure-switching aptamers (SSAs) designed to bind specific target metabolites.
• Utilized a mechanism where SSA binding releases a unique DNA barcode.
• Employed DNA sequencing to read out the released barcodes, correlating them to metabolite concentrations.

Main Results:

• Demonstrated high specificity of SSAs for individual metabolite detection.
• Showcased the ability to multiplex SSAs for simultaneous detection of multiple metabolites.
• Successfully quantified metabolite levels by sequencing the released DNA barcodes.

Conclusions:

• smol-seq offers a powerful new approach for metabolite quantification in complex biological samples.
• The combination of SSAs and DNA sequencing enhances specificity and multiplexing capabilities in metabolomics.
• This method advances the field of metabolomics by providing a sensitive and scalable tool for metabolite analysis.