Introduction

Improved technologies capable of characterizing system-wide changes associated with complex diseases will be required to be able to detect millions of proteins and their isoforms as well as multi-molecular complexes. We present a method for developing aptamer libraries using blood plasma exosomes that provides unprecedented system-wide coverage of native exosomal complexes.

Summary

• Serial enrichment on individual plasma exosome samples promotes evolution of aptamer libraries to dramatically improve identification of PR +/ER+/HER2- patients
• 100% of independent PR+/ER+/HER2- patients were correctly identified using the evolved library
• The evolved library also maintained the ability to detect other breast cancer subtypes (ROC AUC = 0.924)
• This technology is uniquely suited for profiling complex systems and phenotypes because it is based on physical evolution at the population level, NOT algorithm training
• More libraries for other subtypes are currently being built
• Basic research on feasibility of aptamer library enrichment directly on blood plasma and specificity of enriched aptamer library binding exosomal proteins was shown in Domenyuk et al. Plasma Exosome Profiling of Cancer Patients by a Next Generation Systems Biology Approach. Scientific reports 7, 2017, doi:10.1038/srep42741.