Plasma Exosome Profiling of Cancer Patients by a Next Generation Systems Biology Approach

Valeriy Domenyuk, Zhenyu Zhong, Adam Stark, Nianqing Xiao, Heather A. O'Neill, Xixi Wei, Jie Wang, Teresa T. Tinder, Sonal Tonapi, Janet Duncan, Tassilo Hornung, Andrew Hunter, Mark R. Miglarese, Joachim Schorr, David D. Halbert, John Quackenbush, George Poste, Donald A. Berry, Günter Mayer, Michael FamulokDavid Spetzler

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Technologies capable of characterizing the full breadth of cellular systems need to be able to measure millions of proteins, isoforms, and complexes simultaneously. We describe an approach that fulfils this criterion: Adaptive Dynamic Artificial Poly-ligand Targeting (ADAPT). ADAPT employs an enriched library of single-stranded oligodeoxynucleotides (ssODNs) to profile complex biological samples, thus achieving an unprecedented coverage of system-wide, native biomolecules. We used ADAPT as a highly specific profiling tool that distinguishes women with or without breast cancer based on circulating exosomes in their blood. To develop ADAPT, we enriched a library of ∼10 11 ssODNs for those associating with exosomes from breast cancer patients or controls. The resulting 10 6 enriched ssODNs were then profiled against plasma from independent groups of healthy and breast cancer-positive women. ssODN-mediated affinity purification and mass spectrometry identified low-abundance exosome-associated proteins and protein complexes, some with known significance in both normal homeostasis and disease. Sequencing of the recovered ssODNs provided quantitative measures that were used to build highly accurate multi-analyte signatures for patient classification. Probing plasma from 500 subjects with a smaller subset of 2000 resynthesized ssODNs stratified healthy, breast biopsy-negative, and -positive women. An AUC of 0.73 was obtained when comparing healthy donors with biopsy-positive patients.

Original languageEnglish (US)
Article number42741
JournalScientific reports
Volume7
DOIs
StatePublished - Feb 20 2017

ASJC Scopus subject areas

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    Domenyuk, V., Zhong, Z., Stark, A., Xiao, N., O'Neill, H. A., Wei, X., Wang, J., Tinder, T. T., Tonapi, S., Duncan, J., Hornung, T., Hunter, A., Miglarese, M. R., Schorr, J., Halbert, D. D., Quackenbush, J., Poste, G., Berry, D. A., Mayer, G., ... Spetzler, D. (2017). Plasma Exosome Profiling of Cancer Patients by a Next Generation Systems Biology Approach. Scientific reports, 7, [42741]. https://doi.org/10.1038/srep42741