Plasma exosome profiling of cancer patients by a next generation systems biology approach
| Autor: | George Poste, Adam Stark, Valeriy Domenyuk, Janet E. Duncan, Joachim Schorr, David D. Halbert, Nianqing Xiao, Sonal S. Tonapi, Jie Wang, Heather A. O'Neill, John Quackenbush, Donald A. Berry, Teresa T. Tinder, Zhenyu Zhong, Andrew Hunter, Mark R. Miglarese, Xixi Wei, Tassilo Hornung, Günter Mayer, David Spetzler, Michael Famulok |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Systems biology Breast Neoplasms Bioinformatics Exosomes Exosome Article 03 medical and health sciences Breast cancer Area under curve Biomarkers Tumor Medicine Humans Multidisciplinary business.industry Systems Biology SELEX Aptamer Technique High-Throughput Nucleotide Sequencing Sequence Analysis DNA medicine.disease Microvesicles 030104 developmental biology Oligodeoxyribonucleotides Patient classification Area Under Curve Female business |
| Zdroj: | Scientific Reports |
| Popis: | 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 ~1011 ssODNs for those associating with exosomes from breast cancer patients or controls. The resulting 106 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. |
| Databáze: | OpenAIRE |
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