Combining Machine Learning and Nanofluidic Technology To Diagnose Pancreatic Cancer Using Exosomes

被引:195
作者
Ko, Jina [1 ]
Bhagwat, Neha [3 ]
Yee, Stephanie S. [1 ,4 ]
Ortiz, Natalia
Sahmoud, Amine [3 ]
Black, Taylor [3 ]
Aiello, Nicole M. [3 ]
McKenzie, Lydie [4 ]
O'Hara, Mark [4 ]
Redlinger, Colleen [5 ]
Romeo, Janae [5 ]
Carpenter, Erica L. [4 ]
Stanger, Ben Z. [3 ]
Issadore, David [1 ,2 ]
机构
[1] Univ Penn, Dept Bioengn, Sch Engn & Appl Sci, Philadelphia, PA 19104 USA
[2] Univ Penn, Dept Elect & Syst Engn, Sch Engn & Appl Sci, Philadelphia, PA 19104 USA
[3] Univ Penn, Div Gastroenterol, Perelman Sch Med, Philadelphia, PA 19104 USA
[4] Univ Penn, Div Hematol Oncol, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA
[5] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA
关键词
cancer diagnostics; exosomes; nanofluidics; machine learning pancreatic cancer; CIRCULATING TUMOR-CELLS; GENE-EXPRESSION; IMMUNOMAGNETIC ISOLATION; EXTRACELLULAR VESICLES; MICROVESICLES; PROFILES; TRAP;
D O I
10.1021/acsnano.7b05503
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Circulating exosomes contain a wealth of proteomic and genetic information, presenting an enormous opportunity in cancer diagnostics. While microfluidic approaches have been used to successfully isolate cells from complex samples, scaling these approaches for exosome isolation has been limited by the low throughput and susceptibility to clogging of nanofluidics. Moreover, the analysis of exosomal biomarkers is confounded by substantial heterogeneity between patients and within a tumor itself. To address these challenges, we developed a multichannel nanofluidic system to analyze crude clinical samples. Using this platform, we isolated exosomes from healthy and diseased murine and clinical cohorts, profiled the RNA cargo inside of these exosomes, and applied a machine learning algorithm to generate predictive panels that could identify samples derived from heterogeneous cancer-bearing individuals. Using this approach, we classified cancer and precancer mice from healthy controls, as well as pancreatic cancer patients from healthy controls, in blinded studies.
引用
收藏
页码:11182 / 11193
页数:12
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