Selection of Aptamers for Ovarian Cancer Biomarkers Informed by Next-Generation Sequencing and Bioinformatics
Characterized by late clinical presentation, significant co-morbidity and poor long-term survival, epithelial ovarian cancer (EOC) remains a serious medical concern to women. We have used three variants of the aptamer selection (SELEX) process to identify new functional oligonucleotides that recognize ovarian cancer biomarkers. Cell-SELEX has been used to select aptamers for cell-associated mesothelin and MUC16, two proteins implicated in metastasis and immune suppression. CE-SELEX was used to select aptamers for HE4, an informative serum marker. Finally, we have developed a novel “one-pot” selection method in which the gold standard ovarian cancer biomarker, CA25, is the target. In each case, the selection process concluded with the interrogation of the selected DNA pool by high-throughput sequencing. This sequencing process yields significantly more insight on the selection process than the conventional sequencing that has traditionally been used at the end of the SELEX process. We have developed a set of bioinformatics tools that enable the most enriched aptamer candidates to be identified. Affinity probe capillary electrophoresis, fluorescence anisotropy and label-free immunoassay platforms are currently being used to assess the affinity of the selected aptamers for their targets. We acknowledge support from the National Cancer Institute.
Whelan, Rebecca. “Selection of Aptamers for Ovarian Cancer Biomarkers Informed by Next-Generation Sequencing and Bioinformatics." Presentation at the 2015 Pittcon Conference & Expo, New Orleans, LA, March 8-12, 2015.
Chemistry and Biochemistry
Bioanalytical, Bioinformatics, Capillary Electrophoresis, Nucleic Acids