Integrative Analysis and Machine Learning Based Characterization of Single Circulating Tumor Cells
Arvind Iyer, Krishan Gupta, Shreya Sharma, Kishore Hari, Yi Lee, Neevan Ramalingam, Neevan Ramalingam, Yoon Sim Yap, Jay West, Ali Asgar S. Bhagat, Balaram Vishnu Subramani, Burhanuddin Sabuwala, Tuan Zea Tan, Jean Paul Thiery, Mohit Kumar Jolly, Naveen Ramalingam, Naveen Ramalingam, Debarka Sengupta
Abstract
We collated publicly available single-cell expression profiles of circulating tumor cells (CTCs) and showed that CTCs across cancers lie on a near-perfect continuum of epithelial to mesenchymal (EMT) transition. Integrative analysis of CTC transcriptomes also highlighted the inverse gene expression pattern between PD-L1 and MHC, which is implicated in cancer immunotherapy. We used the CTCs expression profiles in tandem with publicly available peripheral blood mononuclear cell (PBMC) transcriptomes to train a classifier that accurately recognizes CTCs of diverse phenotype. Further, we used this classifier to validate circulating breast tumor cells captured using a newly developed microfluidic system for label-free enrichment of CTCs.