Identifying tumor cells at the single cell level

Tumors are highly complex tissues composed of cancerous cells, surrounded by a heterogeneous cellular microenvironment. Tumor response to treatments is governed by an interaction of cancer cell intrinsic factors with external influences of the tumor microenvironment. Disentangling the heterogeneity within a tumor is a crucial step in developing and utilization of effective cancer therapies. Single cell sequencing has the potential to revolutionize personalized medicine. In cancer therapy it enables an effective characterization of the complete heterogeneity within the tumor. A governing challenge in cancer single cell analysis is cell annotation, the assignment of a particular cell type or a cell state to each sequenced cell. We propose Ikarus, a machine learning pipeline aimed at solving a perceived simple problem, distinguishing tumor cells from normal cells at the single cell level. Automatic characterization of tumor cells is a critical limiting step for a multitude of research, clinical, and commercial applications. Automatic characterization of tumor cells would expedite neoantigen prediction, automatic characterization of tumor cell states, it would greatly facilitate cancer biomarker discovery. Such a tool can be used for automatic annotation of histopathological data, profiled using multichannel immunofluorescence or spatial sequencing. We have tested ikarus on multiple single cell datasets to ascertain that it achieves high sensitivity and specificity in multiple experimental contexts.