Identifying tumor cells at the single cell level

Abstract 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. The single cell sequencing technology enables an effective molecular characterization of single cells within the tumor. This technology can help deconvolute heterogeneous tumor samples and thus revolutionize personalized medicine. However, 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. One of the critical cell type annotation challenges is identification of tumor cells within single cell or spatial sequencing experiments.This is a critical limiting step for a multitude of research, clinical, and commercial applications. A reliable method addressing that challenge is a prerequisite for automatic annotation of histopathological data, profiled using multichannel immunofluorescence or spatial sequencing. Here, we propose Ikarus, a machine learning pipeline aimed at distinguishing tumor cells from normal cells at the single cell level. We have tested ikarus on multiple single cell datasets to ascertain that it achieves high sensitivity and specificity in multiple experimental contexts.