Abstract
Tumors are complex tissues of cancerous cells surrounded by a heterogeneous cellular microenvironment with which they interact. Single-cell sequencing enables molecular characterization of single cells within the tumor. However, cell annotation-the assignment of cell type or cell state to each sequenced cell-is a challenge, especially identifying tumor cells within single-cell or spatial sequencing experiments. Here, we propose ikarus, a machine learning pipeline aimed at distinguishing tumor cells from normal cells at the single-cell level. We test ikarus on multiple single-cell datasets, showing that it achieves high sensitivity and specificity in multiple experimental contexts.