Membrane marker selection for segmenting single cell spatial proteomics data

The ability to profile spatial proteomics at the single cell level enables the study of cell types, their spatial distribution, and interactions in several tissues and conditions. Current methods for cell segmentation in such studies rely on known membrane or cell boundary markers. However, for many tissues, an optimal set of markers is not known, and even within a tissue, different cell types may express different markers. Here we present RAMCES, a method that uses a convolutional neural network to learn the optimal markers for a new sample and outputs a weighted combination of the selected markers for segmentation. Testing RAMCES on several existing datasets indicates that it correctly identifies cell boundary markers, improving on methods that rely on a single marker or those that extend nuclei segmentations. Application to new spatial proteomics data demonstrates its usefulness for accurately assigning cell types based on the proteins expressed in segmented cells.