Deriving spatial features from in situ proteomics imaging to enhance cancer survival analysis.

MOTIVATION: Spatial proteomics data have been used to map cell states and improve our understanding of tissue organization. More recently, these methods have been extended to study the impact of such organization on disease progression and patient survival. However, to date, the majority of supervised learning methods utilizing these data types did not take full advantage of the spatial information, impacting their performance and utilization. RESULTS: Taking inspiration from ecology and epidemiology, we developed novel spatial feature extraction methods for use with spatial proteomics data. We used these features to learn prediction models for cancer patient survival. As we show, using the spatial features led to consistent improvement over prior methods that used the spatial proteomics data for the same task. In addition, feature importance analysis revealed new insights about the cell interactions that contribute to patient survival. AVAILABILITY AND IMPLEMENTATION: The code for this work can be found at gitlab.com/enable-medicine-public/spatsurv.

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.