Vislocas: Vision transformers for identifying protein subcellular mis-localization signatures of different cancer subtypes from immunohistochemistry images

Abstract

Proteins must be sorted to specific subcellular compartments to perform their functions. Abnormal protein subcellular localizations are related to many diseases. Although many efforts have been made in predicting protein subcellular localization from various static information, including sequences, structures and interactions, such static information cannot predict protein mis-localization events in diseases. On the contrary, the IHC (immunohistochemistry) images, which have been widely applied in clinical diagnosis, contains information that can be used to find protein mis-localization events in disease states. In this study, we create the Vislocas method, which is capable of finding mis-localized proteins from IHC images as markers of cancer subtypes. By combining CNNs and vision transformer encoders, Vislocas can automatically extract image features at both global and local level. Vislocas can be trained with full-sized IHC images from scratch. It is the first attempt to create an end-to-end IHC image-based protein subcellular location predictor. Vislocas achieved comparable or better performances than state-of-the-art methods. We applied Vislocas to find significant protein mis-localization events in different subtypes of glioma, melanoma and skin cancer. The mis-localized proteins, which were found purely from IHC images by Vislocas, are in consistency with clinical or experimental results in literatures. All codes of Vislocas have been deposited in a Github repository (https://github.com/JingwenWen99/Vislocas). All datasets of Vislocas have been deposited in Zenodo (https://zenodo.org/records/10632698).