Location Proteomics: Systematic Determination of Protein Subcellular Location

Proteomics seeks the systematic and comprehensive understanding of all aspects of proteins, and location proteomics is the relatively new subfield of proteomics concerned with the location of proteins within cells. This review provides a guide to the widening selection of methods for studying location proteomics and integrating the results into systems biology. Automated and objective methods for determining protein subcellular location have been described based on extracting numerical features from fluorescence microscope images and applying machine learning approaches to them. Systems to recognize all major protein subcellular location patterns in both two-dimensional and three-dimensional HeLa cell images with high accuracy (over 95% and 98%, respectively) have been built. The feasibility of objectively grouping proteins into subcellular location families, and in the process of discovering new subcellular patterns, has been demonstrated using cluster analysis of images from a library of randomly tagged protein clones. Generative models can be built to effectively capture and communicate the patterns in these families. While automated methods for high-resolution determination of subcellular location are now available, the task of applying these methods to all expressed proteins in many different cell types under many conditions represents a very significant challenge.