Proteoform Barcode: An Intuitive Visualization Framework for Top-Down Proteomics

Top-down proteomics (TDP) advances biomedical research by providing a birds-eye view of proteoforms in cells, tissues, and biofluids. Thousands of proteoforms can be characterized using well-established TDP technologies, and potential proteoform biomarkers of diseases have been discovered. However, there is a lack of an easy and biologically informative approach to present the quantitative global TDP data. Here, we present proteoform barcode as a straightforward visualization approach that simultaneously displays proteoform abundance and their associated Gene Ontology (GO) biological processes, converting a list of proteoforms to a biologically informative image. The proteoform barcode allows 1) a global view of proteoforms (i.e., relative abundance and functional information) in complex biological systems (i.e., bacteria, yeast, human cells, and human plasma) and 2) the accurate distinction of samples in diverse biological conditions (i.e., control and disease) assisted by machine learning approaches. The proteoform barcode, assisted by the random forest model, accurately separated the human plasma samples of healthy controls and early-stage breast cancer. The data demonstrates the high potential of the proteoform barcode-based approach for early diagnosis of diseases in an easy and biologically informative manner.