A research article published in Science presents the first major analysis based on the Human Protein Atlas, including a detailed picture of the proteins that are linked to cancer, the number of proteins present in the bloodstream, and the targets for all approved drugs on the market.
The Human Protein Atlas, a major multinational research project supported by the Knut and Alice Wallenberg Foundation and launched in November 2014, has been set up to allow for a systematic exploration of the human proteome using antibody-based proteomics. This is accomplished by combining high-throughput generation of affinity-purified antibodies with protein profiling in a multitude of tissues and cells assembled in tissue microarrays. Confocal microscopy analysis using human cell lines is performed for more detailed protein localisation. The programme hosts the Human Protein Atlas portal with expression profiles of human proteins in tissues and cells.
The tissue-based analysis detected more than 90% of the putative protein-coding genes. The researchers used that approach to explore the human secretome, the membrane proteome, the druggable proteome, the cancer proteome, and the metabolic functions in 32 different tissues and organs. All the data are integrated in an interactive Web-based database. Based on 13 million annotated images, the database maps the distribution of proteins in all major tissues and organs in the human body.
As an open access resource, it is expected to help drive the development of new diagnostics and drugs, but also to provide basic insights in normal human biology.
Approximately 20,000 protein coding genes in humans have been analysed and classified using a combination of genomics, transcriptomics, proteomics, and antibody-based profiling. The study’s lead author is Mathias Uhlén, Professor of Microbiology at Stockholm's KTH Royal Institute of Technology and the director of the Human Protein Atlas programme.
The analysis shows that almost half of the protein-coding genes are expressed in a ubiquitous manner and thus found in all analysed tissues. Approximately 15% of the genes show an enriched expression in one or several tissues or organs, including well-known tissue-specific proteins, such as insulin and troponin. The testes have the most tissue-enriched proteins followed by the brain and the liver.
The analysis suggests that approximately 3,000 proteins are secreted from the cells and an additional 5,500 proteins are located to the membrane systems of the cells. "This is important information for the pharmaceutical industry. We show that 70% of the current targets for approved pharmaceutical drugs are either secreted or membrane-bound proteins," Uhlén says. "Interestingly, 30% of these protein targets are found in all analysed tissues and organs. This could help explain some side effects of drugs and thus might have consequences for future drug development."
The analysis also contains a study of the metabolic reactions occurring in different parts of the human body. The most specialised organ is the liver with a large number of chemical reactions not found in other parts of the human body.
The study has been carried out by researchers in Sweden at KTH Royal Institute of Technology, Uppsala University, Karolinska Institute, Chalmers University of Technology, Lund University, and Stockholm University. The main sites of the project are located at AlbaNova and SciLifeLab, KTH Royal Institute of Technology, Stockholm, Sweden, the Rudbeck Laboratory, Uppsala University, Uppsala, Sweden, and Lab Surgpath, Mumbai, India.
Uhlén M, Fagerberg L, Hallström BM, et al. Proteomics. Tissue-based map of the human proteome. Science 2015;347(6220):1260419. doi: 10.1126/science.1260419.