Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90% of the putative protein-coding genes. We used this 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 that allows exploration of individual proteins, as well as navigation of global expression patterns, in all major tissues and organs in the human body.

Global classification of the human proteins with regards to spatial expression patterns across organs and tissues is important for studies of human biology and disease.Here, we used a quantitative transcriptomics analysis (RNA-Seq) to classify the tissue-specific expression of genes across a representative set of all major human organs and tissues and combined this analysis with antibody-based profiling of the same tissues. To present the data, we launch a new version of the Human Protein Atlas that integrates RNA and protein expression data corresponding to ϳ80% of the human protein-coding genes with access to the primary data for both the RNA and the protein analysis on an individual gene level. We present a classification of all human protein-coding genes with regards to tissue-specificity and spatial expression pattern. The integrative human expression map can be used as a starting point to explore the molecular constituents of the human body. Molecular & Cellular Proteomics 13: 10.1074/mcp.M113.035600, 397-406, 2014.Central questions in human biology relate to how cells, tissues, and organs differ in the expression of genes and proteins and what consequences the global expression pattern has for the phenotype of various cells with different functions in the body. Therefore, the annotation of the human protein-coding genes with regards to the spatial, temporal, and functional space represents one of the greatest challenges in human biology (1). Important questions related to this are how many of the genes actually code for functional proteins, how many are expressed in a tissue-specific manner, and how many proteins have "housekeeping" functions and are therefore expressed in all cells? These questions have a major impact not only on efforts to try to understand human biology, but also for applied medical research, such as pharmaceutical drug development and biomarker discovery in the field of translational medicine.Several efforts have been initiated in the aftermath of the genome project to systematically annotate the putative protein-coding part of the human genome. Genome annotation efforts, such as Ensembl (2) and RefSeq (3), have provided an increasingly accurate map with at present ϳ20,000 proteincoding genes. Similarly, the ENCODE consortium has been launched to provide an integrated encyclopedia of DNA eleFrom the ‡Science for Life Laboratory, KTH -Royal Institute of Technology, SE-171 21 Stockholm, Sweden; §Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden; ¶Department

Cancer is one of the leading causes of death, and there is great interest in understanding the underlying molecular mechanisms involved in the pathogenesis and progression of individual tumors. We used systems-level approaches to analyze the genome-wide transcriptome of the protein-coding genes of 17 major cancer types with respect to clinical outcome. A general pattern emerged: Shorter patient survival was associated with up-regulation of genes involved in cell growth and with down-regulation of genes involved in cellular differentiation. Using genome-scale metabolic models, we show that cancer patients have widespread metabolic heterogeneity, highlighting the need for precise and personalized medicine for cancer treatment. All data are presented in an interactive open-access database (www.proteinatlas.org/pathology) to allow genome-wide exploration of the impact of individual proteins on clinical outcomes.

Resolving the spatial distribution of the human proteome at a subcellular level can greatly increase our understanding of human biology and disease. Here we present a comprehensive image-based map of subcellular protein distribution, the Cell Atlas, built by integrating transcriptomics and antibody-based immunofluorescence microscopy with validation by mass spectrometry. Mapping the in situ localization of 12,003 human proteins at a single-cell level to 30 subcellular structures enabled the definition of the proteomes of 13 major organelles. Exploration of the proteomes revealed single-cell variations in abundance or spatial distribution and localization of about half of the proteins to multiple compartments. This subcellular map can be used to refine existing protein-protein interaction networks and provides an important resource to deconvolute the highly complex architecture of the human cell.