The Human Protein Atlas
The Human Protein Atlas is a Swedish-based program initiated in 2003 with the aim to map all the human proteins in cells, tissues and organs using an integration of various omics technologies, including antibody-based imaging, mass spectrometry-based proteomics, transcriptomics and systems biology. All the data in the knowledge resource is open access to allow scientists both in academia and industry to freely access the data for exploration of the human proteome.
Uhlén M et al., Tissue-based map of the human proteome. Science (2015)
The full publication list is available here.
The Tissue Atlas
The Tissue Atlas shows the expression and localization of human proteins across tissues and organs, based on deep sequencing of RNA (RNA-seq) from 37 major different normal tissue types and immunohistochemistry on tissue microarrays containing 44 different tissue types. Altogether 76 different cell types, corresponding to 44 normal human tissue types covering all major parts of the human body, have been analyzed manually and the data is presented as histology-based annotation of protein expression levels. The antibody-based protein profiles are qualitative and describe the spatial distribution, cell type specificity and the rough relative abundance of proteins in these tissues, whereas the mRNA data provide quantitative data on the average gene expression within an entire tissue. For each gene, the immunohistochemical staining profile is matched with mRNA data and gene/protein characterization data to yield an "annotated protein expression" profile.
Selective cytoplasmic expression in cardiomyocytes at the protein level, tissue enriched in heart muscle at the mRNA level.
The Single Cell Type Atlas
The Cell Type Atlas shows single cell RNA sequencing (scRNAseq) data from 13 different human tissues, together with immunohistochemically stained tissue sections visualizing the corresponding spatial protein expression patterns. The scRNAseq analysis was based on publicly available genome-wide expression data and comprises all protein-coding genes in 192 individual single cell clusters. These clusters have been annotated as 51 cell types using >500 well-known cell type-specific markers. The genes expressed in each of the cell types can be explored in interactive UMAP plots and bar charts, with links to corresponding immunohistochemical stainings in human tissues.
Selective nuclear expression of spermatogonia at the protein level, enriched in spermatogonia at the mRNA level.
The Pathology Atlas
The Human Pathology Atlas is based on a systems-based analysis of the transcriptome of 17 main cancer types using data from 8000 patients. In addition, we show a new concept to present patient survival data, called Interactive Survival Scatter plots, and in the atlas, we present more than 400,000 plots. A national supercomputer center were used to analyze more than 2.5 petabytes of underlying publicly available data from the Cancer Genome Atlas (TCGA) to generate more than 900,000 survival plots describing the consequence of RNA and protein levels on clinical survival. The Pathology Atlas also contains 5 million pathology-based images generated by the Human Protein Atlas consortium. The research reports several important findings related to cancer biology and treatment. Firstly, many genes are differentially expressed in cancers, and a large proportion of these genes have an impact on overall patient survival. The research also showed that gene expression patterns of individual tumors varied considerably, and could exceed the variation observed between different cancer types. Shorter patient survival was generally associated with up-regulation of genes involved in mitosis and cell growth, and down-regulation of genes involved in cellular differentiation. The data allowed for generation of personalized genome-scale metabolic models for cancer patients to identify key genes involved in tumor growth.
Nuclear expression in varying fractions of tumor cells in all cancer types at protein level and expressed in all cancers at mRNA level. High expression of this gene is associated with unfavorable prognosis in renal, liver and pancreatic cancer.
The Brain Atlas
The Brain Atlas explores the protein expression in the mammalian brain by integration of data from three mammalian species (human, pig and mouse). Transcriptomics data is combined with antibody-based protein localization in human samples and whole mouse brain. Protein-coding human genes (and one-to-one orthologues in pig and mouse) is provided with a brain-centric summary page, showing available expression data (mRNA) for brain samples grouped into 10 main brain regions, as well as data for pituitary gland, retina, corpus callosum and spinal cord. Series of sections, representing the whole mouse brain, analyzed for 300 genes are available as large 100 megapixel immunofluorescence images with microscopic resolution to explore the protein location in mouse brain (also summarized into 127 regions of interest). A selection of human localization data is also imported/linked from the Tissue Atlas and summarized on the Brain Atlas.
Subsets of neurons show distinct somato-dendritic immunoreactivity throughout the brain. The image show protein location in subsets of neurons in the hippocampus of mouse brain.
The Blood Atlas
The Blood Atlas contributes with data regarding the cell types and proteome of human blood. Transcriptomics data from 18 single blood cell types isolated by cell sorting, including various B- and T-cells, monocytes, granulocytes and dendritic cells, is provided. The blood proteome is represented by data on concentration of blood proteins determined by mass spectrometry-based proteomics and/or antibody-based immune assays. In addition, a categorisation of the human secretome is presented, where the human predicted secreted proteins have been annotated in an attempt to determine which genes are actively secreted to human blood and which have more local functions in compartments such as the digestive system, brain or reproductive tissues.
Fibronectin is a glycoprotein that exists both as a soluble plasma fibronectin produced by liver hepatocytes and being the major protein component of blood plasma, and as an insoluble cellular fibronectin secreted primarily by fibroblasts and constituting the major component of the extracellular matrix. The image shows the insoluble cellular form in the extracellular matrix of rectum.
The Cell Atlas
The Cell Atlas provides high-resolution insights in the spatial distribution of proteins within cells. First, it contains mRNA expression profiles for a diverse panel of human-derived cell lines (n=69) representing different cell types, tissues and organs in the human body. Second, the Cell Atlas contains high-resolution, multi-colour immunofluorescence images of cells that detail the subcellular distribution pattern of proteins encoded by 12813 genes (65% of the human protein-coding genes). By default, U-2 OS and 2 other cell lines, selected based on gene expression, are probed with each antibody. The cells are stained in a standardized way where the antibody of interest is visualized in green, microtubules red, the endoplasmic reticulum yellow, and the nucleus counterstained in blue. The images are manually annotated in terms of spatial distribution to 35 different subcellular structures, representing 14 major organelles. The annotated locations for each protein are classified as main and additional, and assigned a reliability score.
The protein localizes to the cytosol in human and mouse cells, and is expressed in a cell cycle-dependent manner. The location has been validated by siRNA mediated gene silencing, analysis of GFP-tagged protein and independent antibodies.
Background and History
The Human Protein Atlas project was initiated in 2003 by funding from the Knut and Alice Wallenberg foundation. Primarily based in Sweden, the Human Protein Atlas project involves the joint efforts of the Royal Institute of Technology in Stockholm, Uppsala University, Uppsala Akademiska University Hospital, and more recently also Science for Life Laboratory based in both Uppsala and Stockholm. Formal collaborations are with groups in India, South Korea, Japan, China, Germany, France, Switzerland, USA, Canada, Denmark, Finland, The Netherlands, Spain, and Italy.
The pathologists and staff at the Pathology Clinic, Uppsala University Hospital, Uppsala, Sweden, are greatly acknowledged for all efforts regarding handling and diagnostics of the tissues used in the Human Protein Atlas. Dr Sanjay Navani and Lab Surgpath, Mumbai, India, are also acknowledged for the major contribution regarding annotation of immunohistochemically stained normal and cancer tissues.
The first version of the Human Protein Atlas website was launched in 2005 and consisted of protein expression data based on approximately 700 antibodies. Since then, each new release has included more data and new functionalities and features to the website.
Important additions include: