The Human Protein Atlas The Tissue Atlas The Single Cell Type Atlas The Pathology Atlas The Brain Atlas The Blood Atlas The Cell Atlas Background and History

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.
The Human Protein Atlas consists of six separate parts, each focusing on a particular aspect of the genome-wide analysis of the human proteins:

The Tissue Atlas, showing the distribution of the proteins across all major tissues and organs in the human body
The Single Cell Type Atlas, showing expression of protein-coding genes in single human cell types
The Pathology Atlas, showing the impact of protein levels for the survival of patients with cancer
The Blood Atlas, describing proteins detected in the blood cell types and proteins secreted by human tissues
The Brain Atlas, exploring the distribution of proteins in various regions of the mammalian brain
The Cell Atlas, showing the subcellular localization of proteins in single cells

The Human Protein Atlas program has already contributed to several thousands of publications in the field of human biology and disease and it is selected by the organization ELIXIR (www.elixir-europe.org) as a European core resource due to its fundamental importance for a wider life science community. The Human Protein Atlas consortium is mainly funded by the Knut and Alice Wallenberg Foundation.

Uhlén M et al., Tissue-based map of the human proteome. Science (2015)
PubMed: 25613900 DOI: 10.1126/science.1260419

Thul PJ et al., A subcellular map of the human proteome. Science. (2017)
PubMed: 28495876 DOI: 10.1126/science.aal3321

Uhlen M et al., A pathology atlas of the human cancer transcriptome. Science. (2017)
PubMed: 28818916 DOI: 10.1126/science.aan2507

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.

Example:

MYL7
Myosin, light chain 7, regulatory.

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.

Example:

TSPY2
Testis specific protein, Y-linked 2.

Selective nuclear expression of spermatogonia at the protein level, enriched in spermatogonia at the mRNA level.

TSPY2

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.

Example:

MKI67
Marker of proliferation Ki-67.

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.

Example:

NECAB1
N-terminal EF-hand calcium binding protein 1.

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.

NECAB1

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.

Example:

FN1
The cellular glycoprotein FN1.

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.

FN1

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.

Example:

CCNB1
Cyclin B1.

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:

Version	Year released	Feature
2	2006	Inclusion of cell-line data and confocal images showing subcellular localizations.
3	2007	A new search function that allowed advanced query based searches was included.
4	2008	The overall database structure was shifted from a previously antibody-centric structure, to a gene-centric structure in order to include information on all genes predicted by Ensembl.
7	2010	A major restructure accompanying the introduction of the concept of annotated protein expression for paired antibodies (two independent antibodies directed against different, non-overlapping epitopes on the same protein).
12	2013	The protein atlas database was complemented with transcriptomics profiles from 27 normal tissues, and the format with four sub-atlases was introduced.
13	2014	An analysis of all major organ and tissues in the human body using transcriptomics and antibody-based profiling was included. The results were summarized on interactive knowledge-pages divided into 7 human proteomes and 27 tissues and organs.
14	2015	A new mouse brain atlas was introduced.
15	2016	Inclusion of RNA-seq data from the Genotype-Tissue Expression (GTEx) consortium.
16	2016	A new Cell Atlas was launched with subcellular localization corresponding to over 12,000 protein-coding genes, together with a new approach for visualization of antibody validation and the inclusion of transcriptomics data from the FANTOM5 program.
17	2017	The Pathology Atlas was launched, where a systems-level approach based on genome-wide transcriptomics data and clinical meta data of almost 8000 patients was used in order to analyze the proteome of 17 major cancer types.
19	2019	Three new Atlases were introduced; a Blood Atlas, a Brain Atlas and a Metabolic Atlas.