Human Protein Atlas

The Human Protein Atlas (HPA) is a

Swedish-based program started in 2003 with
the aim to map all the human proteins in cells,
tissues and organs using 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. In December 2022, version 22 was
launched where two new sections, a Human
Disease Blood Atlas and a Structure resource
section, were introduced, both relying heavily
on AI-based prediction modelling and
machine learning.
The resource now includes twelve separate
sections with complementary information
about all human proteins. All data has been
updated on the approximately 5 million
individual web pages. The Human Protein
Atlas program has already contributed to
several thousands of publications in the field
of human biology and disease and was
selected by the organization ELIXIR as a
European core resource due to its
fundamental importance for a wider life
science community. The HPA consortium is
funded by the Knut and Alice Wallenberg
Foundation.
Human Protein Atlas
Content
Description The Human Protein Atlas portal is a
publicly available database with
millions of high-resolution images
showing the spatial distribution of
proteins in normal human tissues and
different cancer types, as well the sub
cellular localisation in single cells.
Organisms Human
Contact
Research center KTH, UU, SciLifeLab, Sweden
Primary citation Uhlén M, et al. (January 2015).
"Proteomics. Tissue-based map of
the human proteome". Science. 347
(6220): 1260419.
doi:10.1126/science.1260419 (https://
doi.org/10.1126%2Fscience.126041
9). PMID 25613900 (https://pubmed.
ncbi.nlm.nih.gov/25613900).
S2CID 802377 (https://api.semanticsc
holar.org/CorpusID:802377).
Access
Website www.proteinatlas.org (http://www.prot
einatlas.org)

Twelve sections Download URL www.proteinatlas.org/about/download

(http://www.proteinatlas.org/about/do
The Human Protein Atlas consists of twelve wnload)
sections: Tools
Web Advanced search, bulk
The Tissue[1] section of the Human
Protein Atlas focuses on the retrieval/download
expression profiles in human tissues Miscellaneous
of genes both on the mRNA and
protein level. The protein expression Versioning Yes
data from 44 normal human tissue Data release 12 months
types is derived from antibody-based frequency
protein profiling using
immunohistochemistry. All underlying Version 22
images of immunohistochemistry
stained normal tissues are available Curation policy Yes – manual
together with knowledge-based Bookmarkable Yes – both individual protein entries
annotation of protein expression entities and searches
levels.
The Brain[2] section provides comprehensive spatial profiling of the brain, including
overview of protein expression in the mammalian brain based on integration of data from
human, pig and mouse. Transcriptomics data combined with affinity-based protein in situ
localization down to single cell detail is available in this brain-centric sub atlas of the Human
Protein Atlas. The data presented are for human genes and their one-to-one orthologues in
pig and mouse. Gene summary pages provide the hierarchical expression landscape form
13 main regions of the brain to individual nuclei and subfields for every protein coding gene.
For selected proteins, high content images are available to explore the cellular and
subcellular protein distribution. In addition, the Brain section contains lists of genes with
elevated expression in one or a group of regions to help the user identify unique protein
expression profiles linked to physiology and function.
The Single Cell Type[3] section contains information based on single cell RNA sequencing
(scRNAseq) data from 25 human tissues and peripheral blood mononuclear cells (PBMCs),
together with in-house generated 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 444 individual cell type clusters corresponding to 15 different cell type groups. A
specificity and distribution classification was performed to determine the number of genes
elevated in these single cell types, and the number of genes detected in one, several or all
cell types, respectively. 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.
The Tissue Cell Type section contains cell type expression specificity predictions for all
human protein coding genes, generated using integrated network analysis of publicly
available bulk RNAseq data. A specificity classification is used to predict which genes are
enriched in each constituent cell type within an individual tissue. The data can be explored
on a tissue-by-tissue basis, together with in-house generated immunohistochemically
stained tissue sections. In addition, a core cell type analysis focuses on the cell types found
in all, or the majority, of the profiled tissues, e.g., endothelial cells or macrophages. Here,
genes with predicted specificity in these core cell types in multiple tissues are detailed.
The Pathology[4] section contains information based on mRNA and protein expression data
from 17 different forms of human cancer, together with millions of in-house generated
immunohistochemically stained tissue sections images and Kaplan-Meier plots showing the
correlation between mRNA expression of each human protein gene and cancer patient
survival.
The Immune Cell[5] section contains single cell information on genome-wide RNA
expression profiles of human protein-coding genes covering various B- and T-cells,
monocytes, granulocytes and dendritic cells. The transcriptomics analysis covers 18 cell
types isolated with cell sorting and includes classification based on specificity, distribution
and expression cluster across all immune cells.
The Blood Proteins[6] section presents estimated plasma concentrations of the proteins
detected in human blood from mass spectrometry-based proteomics studies, published
immune assay data and a longitudinal study based on proximity extension assay (PEA).
Further, an analysis of the “human secretome” is presented including annotation of the
genes predicted to be actively secreted to human blood, as well as to other compartments or
organ systems of the human body such as the digestive tract or the brain.
 The Subcellular[7] section of the Human Protein Atlas provides high-resolution insights into
the expression and spatiotemporal distribution of proteins encoded by 13041 genes (65% of
the human protein-coding genes). For each gene, the subcellular distribution of the protein
has been investigated by immunofluorescence (ICC-IF) and confocal microscopy in up to
three different cell lines, selected from a subset of 36 of the cell lines found in the Cell Line
Section. Upon image analysis, the subcellular localization of the protein has been classified
into one or more of 35 different organelles and fine subcellular structures. In addition, the
section includes an annotation of genes that display single-cell variation in protein
expression levels and/or subcellular distribution, as well as an extended analysis of cell
cycle dependency of such variations.
The Cell Line section contains information on genome-wide RNA expression profiles of
human protein-coding genes in 69 human cell lines. The transcriptomics analysis includes
classification based on specificity, distribution and expression cluster analysis across all cell
lines.
The Metabolic[8] section enables exploration of protein function and tissue-specific gene
expression in the context of the most curated human metabolic network. For proteins
involved in metabolism, a metabolic summary is provided that describes the metabolic
subsystems/pathways, cellular compartments, and number of reactions associated with the
protein. Over 120 manually curated metabolic pathway maps facilitate the visualization of
each protein's participation in different metabolic processes. Each pathway map is
accompanied by a heatmap detailing the mRNA levels across 256 different tissue types for
all proteins involved in the metabolic pathway. Further details and full cellular compartment
maps are available at metabolicatlas.org.[9]
The Disease section contains information on protein levels in blood in patients with different
diseases and highlights proteins associated with these diseases using differential
expression analysis and a disease prediction strategy based on machine-learning.
The Structure section contains information about the three-dimensional structure of human
proteins.

Additional features
In addition to the twelve sections of HPA, exploring gene and protein expression, there are various features
available at the HPA website to assist the research community, including integrated external resources, such
as Metabolic Atlas, educational material and free downloadable data.

The “Learn” section of HPA includes educational resources, including information regarding
antibody-based applications and techniques, a histology dictionary and educational 3D
videos. The dictionary is an interactive tool for free full-screen exploration of whole slide
images of normal human organs and tissues, cancer tissues and cell structures, guided with
detailed annotations of all major structural elements. Educational videos have been
produced by HPA, depicting the exploration of the human body in 3D, using antibody-based
profiling of tissues and light sheet microscopy. The movies are available at the HPA website
as well as on a YouTube channel.
Datasets used in HPA are made freely available to encourage further studies within the
research community. Access to the extensive datasets is given through the downloadable
data page of HPA, wherein 29 different downloadable files are available, containing
genome‐wide data across various assays.

History
The Human Protein Atlas program was started in 2003 and funded by the non-profit organization Knut and
Alice Wallenberg Foundation (KAW). The main site of the project is the Royal Institute of Technology
(KTH), School of Engineering Sciences in Chemistry, Biotechnology and Health (Stockholm, Sweden).
Additionally, the project involves research groups at Uppsala University, Karolinska Institutet, Chalmers
University of Technology and Lund University, as well as several present and past international
collaborations initiated with research groups in Europe, the United States, South Korea, China, and India.
Professor Mathias Uhlén is the director of the program.

The research underpinning the start of the exploration of the whole human proteome in the Human Protein
Atlas program was carried out in the late 1990s and early 2000s. A pilot study employing an affinity
proteomics strategy using affinity-purified antibodies raised against recombinant human protein fragments
was carried out for a chromosome-wide protein profiling of chromosome 21.[10] Other projects were also
carried out to establish processes for parallel and automated affinity purification of mono-specific antibodies
and their validation.[11][12]

Research
Antibodies and antigens, produced in the Human Protein Atlas workflow, are used in research projects to
study potential biomarkers in various diseases, such as breast cancer, prostate cancer, colon cancer, diabetes,
autoimmune diseases, ovarian cancer and renal failure.[13][14][15][16][17][18]

Researchers involved with Human Protein Atlas projects, are sharing protocols and method details in an
open-access group (https://www.protocols.io/groups/human-protein-atlas) on protocols.io.[19] A large effort
is put into validating the antibody reagents used for profiling of tissues and cells, and the HPA has
implemented stringent antibody validation criteria as suggested by the International Working Group for
Antibody Validation (IWGAV).[20][21][22]

Collaborations
The Human Protein Atlas program has participated in 9 EU research projects ENGAGE (http://www.eueng
age.org/index.html), PROSPECTS (http://www.prospects-fp7.eu), BIO_NMD (http://www.bio-nmd.eu),
AFFINOMICS (http://www.affinomics.org), CAGEKID (http://www.cng.fr/cagekid/), EURATRANS (htt
p://www.euratrans.eu), ITFoM (http://www.itfom.eu), DIRECT (http://www.direct-diabetes.org/index.php)
and PRIMES.

See also
Expression Atlas
The Cancer Genome Atlas

References
Text was copied from The Human Protein Atlas (https://www.proteinatlas.org/), which
is available under a Creative Commons Attribution-ShareAlike 3.0 Unported (https://creative
commons.org/licenses/by-sa/3.0/) license.
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