Human Protein Atlas

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Human Protein Atlas
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The Human Protein Atlas is a publicly accessible database with millions of high-resolution images showing the spatial distribution of proteins in tissues, tumors and cells.
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On-line 2005
https://www.proteinatlas.org/

The Human Protein Atlas (HPA) is a Swedish research project that started in 2003 with the aim of mapping all human proteins in cells , tissues and organs by integrating various omics technologies. These include antibody- based imaging, mass spectrometry- based proteomics , transcriptomics and systems biology approaches. All information in the database is freely accessible. Since version 19, the HPA has consisted of six separate parts, each focusing on a specific aspect of the genome-wide analysis of the human proteomefocus: the tissue atlas shows the distribution of proteins in tissues and organs; the cell atlas shows the subcellular localization to organelles and comparable structures in individual cells; the pathology atlas shows the effects of protein expression on the survival of patients with cancer; the brain atlas shows the protein expression in the different brain regions; the blood atlas focuses on gene expression in blood cells; and finally the Metabolism Atlas, which describes the metabolic pathways in human tissue. The HPA project has already contributed to more than a thousand publications in the field of human biology and was selected on July 25, 2017 by the organization ELIXIR for its fundamental importance as a European core resource. The HPA consortium is funded by the Knut and Alice Wallenberg Foundation.

Components of the Human Protein Atlas

The Human Protein Atlas consists of 6 sub-atlases:

  • The tissue atlas contains information on the expression profiles of human genes at both the mRNA and protein level. Protein expression data are derived from antibody-based protein profiles using immunohistochemistry . A total of 76 different cell types were analyzed, which correspond to 44 healthy human tissue types. The data are presented as pathology-based annotation of protein expression levels. All underlying images of immunohistochemically stained normal tissues are accessible as high-resolution images in the tissue atlas.
  • The cell atlas offers high-resolution insights into the spatial distribution of proteins in cells. For this purpose, cell culture cells are stained with antibody-based methods and then images are taken with confocal microscopy . The cell atlas is based on 64 cell lines that represent the various organs and tissues of the human body. The mRNA expression of all human genes from these cell lines was characterized by deep RNA sequencing. The subcellular distribution of proteins is examined in a subgroup of cell lines and classified into 32 different organelles and fine cell structures.
  • The Pathology Atlas is based on the analysis of 17 main cancer types with data from 8,000 patients. It also introduces a new concept for presenting patient survival data called the Interactive Survival Scatter Plot, and the atlas includes more than 400,000 such plots. A national supercomputing center was used to analyze more than 2.5 petabytes of publicly available data from the Cancer Genome Atlas (TCGA) to generate more than 900,000 survival charts showing the effects of RNA and protein levels on clinical survival describe. The Pathology Atlas also contains 5 million pathological images created by the Human Protein Atlas Consortium.
  • The Brain Atlas examines protein expression in the mammalian brain by visualizing and integrating data from three mammalian species (human, pig, and mouse). For this purpose, transcriptomics data and antibody-based staining are used to examine the proteome in detail of a single cell.
  • The blood atlas contains RNA expression profiles for various leukocytes (B and T cells, monocytes, granulocytes and dendritic cells). A total of 18 cell types are covered, which were isolated by cell sorting and subsequent RNA sequence analysis.
  • Together with the tissue atlas, the metabolism atlas enables research into protein function and tissue-specific gene expression in the context of the human metabolic network.

history

The Human Protein Atlas program started in 2003 and has been funded from the start by the non-profit Knut and Alice Wallenberg Foundation (KAW). The main location of the project is the Royal Technical University (KTH) in Stockholm. The foundations for the program were laid in the late 1990s and early 00s. A pilot study investigated the success of an affinity proteomics strategy in which antibodies against recombinant human protein fragments were used to carry out a chromosome-wide protein characterization of chromosome 21.

research

The antibodies and antigens that have emerged as part of the HPA program are used in a large number of research projects. Their usefulness in terms of possible biomarkers for various cancers is examined.

collaboration

The HPA program takes part in the following nine EU research projects: ENGAGE , PROSPCTS , BIO_NMD , AFFINOMICS , CAGEKID , EURATRANS , ITFoM , DIRECT and PRIME .

Individual evidence

  1. ↑ Mathias Uhlen, Linn Fagerberg, Bjorn M. Hallstrom, Cecilia Lindskog Per Oksvold: Tissue-based map of the human proteome . In: Science . tape 347 , no. 6220 , January 23, 2015, ISSN  0036-8075 , p. 1260419 , doi : 10.1126 / science.1260419 , PMID 25613900 ( sciencemag.org [accessed July 17, 2018]).
  2. ↑ Peter J. Thul, Lovisa Åkesson, Mikaela Wiking, Diana Mahdessian, Aikaterini Geladaki: A subcellular map of the human proteome . In: Science . tape 356 , no. 6340 , May 26, 2017, ISSN  0036-8075 , p. eaal3321 , doi : 10.1126 / science.aal3321 , PMID 28495876 ( sciencemag.org [accessed July 17, 2018]).
  3. ^ Mathias Uhlen, Cheng Zhang, Sunjae Lee, Evelina Sjöstedt, Linn Fagerberg: A pathology atlas of the human cancer transcriptome . In: Science . tape 357 , no. 6352 , August 18, 2017, ISSN  0036-8075 , p. eaan2507 , doi : 10.1126 / science.aan2507 , PMID 28818916 ( sciencemag.org [accessed July 17, 2018]).
  4. ^ Charlotta Agaton, Joakim Galli, Ingmarie Höidén-Guthenberg, Lars Janzon, Marianne Hansson: Affinity Proteomics for Systematic Protein Profiling of Chromosome 21 Gene Products in Human Tissues . In: Molecular & Cellular Proteomics . tape 2 , no. 6 , June 1, 2003, ISSN  1535-9476 , p. 405-414 , doi : 10.1074 / mcp.M300022-MCP200 , PMID 12796447 ( mcponline.org [accessed July 17, 2018]).
  5. ↑ Liv Jonsson, Alexander Gaber, David Ulmert, Mathias Uhlén, Anders Bjartell: High RBM3 expression in prostate cancer independently predicts a reduced risk of biochemical recurrence and disease progression . In: Diagnostic Pathology . tape 6 , no. 1 , 2011, ISSN  1746-1596 , pp. 91 , doi : 10.1186 / 1746-1596-6-91 , PMID 21955582 .
  6. ↑ Anna Larsson, Marie Fridberg, Alexander Gaber, Björn Nodin, Per Levéen: Validation of podocalyxin-like protein as a biomarker of poor prognosis in colorectal cancer . In: BMC Cancer . tape 12 , no. 1 , July 8, 2012, ISSN  1471-2407 , doi : 10.1186 / 1471-2407-12-282 , PMID 22769594 .
  7. ↑ Björn Nodin, Marie Fridberg, Liv Jonsson, Julia Bergman, Mathias Uhlén: High MCM3 expression is an independent biomarker of poor prognosis and correlates with reduced RBM3 expression in a prospective cohort of malignant melanoma . In: Diagnostic Pathology . tape 7 , no. 1 , 2012, ISSN  1746-1596 , p. 82 , doi : 10.1186 / 1746-1596-7-82 , PMID 22805320 .