Human Protein Atlas

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 44 different normal human tissues and 20 different cancer types, as well as 46 different human cell lines.
Organisms Human
Contact
Research center KTH, UU, SciLifeLab, Sweden
Primary citation Towards a knowledge-based Human Protein Atlas[1]
Access
Website www.proteinatlas.org
Download URL www.proteinatlas.org/about/download
Tools
Web Advanced search, bulk retrieval/download
Miscellaneous
Versioning Yes
Data release
frequency
6 months
Version 15
Curation policy Yes – manual
Bookmarkable
entities
Yes – both individual protein entries and searches

The Human Protein Atlas (HPA) program is a scientific research program with the goal to explore the whole human proteome using an antibody-based approach. The program was started at the Royal Institute of Technology, Sweden, in 2003 and funded by the non-profit organization Knut and Alice Wallenberg Foundation (KAW).

The project has a gene-centric approach with the effort to map and characterize a representative protein for each protein-coding human gene (approximately 20,000 genes). Antibodies, both in-house produced and external (commercial and from collaborators), are validated in the HPA workflow and used for protein characterization. The data is released annually in a publicly available information database portal.[1]

The database includes protein expression profiles from 44 different normal and 20 different cancer tissues, 46 cell lines, subcellular localization and transcript expression levels. The database is searchable for a specific gene or protein. Functionalities added to the The Human Protein Atlas in later versions allow for combined searches, e.g. to find all proteins expressed in a certain organ or tissue or proteins differentially expressed in a specific tumor type.

History

The HPA 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 Biotechnology (Stockholm, Sweden). Professor Mathias Uhlén is the coordinator 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.[2] Other projects were also carried out to establish processes for parallel and automated affinity purification of mono-specific antibodies and their validation.,[3][4]

Research

Antibodies and antigens, produced in the HPA 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.[5][6][7][8][9][10]

In close collaboration to the HPA, a rodent brain atlas is also being built using the HPA-validated antibodies. Protein distribution is investigated in the nervous system of the rodent brain.[11]

Collaborations

The HPA program is participating in 9 EU research projects ENGAGE, PROSPECTS, BIO_NMD, AFFINOMICS, CAGEKID, EURATRANS, ITFoM, DIRECT and PRIMES.

References

  1. 1 2 Uhlen M, Oksvold P, Fagerberg L, Lundberg E, Jonasson K, Forsberg M, Zwahlen M, Kampf C, Wester K, Hober S, Wernerus H, Björling L, Ponten F (Dec 2010). "Towards a knowledge-based Human Protein Atlas". Nature Biotechnology 28 (12): 1248–50. doi:10.1038/nbt1210-1248. PMID 21139605.
  2. Agaton C, Galli J, Höidén Guthenberg I, Janzon L, Hansson M, Asplund A, Brundell E, Lindberg S, Ruthberg I, Wester K, Wurtz D, Höög C, Lundeberg J, Ståhl S, Pontén F, Uhlén M (Jun 2003). "Affinity proteomics for systematic protein profiling of chromosome 21 gene products in human tissues". Molecular & Cellular Proteomics 2 (6): 405–14. doi:10.1074/mcp.M300022-MCP200. PMID 12796447.
  3. Falk R, Agaton C, Kiesler E, Jin S, Wieslander L, Visa N, Hober S, Ståhl S (Dec 2003). "An improved dual-expression concept, generating high-quality antibodies for proteomics research". Biotechnology and Applied Biochemistry 38 (Pt 3): 231–9. doi:10.1042/BA20030091. PMID 12875650.
  4. Uhlén M, Björling E, Agaton C, Szigyarto CA, Amini B, Andersen E, et al. (Dec 2005). "A human protein atlas for normal and cancer tissues based on antibody proteomics". Molecular & Cellular Proteomics 4 (12): 1920–32. doi:10.1074/mcp.M500279-MCP200. PMID 16127175.
  5. Jonsson L, Gaber A, Ulmert D, Uhlén M, Bjartell A, Jirström K. "High RBM3 expression in prostate cancer independently predicts a reduced risk of biochemical recurrence and disease progression". Diagnostic Pathology 6: 91. doi:10.1186/1746-1596-6-91. PMID 21955582.
  6. Larsson A, Fridberg M, Gaber A, Nodin B, Levéen P, Jönsson G, Uhlén M, Birgisson H, Jirström K. "Validation of podocalyxin-like protein as a biomarker of poor prognosis in colorectal cancer". BMC Cancer 12: 282. doi:10.1186/1471-2407-12-282. PMID 22769594.
  7. Lindskog C, Asplund A, Engkvist M, Uhlen M, Korsgren O, Ponten F (Jun 2010). "Antibody-based proteomics for discovery and exploration of proteins expressed in pancreatic islets". Discovery Medicine 9 (49): 565–78. PMID 20587347.
  8. Neiman M, Hedberg JJ, Dönnes PR, Schuppe-Koistinen I, Hanschke S, Schindler R, Uhlén M, Schwenk JM, Nilsson P (Nov 2011). "Plasma profiling reveals human fibulin-1 as candidate marker for renal impairment". Journal of Proteome Research 10 (11): 4925–34. doi:10.1021/pr200286c. PMID 21888404.
  9. Nodin B, Fridberg M, Jonsson L, Bergman J, Uhlén M, Jirström K. "High MCM3 expression is an independent biomarker of poor prognosis and correlates with reduced RBM3 expression in a prospective cohort of malignant melanoma". Diagnostic Pathology 7: 82. doi:10.1186/1746-1596-7-82. PMID 22805320.
  10. Schwenk JM, Igel U, Neiman M, Langen H, Becker C, Bjartell A, Ponten F, Wiklund F, Grönberg H, Nilsson P, Uhlen M (Nov 2010). "Toward next generation plasma profiling via heat-induced epitope retrieval and array-based assays". Molecular & Cellular Proteomics 9 (11): 2497–507. doi:10.1074/mcp.M110.001560. PMID 20682762.
  11. Mulder J, Spence L, Tortoriello G, Dinieri JA, Uhlén M, Shui B, Kotlikoff MI, Yanagawa Y, Aujard F, Hökfelt T, Hurd YL, Harkany T (Jun 2010). "Secretagogin is a Ca2+-binding protein identifying prospective extended amygdala neurons in the developing mammalian telencephalon". The European Journal of Neuroscience 31 (12): 2166–77. doi:10.1111/j.1460-9568.2010.07275.x. PMID 20529129.
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