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A genecentric human protein atlas for expression profiles based on antibodies
KTH, School of Biotechnology (BIO), Proteomics.
KTH, School of Biotechnology (BIO), Proteomics.
KTH, School of Biotechnology (BIO), Proteomics.ORCID iD: 0000-0003-3014-5502
KTH, School of Biotechnology (BIO), Proteomics.ORCID iD: 0000-0003-0198-7137
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2008 (English)In: Molecular & Cellular Proteomics, ISSN 1535-9476, Vol. 7, no 10, 2019-2027 p.Article in journal (Refereed) Published
Abstract [en]

An attractive path forward in proteomics is to experimentally annotate the human protein complement of the genome in a genecentric manner. Using antibodies, it might be possible to design protein-specific probes for a representative protein from every protein-coding gene and to subsequently use the antibodies for systematical analysis of cellular distribution and subcellular localization of proteins in normal and disease tissues. A new version (4.0) of the Human Protein Atlas has been developed in a genecentric manner with the inclusion of all human genes and splice variants predicted from genome efforts together with a visualization of each protein with characteristics such as predicted membrane regions, signal peptide, and protein domains and new plots showing the uniqueness (sequence similarity) of every fraction of each protein toward all other human proteins. The new version is based on tissue profiles generated from 6120 antibodies with more than five million immunohistochemistry-based images covering 5067 human genes, corresponding to similar to 25% of the human genome. Version 4.0 includes a putative list of members in various protein classes, both functional classes, such as kinases, transcription factors, G-protein-coupled receptors, etc., and project-related classes, such as candidate genes for cancer or cardiovascular diseases. The exact antigen sequence for the internally generated antibodies has also been released together with a visualization of the application-specific validation performed for each antibody, including a protein array assay, Western blot analysis, immunohistochemistry, and, for a large fraction, immunofluorescence-based confocal microscopy. New search functionalities have been added to allow complex queries regarding protein expression profiles, protein classes, and chromosome location. The new version of the protein atlas thus is a resource for many areas of biomedical research, including protein science and biomarker discovery.

Place, publisher, year, edition, pages
2008. Vol. 7, no 10, 2019-2027 p.
Keyword [en]
CANCER TISSUES; PROTEOMICS; RESOURCE; DATABASE; MICROARRAYS; GENERATION; LIBRARIES; PEPTIDES; GENOME
National Category
Industrial Biotechnology
Identifiers
URN: urn:nbn:se:kth:diva-9745DOI: 10.1074/mcp.R800013-MCP200ISI: 000260424700018OAI: oai:DiVA.org:kth-9745DiVA: diva2:127400
Note
QC 20100708Available from: 2008-12-05 Created: 2008-12-05 Last updated: 2010-07-08Bibliographically approved
In thesis
1. Databases for antibody-based proteomics
Open this publication in new window or tab >>Databases for antibody-based proteomics
2008 (English)Doctoral thesis, comprehensive summary (Other scientific)
Abstract [en]

Humans are believed to have ~20,500 protein-coding genes andmuch effort has over the last years been put into the characterizationand localization of the encoded proteins in order to understand theirfunctions. One such effort is the Human Proteome Resource (HPR)project, started in Sweden 2003 with the aim to generate specificantibodies to each human protein and to use those antibodies toanalyze the human proteome by screening human tissues and cells.The work reported in this thesis deals with structuring of data fromantibody-based proteomics assays, with focus on the importance ofaggregating and presenting data in a way that is easy to apprehend.The goals were to model and build databases for collecting, searchingand analyzing data coming out of the large-scale HPR project and tomake all collected data publicly available. A public website, theHuman Protein Atlas, was developed giving all end-users in thescientific community access to the HPR database with proteinexpression data. In 2008, the Human Protein Atlas was released in its4th version containing more than 6000 antibodies, covering more than25% of the human proteins. All the collected protein expression datais searchable on the public website. End-users can query for proteinsthat show high expression in one tissue and no expression in anotherand possibly find tissue specific biomarkers. Queries can also beconstructed to find proteins with different expression levels in normalvs. cancer tissues. The proteins found by such a query could identifypotential biomarkers for cancer that could be used as diagnosticmarkers and maybe even be involved in cancer therapy in the future.Validation of antibodies is important in order to get reliable resultsfrom different assays. It has been noted that some antibodies arereliable in certain assays but not in others and therefore anotherpublicly available database, the Antibodypedia, has been createdwhere any antibody producer can submit their binders together withthe validation data in order for end users to purchase the bestantibody for their protein target and their intended assay.

Place, publisher, year, edition, pages
Stockholm: KTH, 2008. 68 p.
Series
Trita-BIO-Report, ISSN 1654-2312 ; 2008:24
Keyword
proteomics, antibodies, database, biomarker, website
National Category
Industrial Biotechnology
Identifiers
urn:nbn:se:kth:diva-9658 (URN)978-91-7415-161-9 (ISBN)
Public defence
2008-12-19, FD5, AlbaNova, Roslagstullsbacken 21, Stockholm, 10:00 (English)
Opponent
Supervisors
Note
QC 20100708Available from: 2008-12-05 Created: 2008-11-24 Last updated: 2010-07-08Bibliographically approved

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Oksvold, PerFagerberg, LinnAl-Khalili Szigyarto, CristinaLundberg, EmmaHober, SophiaUhlén, Mathias

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Berglund, LisaBjörling, ErikOksvold, PerFagerberg, LinnAl-Khalili Szigyarto, CristinaPersson, AnjaOttosson, JennyWernérus, HenrikNilsson, PeterLundberg, EmmaSivertsson, ÅsaHober, SophiaUhlén, Mathias
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