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A web-based tool for in silico biomarker discovery based on tissue-specific protein profiles in normal and cancer tissues
KTH, School of Biotechnology (BIO), Proteomics.
Uppsala Univ, Rudbeck Lab.
KTH, School of Biotechnology (BIO), Proteomics.ORCID iD: 0000-0003-3014-5502
Uppsala Univ, Rudbeck Lab.
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2008 (English)In: Molecular & Cellular Proteomics, ISSN 1535-9476, Vol. 7, no 5, 825-844 p.Article in journal (Refereed) Published
Abstract [en]

Here we report the development of a publicly available Web-based analysis tool for exploring proteins expressed in a tissue- or cancer-specific manner. The search queries are based on the human tissue profiles in normal and cancer cells in the Human Protein Atlas portal and rely on the individual annotation performed by pathologists of images representing immunohistochemically stained tissue sections. Approximately 1.8 million images representing more than 3000 antibodies directed toward human proteins were used in the study. The search tool allows for the systematic exploration of the protein atlas to discover potential protein biomarkers. Such biomarkers include tissue-specific markers, cell type-specific markers, tumor type-specific markers, markers of malignancy, and prognostic or predictive markers of cancers. Here we show examples of database queries to generate sets of candidate biomarker proteins for several of these different categories. Expression profiles of candidate proteins can then subsequently be validated by examination of the underlying high resolution images. The present study shows examples of search strategies revealing several potential protein biomarkers, including proteins specifically expressed in normal cells and in cancer cells from specified tumor types. The lists of candidate proteins can be used as a starting point for further validation in larger patient cohorts using both immunological approaches and technologies utilizing more classical proteomics tools.

Place, publisher, year, edition, pages
2008. Vol. 7, no 5, 825-844 p.
Keyword [en]
ANTIBODY-BASED PROTEOMICS; HUMAN BREAST-CANCER; PROSTATE-CANCER; GENE-EXPRESSION; IMMUNOHISTOCHEMICAL MARKERS; CELL MICROARRAYS; METASTASIS; RESOURCE; ANTIGEN; GROWTH
National Category
Industrial Biotechnology
Identifiers
URN: urn:nbn:se:kth:diva-9744DOI: 10.1074/mcp.M700411-MCP200ISI: 000255830200001Scopus ID: 2-s2.0-43849094501OAI: oai:DiVA.org:kth-9744DiVA: diva2:127399
Note
QC 20100708Available from: 2008-12-05 Created: 2008-12-05 Last updated: 2011-09-02Bibliographically 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, PerHober, SophiaUhlén, Mathias

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