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Originally published In Press as doi:10.1074/mcp.M700411-MCP200 on October 3, 2007.
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Molecular & Cellular Proteomics 7:825-844, 2008.
© 2008 by The American Society for Biochemistry and Molecular Biology, Inc.

Research

A Web-based Tool for in Silico Biomarker Discovery Based on Tissue-specific Protein Profiles in Normal and Cancer Tissues*,S

Erik Björling{ddagger}, Cecilia Lindskog§, Per Oksvold{ddagger}, Jerker Linné§, Caroline Kampf§, Sophia Hober{ddagger}, Mathias Uhlén{ddagger} and Fredrik Pontén§,¶

From the {ddagger} School of Biotechnology, AlbaNova University Center, Royal Institute of Technology (KTH), SE-106 91 Stockholm, Sweden and § Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden

Here we report the dev elopment 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.

To whom correspondence should be addressed. Tel.: 46-18-611-38-46; Fax: 46-18-55-33-54; E-mail: fredrik.ponten{at}genpat.uu.se






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