A Human Protein Atlas for Normal and Cancer Tissues Based on Antibody Proteomics

Department of Biotechnology, AlbaNova University Center, Royal Institute of Technology (KTH), SE-106 91 Stockholm, Sweden.
Molecular & Cellular Proteomics (Impact Factor: 6.56). 01/2006; 4(12):1920-32. DOI: 10.1074/mcp.M500279-MCP200
Source: PubMed


Antibody-based proteomics provides a powerful approach for the functional study of the human proteome involving the systematic generation of protein-specific affinity reagents. We used this strategy to construct a comprehensive, antibody-based protein atlas for expression and localization profiles in 48 normal human tissues and 20 different cancers. Here we report a new publicly available database containing, in the first version, approximately 400,000 high resolution images corresponding to more than 700 antibodies toward human proteins. Each image has been annotated by a certified pathologist to provide a knowledge base for functional studies and to allow queries about protein profiles in normal and disease tissues. Our results suggest it should be possible to extend this analysis to the majority of all human proteins thus providing a valuable tool for medical and biological research.

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    • "The inset shows the expression of the three galectin-9 splice variants. (B) Images of immunohistochemical staining of the galectins with detectable mRNA expression in NSCLC [27]. (C) Western blot analysis of galectin-9 isoform expression in NSCLC tumor tissue from 5 different patients. "
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    ABSTRACT: Approximately 30-40% of the patients with early stage non-small cell lung cancer (NSCLC) will present with recurrent disease within two years of resection. Here, we performed extensive galectin expression profiling in a retrospective study using frozen and paraffin embedded tumor tissues from 87 stage I/II NSCLC patients. Our data show that galectin mRNA expression in NSCLC is confined to galectin-1, -3, -4, -7, -8, and -9. Next to stage, univariable Cox regression analysis identified galectin-1, galectin-9FL and galectin-9Δ5 as possible prognostic markers. Kaplan-Meier survival estimates revealed that overall survival was significantly shorter in patients that express galectin-1 above median levels, i.e., 23.0 (2.9-43.1) vs. 59.9 (47.7-72.1) months (p = 0.020) as well as in patients that express galectin-9Δ5 or galectin-9FL below the median, resp. 59.9 (41.9-75.9) vs. 32.8 (8.7-56.9) months (p = 0.014) or 23.2 (-0.4-46.8) vs. 58.9 (42.9-74.9) months (p = 0.042). All three galectins were also prognostic for disease free survival. Multivariable Cox regression analysis showed that for OS, the most significant prognostic model included stage, age, gal-1 and gal-9Δ5 while the model for DFS included stage, age and gal-9Δ5. In conclusion, the current study confirms the prognostic value of galectin-1 and identifies galectin-9Δ5 as novel potential prognostic markers in early stage NSCLC. These findings could help to identify early stage NSCLC patients that might benefit most from adjuvant chemotherapy.
    Full-text · Article · Sep 2014 · PLoS ONE
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    • "We found that investigators involved in generating the IL32 antibody used Ensembl database as their source for the IL32 sequences instead of NCBI. The IL32 antibody supplied by Novus Biologicals has been used to examine an assortment of different tissues and diseases as part of the Human Protein Atlas project [22]. Related to their study, the Protein Atlas project provides (a) a list of the IL32 variant sequences that match the antigen sequence and (b) a direct link for convenient retrieval of the matching variant sequences, available through the Ensembl database. "
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    • "Peptide and protein identifications are mapped to a comprehensive reference protein database (for the latest human builds, the searched database is a combination of UniProtKB/Swiss-Prot, Ensembl, and sequences from the International Protein Index (IPI)), and postprocessed using the TPP [72]. It also annotates each protein and peptide with supporting data, such as genome mappings, sequence alignments, links to different databases, such as GPMDB or the Human Protein Atlas [73], uniqueness of peptide– protein mappings, observability of peptides, predicted observable peptides, estimated protein abundances and crossreferences to other databases, such as RefSeq, UniGene and UniProt. All the processed results are loaded into SBEAMS (systems biology experiment analysis management system) proteomics that is a proteomics analysis database built as a module under the SBEAMS framework. "
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