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Sci Rep. 2016 May 11;6:25619. doi: 10.1038/srep25619.

Integrative analysis of extracellular and intracellular bladder cancer cell line proteome with transcriptome: improving coverage and validity of -omics findings.

Author information

1
Biotechnology Division, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
2
Charité-Universitätsmedizin Berlin, Berlin, Germany.
3
Mosaiques Diagnostics GmbH, Hannover, Germany.
4
GenomeScan B.V., Leiden, The Netherlands.
5
Institut National de la Santé et de la Recherche Médicale (INSERM), Institut of Cardiovascular and Metabolic Disease, Toulouse, France.
6
Université Toulouse III Paul-Sabatier, Toulouse, France.
7
BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
8
Department of Urology, University of Lübeck, Lübeck, Germany.
9
Department of Urology and Urological Oncology, Hannover Medical School, Hannover, Germany.
10
RWTH-Aachen, Institute for Molecular Cardiovascular Research (IMCAR), Aachen, Germany.

Abstract

Characterization of disease-associated proteins improves our understanding of disease pathophysiology. Obtaining a comprehensive coverage of the proteome is challenging, mainly due to limited statistical power and an inability to verify hundreds of putative biomarkers. In an effort to address these issues, we investigated the value of parallel analysis of compartment-specific proteomes with an assessment of findings by cross-strategy and cross-omics (proteomics-transcriptomics) agreement. The validity of the individual datasets and of a "verified" dataset based on cross-strategy/omics agreement was defined following their comparison with published literature. The proteomic analysis of the cell extract, Endoplasmic Reticulum/Golgi apparatus and conditioned medium of T24 vs. its metastatic subclone T24M bladder cancer cells allowed the identification of 253, 217 and 256 significant changes, respectively. Integration of these findings with transcriptomics resulted in 253 "verified" proteins based on the agreement of at least 2 strategies. This approach revealed findings of higher validity, as supported by a higher level of agreement in the literature data than those of individual datasets. As an example, the coverage and shortlisting of targets in the IL-8 signalling pathway are discussed. Collectively, an integrative analysis appears a safer way to evaluate -omics datasets and ultimately generate models from valid observations.

PMID:
27167498
PMCID:
PMC4863247
DOI:
10.1038/srep25619
[Indexed for MEDLINE]
Free PMC Article

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