Onco-proteogenomics: a novel approach to identify cancer-specific mutations combining proteomics and transcriptome deep sequencing
© Helmy et al; licensee BioMed Central Ltd. 2010
Published: 11 October 2010
The accumulation of somatic mutation is a common property in all cancer genomes. These mutations include several patterns of mutagenesis such as small insertions, chromosomal rearrangement and nucleotide substitutions. Consequently, the mutated genomes produce mutant transcriptome and, therefore, mutant proteins that give the cancer cell its oncogenic properties . For such mutated proteins, however, mass spectrometry-based identification by shotgun proteomics is generally difficult because the identification is dependent on databases containing normal proteins or hybrid database with normal and mutated proteins. Here, we present 'onco-proteogenomics, a novel proteogenomics approach to identify the cancer-related peptides (phospho- and non-phospho peptides) and proteins.
We analyzed 15 MS/MS runs of HeLa S3 cells, as a test sample, by shotgun proteomics and phosphoproteomics. The obtained data was analyzed by an extended version of MSSS (MS Spectra Sequential Subtraction), the proteogenomic approach that we used before in the identification of novel genomic features in Rice plant . In our onco- proteogenomic approach, we used four databases containing normal sequences (Human protein, cDNA, mRNA and genome databases) for Mascot peptide identification and removed all the MS/MS spectra that corresponds to all identified peptides. The reminder MS/MS spectra were searched against one cancer-driven database obtained through deep sequencing of HeLa S3 cells to identify cancer-specific peptides.
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