|
|
| Overlapping MS/MS Spectra and Disease Proteomics |
| Wed 2:30 PM - Session: New Advances |
| Nuno Bandeira |
| The ongoing success of the proteomics endeavor is the result of a prolific symbiosis between experimental ingenuity and efficient bioinformatics. But despite valuable contributions, the road to a better understanding of disease proteomics is still hurdled by significant difficulties in the extensive identification of post-translational modifications and in the sequencing of novel proteins like antibodies or cancer fusion proteins.
Recently, tandem mass spectrometry (MS/MS) based approaches seemed to be reaching the limit on the amount of information that could be extracted from MS/MS spectra. However, a closer look reveals that a common limiting procedure is to analyze each spectrum in isolation, even though high throughput mass spectrometry regularly generates many spectra from related peptides. By capitalizing on this redundancy we have shown that, similarly to the alignment of protein sequences, unidentified MS/MS spectra can also be aligned for the identification of multiple modified variants of the same peptide. The highly correlated peaks in spectra from variants of the same peptide reliably identify all known and even some unknown modifications in a sample of cataractous lenses proteins. Furthermore, the combination of shotgun proteomics with the alignment of spectra from overlapping peptides led us to the development of Shotgun Protein Sequencing |