UC San Diego and Genentech scientists develop potentially disruptive antibody sequencing ...(f protein assembly is a puzzle rivaling ...)

The proposed Comparative Shotgun Protein Sequencing (CSPS) can be described as two-stage process: assembling mass spectra into long segments of a protein (SPS stage), and using similar proteins to order these segments into a complete protein sequence (comparative stage).

Bandeira offers a simple analogy for the algorithmic foundations of CSPS. "Imagine that the revised edition of a popular book has just been printed and that a competitor wishing to delay its release sneaks into the warehouse to shred all the books to pieces and destroys the original template," observed Bandeira, who recieved his Ph.D. in computer science and engineering from the UC San Diego Jacobs School of Engineering. "In this context, the SPS step allows one to reconstruct whole portions of the text by assembling snippets into sections and chapters (similar to a puzzle-solving approach), and the comparative step uses very old editions of the book to reorganize the parts back into a complete copy of the latest edition. By comparison with CSPS, competing protein-sequencing techniques are much more labor-intensive and would more closely resemble the process of asking the author to recite the whole book from memory."

Replacing Edman degradation with CSPS enables sequencing at a fraction of the time. In addition, CSPS automatically detects post-translational modifications that might never have been observed with Edman degradation or even other mainstream peptide-identification strategies.

"CSPS makes it possible to correlate unexpected modifications with changes in antibody efficiency, while simultaneously tracking mutations," said lead author Bandeira. "The process reveals unexpected changes that go undetected using traditional sequencing methods. This is critical for the biotech industry, because unexpected modifications may Concluded co-author Pavel Pevzner: "CSPS opens up many possibil
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