Top-Down Proteomics

The emerging applications of top-down MS and fast progress in top-down instrumentation call for development of new software for top-down proteomics. CCMS developed MS-Deconv deconvolution software as well as MS-Align+ tool for protein identification that computes rigorous E-values of Protein-Spectrum Matches. CCMS is now developing algorithms and software to support emerging applications of top-down MS including identification of ultramodified proteins such as histones.

Top-Down Proteomics

Software Tools & Datasets

MS-Deconv: Tool home page
MS-Align+: Tool home page

Key Publications

Identification of ultramodified proteins using top-down tandem mass spectra. Liu X, Hengel S, Wu S, Tolić N, Pasa-Tolić L, Pevzner PA. J Proteome Res. 2013 Dec 6;12(12):5830-8. doi: 10.1021/pr400849y. Epub 2013 Nov 15.
Deconvolution and database search of complex tandem mass spectra of intact proteins: a combinatorial approach. Liu X, Inbar Y, Dorrestein PC, Wynne C, Edwards N, Souda P, Whitelegge JP, Bafna V, Pevzner PA. Mol Cell Proteomics. 2010 Dec;9(12):2772-82. doi: 10.1074/mcp.M110.002766. Epub 2010 Sep 20.
Protein identification using top-down. Liu X, Sirotkin Y, Shen Y, Anderson G, Tsai YS, Ting YS, Goodlett DR, Smith RD, Bafna V, Pevzner PA. Mol Cell Proteomics. 2012 Jun;11(6):M111.008524. doi: 10.1074/mcp.M111.008524. Epub 2011 Oct 25.
Speeding up tandem mass spectral identification using indexes. Liu X, Mammana A, Bafna V. Bioinformatics. 2012 Jul 1;28(13):1692-7. doi: 10.1093/bioinformatics/bts244. Epub 2012 Apr 27.
Interpreting top-down mass spectra using spectral alignment Frank AM, Pesavento JJ, Mizzen CA, Kelleher NL, Pevzner PA. Anal Chem. 2008 Apr 1;80(7):2499-505. doi: 10.1021/ac702324u. Epub 2008 Feb 27.
Top-down proteomics reveals a unique protein s-thiolation switch in the bacterial pathogen salmonella in response to infection-like conditions C. Ansong, S. Wu, M. Da, X. Liu, H. Brewer, L. Brooke, D. Kaiser, Nakayasu E.S., P.A. Cort, J.R.and Pevzner, R.D. Smith, F. Heffron, J.N. Adkins, and L. Pasa-Tolic. Proc Natl Acad Sci U S A, 110:10153--8, 2013.
View All CCMS Publictions

While MS-Align+ proved to be fast and accurate tool, many important challenges in top-down MS remain unaddressed. CCMS is developing algorithms and software to support emerging applications of top-down MS. In collaboration with leading top-down groups, these algorithms will be used to catalog the histone PTM space, derive rules governing the combinatorial histone code, and to develop new inexpensive and robust technology for antibody sequencing.