The broad, long-term objective of the proposed project is to enable mass spectrometry based protein research. The project will develop algorithms and software for peptide identification in difficult proteomics samples, including heavily modified samples, in which most peptides carry one or more modifications, and mutated samples, in which many peptides differ by one or more amino acid substitutions from the corresponding database peptides. One especially important type of heavily modified sample is a deliberately oxidized sample, used in the technique called """"""""oxidative footprinting"""""""" to obtain structural information for proteins and complexes. On difficult proteomics samples, the current peptide identification programs, such as Mascot and SEQUEST, generally give weak results, and there is very little means to assess the quality of the results. Thus the specific aims of the project are: (1) to develop statistical techniques to measure false discovery rates for modification and mutation identifications;(2) to build identification software for oxidative footprinting;and (3) to speed up and improve mutation and modification searching. If the project achieves its aims, biochemistry collaborators will use oxidative footprinting to study antibody-antigen binding for pathogenic bacteria, and will perform deeper and more thorough proteomic analyses of highly variable organisms such as Trypanosoma cruzi. More generally, proteomics laboratories worldwide, working on a wide variety of health related projects, will be able to analyze difficult samples. Researchers will be able to obtain structural information on proteins and complexes that are not amenable to x-ray crystallography or NMR;they will be able to study poorly sequenced and highly variable organisms;and they will be able to doublecheck proteomics analyses by searching for unanticipated chemical modifications. PUBIC
The importance of the proposed project to public health is that it will extend proteomics identifications to more difficult biological samples, such as samples containing unsequenced or poorly sequenced pathogens. The proposed work includes computational tools for """"""""oxidative footprinting"""""""", a powerful new technique for studying protein binding and conformations. This technique will enable the study of antibody-antigen binding for pathogenic bacteria;variation in antigens is currently one of the major obstacles to the development of vaccines.
| Brito, Alejandro E; Kletter, Doron; Singhal, Mudita et al. (2015) Benchmark study of automatic annotation of MALDI-TOF N-glycan profiles. J Proteomics 129:71-77 |
| Bern, Marshall; Brito, Alejandro E; Pang, Poh-Choo et al. (2013) Polylactosaminoglycan glycomics: enhancing the detection of high-molecular-weight N-glycans in matrix-assisted laser desorption ionization time-of-flight profiles by matched filtering. Mol Cell Proteomics 12:996-1004 |
| McClintock, Carlee S; Parks, Jerry M; Bern, Marshall et al. (2013) Comparative informatics analysis to evaluate site-specific protein oxidation in multidimensional LC-MS/MS data. J Proteome Res 12:3307-16 |
| Bern, Marshall; Kil, Yong J; Becker, Christopher (2012) Byonic: advanced peptide and protein identification software. Curr Protoc Bioinformatics Chapter 13:Unit13.20 |
| Bhatia, Swapnil; Kil, Yong J; Ueberheide, Beatrix et al. (2012) Constrained de novo sequencing of conotoxins. J Proteome Res 11:4191-200 |
| Becker, Christopher H; Bern, Marshall (2011) Recent developments in quantitative proteomics. Mutat Res 722:171-82 |
| Kil, Yong J; Becker, Christopher; Sandoval, Wendy et al. (2011) Preview: a program for surveying shotgun proteomics tandem mass spectrometry data. Anal Chem 83:5259-67 |
| Bern, Marshall; Saladino, Jessica; Sharp, Joshua S (2010) Conversion of methionine into homocysteic acid in heavily oxidized proteomics samples. Rapid Commun Mass Spectrom 24:768-72 |
| Chen, Xi; Drogaris, Paul; Bern, Marshall (2010) Identification of tandem mass spectra of mixtures of isomeric peptides. J Proteome Res 9:3270-9 |
| Bern, Marshall; Finney, Gregory; Hoopmann, Michael R et al. (2010) Deconvolution of mixture spectra from ion-trap data-independent-acquisition tandem mass spectrometry. Anal Chem 82:833-41 |
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