The Smith Group is an interdisciplinary group of researchers engaged in executing important, interesting, and impactful science with fun people. We seek to develop powerful new technologies that enable and drive biological research. Most of our present work revolves around mass spectrometry in one form or another. Current areas of focus include developing improved technology for the comprehensive identification and quantification of proteoforms in complex systems, elucidating the roles of dehydroamino acids in HIV biology and Alzheimer’s disease, and new mass spectrometry strategies for epitranscriptomics. We apply these tools and drive their development in important biological systems with the aid of talented biologist and clinician collaborators.
Publications and Collaborations
For an up-to-date list of publications, please see Lloyd’s Google Scholar Page
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Collaborations
| Robert Bremel | ioGenetics |
| Emery Bresnick | University of Wisconsin-Madison, Cell & Regenerative Biology |
| Wilfred van der Donk | University of Illinois Urbana-Champaign, Chemistry |
| David Jarrard | University of Wisconsin-Madison, Urology |
| Ryan Julian | University of California, Riverside, Chemistry |
| Uri Keich | University of Sydney, School of Mathematics and Statistics |
| Neil Kelleher | Northwestern University, Chemistry |
| Jeffrey Martell | University of Wisconsin-Madison, Chemistry |
| Michael Marty | University of Arizona, Chemistry and Biochemistry |
| David Morgenstern | The Nancy and Stephen Grand Israel National Center for Personalized Medicine |
| William S. Noble | University of Washington, Genome Sciences, Computer Science & Engineering |
| Samuel Payne | Brigham Young University, Biology |
| Nathan Sherer | University of Wisconsin-Madison, Molecular Virology and Oncology |
| Randall Tibbetts | University of Wisconsin-Madison, Oncology |
| Nathan Welham | University of Wisconsin- Madison, Surgery |
| Ren Xi | Carnegie Mellon University, Biomedical Engineering |
Software Development & Expertise
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MetaMorpheus
MetaMorpheus is a software tool that identifies peptides, proteins, and proteoforms from mass spectrometry fragmentation (MS/MS) data. It is capable of searching both bottom-up (peptide) and top-down (intact proteoform) data. Currently, five graduate students and several undergraduates work on improving MetaMorpheus, making it one of our most collaborative and dynamic projects. Often, the motivation for adding a feature to MetaMorpheus is the need to analyze new types of data that existing software simply cannot handle. We use computer programming as a tool to solve these problems, much like traditional chemical biology uses organic chemistry to probe biological systems. MetaMorpheus was specifically designed to identify the “dark matter” of proteomics; where most search programs attempt to identify mostly unmodified peptides, we provide the capability of identifying peptides with a wide range of post-translational modifications. Recently, we have added the ability to identify proteoforms, chemically crosslinked peptides, and isotopically-labeled peptides. We also focus on providing this tool to the proteomics community as a free, open-source, easy-to-use tool. We have a community of over 200 users, which grows every day. We are constantly adding new features to the software, and release new versions of MetaMorpheus every few weeks.
FlashLFQ
FlashLFQ is a program that quantifies peptides, proteins, and proteoforms in mass spectrometry data. This step is performed after these analytes have been identified by a search program, such as MetaMorpheus. As the name implies, it is orders of magnitude faster than existing quantification software. The primary goal of the software is to provide a fast, high-quality, quantitative platform to quantify any search software’s identifications.
Proteoform Suite
Proteoform Suite is a software program that performs intact-mass analysis and quantification of proteoforms in mass spectrometry MS1-only data. In a typical top-down analysis, more proteoforms are observed in the MS1 spectra than identified by MS2; Proteoform Suite increases the number of proteoform identifications in top-down analyses by identifying proteoforms by accurate intact mass. Proteoform Suite also constructs and automates the visualization of proteoform families by grouping together related proteoforms based on mass differences and liquid chromatography elution time. Proteoform Suite can integrate both bottom-up and top-down data to maximize the number of proteoform identifications.
mzLib
mzLib is a library for mass spectrometry projects.
ProteaseGuru
ProteaseGuru is a in silico digestion tool for the planning of bottom-up proteomic experiments. ProteaseGuru allows for the digestion of one or more protein databases with as many proteases as desired. Results of the various proteolytic digests can be visualized with histograms as well as protein sequence coverage maps.