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MetaRiPPquest: A Peptidogenomics Approach for the Discovery of Ribosomally Synthesized and Post-translationally Modified Peptides

View ORCID ProfileHosein Mohimani, Alexey Gurevich, Kelsey L. Alexander, View ORCID ProfileC. Benjamin Naman, View ORCID ProfileTiago Leão, View ORCID ProfileEvgenia Glukhov, Nathan A. Moss, View ORCID ProfileTal Luzzatto-Knaan, Fernando Vargas, Louis-Felix Nothias, Nitin K. Singh, Jon G. Sanders, Rodolfo A. S. Benitez, Luke R. Thompson, Md-Nafiz Hamid, James T. Morton, Alla Mikheenko, Alexander Shlemov, Anton Korobeynikov, View ORCID ProfileIddo Friedberg, View ORCID ProfileRob Knight, Kasthuri Venkateswaran, William Gerwick, Lena Gerwick, Pieter C. Dorrestein, View ORCID ProfilePavel A. Pevzner
doi: https://doi.org/10.1101/227504
Hosein Mohimani
1Department of Computer Science and Engineering, University of California San Diego, La Jolla, California, USA,
2Computational Biology Department, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA,
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Alexey Gurevich
3Center for Algorithmic Biotechnology, Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia,
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Kelsey L. Alexander
4Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA,
5Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California, USA,
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C. Benjamin Naman
4Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA,
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Tiago Leão
4Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA,
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Evgenia Glukhov
4Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA,
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Nathan A. Moss
4Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA,
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Tal Luzzatto-Knaan
6Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA,
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Fernando Vargas
6Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA,
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Louis-Felix Nothias
6Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA,
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Nitin K. Singh
7Jet Propulsion Laboratory, California Institute of Technology, Pasadena, California, USA,
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Jon G. Sanders
8Department of Pediatrics, University of California San Diego, School of Medicine, La Jolla, California, USA,
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Rodolfo A. S. Benitez
8Department of Pediatrics, University of California San Diego, School of Medicine, La Jolla, California, USA,
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Luke R. Thompson
8Department of Pediatrics, University of California San Diego, School of Medicine, La Jolla, California, USA,
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Md-Nafiz Hamid
9Department of Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, Iowa, USA,
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James T. Morton
1Department of Computer Science and Engineering, University of California San Diego, La Jolla, California, USA,
8Department of Pediatrics, University of California San Diego, School of Medicine, La Jolla, California, USA,
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Alla Mikheenko
3Center for Algorithmic Biotechnology, Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia,
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Alexander Shlemov
3Center for Algorithmic Biotechnology, Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia,
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Anton Korobeynikov
3Center for Algorithmic Biotechnology, Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg, Russia,
10Department of Mathematics and Mechanics, St. Petersburg State University, St. Petersburg, Russia,
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Iddo Friedberg
9Department of Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, Iowa, USA,
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Rob Knight
1Department of Computer Science and Engineering, University of California San Diego, La Jolla, California, USA,
8Department of Pediatrics, University of California San Diego, School of Medicine, La Jolla, California, USA,
11Center for Microbiome Innovation, Jacobs School of Engineering, University of California, San Diego, La Jolla, California, USA.
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Kasthuri Venkateswaran
7Jet Propulsion Laboratory, California Institute of Technology, Pasadena, California, USA,
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William Gerwick
4Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA,
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Lena Gerwick
4Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA,
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Pieter C. Dorrestein
6Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA,
11Center for Microbiome Innovation, Jacobs School of Engineering, University of California, San Diego, La Jolla, California, USA.
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Pavel A. Pevzner
1Department of Computer Science and Engineering, University of California San Diego, La Jolla, California, USA,
10Department of Mathematics and Mechanics, St. Petersburg State University, St. Petersburg, Russia,
11Center for Microbiome Innovation, Jacobs School of Engineering, University of California, San Diego, La Jolla, California, USA.
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Abstract

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are an important class of natural products that include many antibiotics and a variety of other bioactive compounds. While recent breakthroughs in RiPP discovery raised the challenge of developing new algorithms for their analysis, peptidogenomic-based identification of RiPPs by combining genome/metagenome mining with analysis of tandem mass spectra remains an open problem. We present here MetaRiPPquest, a software tool for addressing this challenge that is compatible with large-scale screening platforms for natural product discovery. After searching millions of spectra in the Global Natural Products Social (GNPS) molecular networking infrastructure against just six genomic and metagenomic datasets, MetaRiPPquest identified 27 known and discovered 5 novel RiPP natural products.

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Posted December 03, 2017.
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MetaRiPPquest: A Peptidogenomics Approach for the Discovery of Ribosomally Synthesized and Post-translationally Modified Peptides
Hosein Mohimani, Alexey Gurevich, Kelsey L. Alexander, C. Benjamin Naman, Tiago Leão, Evgenia Glukhov, Nathan A. Moss, Tal Luzzatto-Knaan, Fernando Vargas, Louis-Felix Nothias, Nitin K. Singh, Jon G. Sanders, Rodolfo A. S. Benitez, Luke R. Thompson, Md-Nafiz Hamid, James T. Morton, Alla Mikheenko, Alexander Shlemov, Anton Korobeynikov, Iddo Friedberg, Rob Knight, Kasthuri Venkateswaran, William Gerwick, Lena Gerwick, Pieter C. Dorrestein, Pavel A. Pevzner
bioRxiv 227504; doi: https://doi.org/10.1101/227504
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MetaRiPPquest: A Peptidogenomics Approach for the Discovery of Ribosomally Synthesized and Post-translationally Modified Peptides
Hosein Mohimani, Alexey Gurevich, Kelsey L. Alexander, C. Benjamin Naman, Tiago Leão, Evgenia Glukhov, Nathan A. Moss, Tal Luzzatto-Knaan, Fernando Vargas, Louis-Felix Nothias, Nitin K. Singh, Jon G. Sanders, Rodolfo A. S. Benitez, Luke R. Thompson, Md-Nafiz Hamid, James T. Morton, Alla Mikheenko, Alexander Shlemov, Anton Korobeynikov, Iddo Friedberg, Rob Knight, Kasthuri Venkateswaran, William Gerwick, Lena Gerwick, Pieter C. Dorrestein, Pavel A. Pevzner
bioRxiv 227504; doi: https://doi.org/10.1101/227504

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