Propagating annotations of molecular networks using in silico fragmentation

Author(s)

da Silva, Ricardo R. ^{[1, 2]} ; Wang, Mingxun ^[1] ; Nothias, Louis-Felix ^[1] ; van der Hooft, Justin J. J. ^{[1, 3]} ; Caraballo-Rodriguez, Andres Mauricio ^[1] ; Fox, Evan ^[4] ; Balunas, Marcy J. ^[5] ; Klassen, Jonathan L. ^[4] ; Lopes, Norberto Peporine ^[2] ; Dorrestein, Pieter C. ^[1]

Affiliation

^[1] Univ Calif San Diego, Collaborat Mass Spectrometry Innovat Ctr, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 - USA

^[2] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Phys & Chem, NPPNS, Ribeirao Preto, SP - Brazil

^[3] Wageningen Univ, Dept Plant Sci, Bioinformat Grp, Wageningen - Netherlands

^[4] Univ Connecticut, Dept Mol & Cell Biol, Storrs, CT - USA

^[5] Univ Connecticut, Dept Pharmaceut Sci, Div Med Chem, Storrs, CT - USA

• Document type: Journal article
• Source: PLOS COMPUTATIONAL BIOLOGY; v. 14, n. 4 APR 2018.
• Web of Science Citations: 28

Abstract

The annotation of small molecules is one of the most challenging and important steps in untargeted mass spectrometry analysis, as most of our biological interpretations rely on structural annotations. Molecular networking has emerged as a structured way to organize and mine data from untargeted tandem mass spectrometry (MS/MS) experiments and has been widely applied to propagate annotations. However, propagation is done through manual inspection of MS/MS spectra connected in the spectral networks and is only possible when a reference library spectrum is available. One of the alternative approaches used to annotate an unknown fragmentation mass spectrum is through the use of in silico predictions. One of the challenges of in silico annotation is the uncertainty around the correct structure among the predicted candidate lists. Here we show how molecular networking can be used to improve the accuracy of in silico predictions through propagation of structural annotations, even when there is no match to a MS/MS spectrum in spectral libraries. This is accomplished through creating a network consensus of re-ranked structural candidates using the molecular network topology and structural similarity to improve in silico annotations. The Network Annotation Propagation (NAP) tool is accessible through the GNPS web-platform platform https://gnps.ucsd.edu/ProteoSAFe/static/gnps-theoretical.jp. (AU)

• FAPESP's process: 14/01884-2 - Analysis of metabolite profiles obtained by mass spectrometry using graphs
• Grantee: Ricardo Roberto da Silva
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 14/50265-3 - Distribution and metabolism of natural and synthetic xenobiotics: from the comprehension of reactional process to tissue imaging generation
• Grantee: Norberto Peporine Lopes
• Support Opportunities: BIOTA-FAPESP Program - Thematic Grants
• FAPESP's process: 15/03348-3 - Improvement of molecular networking using in silico fragmentation and subnetwork storage and search
• Grantee: Ricardo Roberto da Silva
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor