MASST: A Web-based Basic Mass Spectrometry Search Tool for Molecules to Search Public Data

Abstract

Correspondence:We introduce a web-enabled small-molecule mass spectrometry (MS) search engine. To date, no tool can query all the public small-molecule tandem MS data in metabolomics repositories, greatly limiting the utility of these resources in clinical, environmental and natural product applications. Therefore, we introduce a Mass Spectrometry Search Tool (MASST) (https://proteosafe-extensions.ucsd.edu/masst/), that enables the discovery of molecular relationships among accessible public metabolomics and natural product tandem mass spectrometry data (MS/MS).The ability to discover related sequences of proteins or genes in publicly accessible sequence data using Basic Local Alignment Search Tool (BLAST), connected to public sequence data repositories through a web interface (WebBLAST, https://blast.ncbi.nlm.nih.gov/Blast.cgi), was introduced in the 1990s. 1 It has garnered more than 138,159 citations according to Google Scholar, placing it among the most widely used bioinformatics tools. WebBLAST enabled detection of the number of sequences in public repositories related to a given query, the organisms in which those sequences occur, and the evolutionary and inferred functional relationships among related sequences. It therefore permitted a broad community to answer simple but scientifically compelling questions such as: Is a protein or DNA sequence common or rare? How is this sequence distributed among different kinds of organisms? What other sequences are related to this sequence (evolutionary variants, or new mutations, or synthetic constructs)? In the early days of making DNA or protein sequence data publicly available, the "metadata" (e.g., contextual information about the sample, population and location the sequence came from, and technical information about how it was produced) in the public repositories was limited and no standards existed. This is a situation similar to the current status of much of the mass spectrometry data in the public domain. However, when publicly deposited data has metadata available, such as organism, location of sampling, host phenotypes such as diseases, etc., it becomes possible to start building higherlevel hypotheses regarding the evolutionary, ecological or functional relationships among these DNA, RNA or protein sequences. The development of the ability to search data with added context continues to have profound impacts on fields including medicine, chemistry, genetics, molecular biology, genomics, microbiology, and ecology.Algorithms developed for mass spectrometry data, including molecular networking 2 and fragmentation trees 3 , enable similarity searches, while powerful metabolomics analysis software infrastructures, such as MS-DIAL 4 , MetaboAnalyst 5 , XCMS Online 6 , HMDB 7 , some of which have been available for over a decade, focus on annotation of MS/MS spectra or finding statistical relationships between molecular features. However, none of the existing tools enable searching against public data in repositories. Finding the distribution of specific data of i...

Feature-based Molecular Networking in the GNPS Analysis Environment

“…The benefit of using FBMN can be illustrated with the metal chelating agent ethylenediaminetetraacetic acid (EDTA), widely used in beauty products, food, and scientific protocols. A search for its occurrences in public spectral datasets with the mass spectrometry search tool (MASST) 24 showed that it is frequently observed in plasma samples where it is used during the sample preparation. We took one of the public human serum sample datasets ( MSV00008263 ) where EDTA was observed.…”

Protocol for Community-created Public MS/MS Reference Library Within the GNPS Infrastructure

“…We demonstrated the ability to readily determine the location in which the chemical standards MS/MS spectrum selected via MSMS-Chooser were found using MASST. 11 Any additional MS/MS spectra uploaded to the GNPS MS/MS spectral library will be included in the periodic living data analysis in GNPS. Data submitters will be emailed when new chemical annotations are found in their MassIVE deposited data.…”

“…Upon completion of the job, the resulting file output of MSMS-Chooser should be checked manually for accuracy, and poor quality or incorrect spectra should be deleted (row-wise) from the results table. The MSMS-Chooser output was then used to generate the associated MS/MS library spectra which were subsequently uploaded to the GNPS MS/MS spectral library ( Figure 1D) 11 was performed on an illustrative compound, biotin, from the MSMS-Chooser results page (Figure S1). The illustrative MASST job can be accessed using the following link: https://gnps.ucsd.edu/ProteoSAFe/status.jsp?task=39cd886540c147e9a8a618b275e5f541.…”

Algorithmic Learning for Auto-deconvolution of GC-MS Data to Enable Molecular Networking within GNPS

“…Community adoption of GNPS has sharply increased the volume of MS data in the public domain 7 . It has also spurred new tools development (MASST 75 , FBMN 41 , ReDU 76 ) and enabled many biological discoveries. Due to the fundamental differences between CID and EI fragmentation, the GNPS infrastructure could not previously support the analysis of EI data.…”

“…Surprisingly, although GC-MS is the oldest and most established of MS-based methods, and the sheer volume of existing EI reference data accumulated over decades (far exceeding that for any other kind of MS), researchers still use decades-old data analysis strategies. We anticipate that the new GNPS community infrastructure will incentivize moving raw EI data into the public domain for data reuse, comparable to the trajectory for tandem MS 7,75,76 . GC-MS analysis within GNPS/MassIVE will lower the expertise threshold required for analysis, encourage FAIR practices 27 through reusable deposition of the data in the public domain, and promote data analysis reproducibility and “recycling” of GC-MS data.…”