Table 2 Advanced molecular networking tools for metabolite annotation of LC-MS/MS data

IIMN

A tool integrates chromatographic peak shape correlation analysis into molecular networks to connect and collapse different ion species of the same molecule.

(Schmid et al. 2021)

NetID

An algorithm optimizes a network of mass spectrometry peak connections based on MS1 mass differences corresponding to the gain or loss of relevant chemical moieties, and MS2 spectral similarity.

(Chen et al. 2021)

Qemistree

A tree-based approach for computing and representing chemical features from tandem MS-based metabolomics studies, which is based on the hierarchical organization of molecular fingerprints predicted from MS/MS fragmentation spectra.

(Tripathi et al. 2021)

FBMN

A method that bridges popular MS data processing tools for LC-MS/MS and molecular networking analysis on GNPS, enabling the characterization of isomers, incorporation of relative quantification, and integration of ion mobility data.

(Nothias et al. 2020)

CliqueMS

A computational tool that annotates redundant MS1 features by constructing a similarity network between coelution profiles and a calculated natural frequency of adduct formation observed in real complex biological samples and pure compounds, which produces accurate annotations for a single MS1 spectrum.

(Senan et al. 2019)

MetWork

An annotation propagation tool, which based on MS2 data, organized in molecular network, a collaborative library of reactions, and a MS2 spectra prediction module.

(Beauxis et al. 2019)

MetDNA

A metabolic reaction network-based recursive algorithm that characterizes initial seed metabolites with MS2 spectra, and utilizes their experimental MS2 spectra as surrogate spectra to annotate their reaction-paired neighbor metabolites.

(Shen et al. 2019)

SIRIUS 4

A tool integrates high-resolution isotope pattern analysis and fragmentation trees to provide an assessment of molecular structures from MS2 data for large datasets and propagation of annotation through molecular networks.

(Duhrkop et al. 2019)

MolNetEnhancer

A software package that unites the output of several tools, including mass spectral molecular networking, unsupervised substructure discovery, and in silico structure annotation to illuminate structural details for each fragmentation spectrum.

(Ernst et al. 2019)

DEREPLICATOR +

A tool for search the entire GNPS and identifies variants of known metabolites using molecular networking, which improves the identification of peptidic natural products, polyketides, terpenes, benzenoids, alkaloids, flavonoids, etc.

(Mohimani et al. 2018)

NAP

An on-line tool that uses a combination of molecular networks, based on spectral similarity, together with in silico fragmentation, to enable the scientific community to strengthen their MS annotations.

(da Silva et al. 2018)

DEREPLICATOR

A new dereplication algorithm that searches MS/MS spectral datasets against the database of peptidic natural products (PNPs), which enables high-throughput PNPs identification based on molecular networking.

(Mohimani et al. 2017)

MS2LDA

An unsupervised method that extracts common patterns of mass fragments and neutral losses-Mass2Motifs from the collection of fragmentation spectra, which can be used to annotate molecules.

(van der Hooft et al. 2016)

ISDB

An innovative dereplication strategy based on the combination of molecular networking with an extensive in-silico MS2 fragmentation database of natural products.

(Allard et al. 2016)

GNPS

An open-access knowledge base for community-wide organization and sharing of raw, processed or identified MS2 spectrometry data.

(Wang et al. 2016)