Topic modeling for untargeted substructure exploration in metabolomics

Justin Johan Jozias van der Hooft, Joe Wandy, Michael P Barrett, Karl E V Burgess, Simon Rogers

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

The potential of untargeted metabolomics to answer important questions across the life sciences is hindered because of a paucity of computational tools that enable extraction of key biochemically relevant information. Available tools focus on using mass spectrometry fragmentation spectra to identify molecules whose behavior suggests they are relevant to the system under study. Unfortunately, fragmentation spectra cannot identify molecules in isolation but require authentic standards or databases of known fragmented molecules. Fragmentation spectra are, however, replete with information pertaining to the biochemical processes present, much of which is currently neglected. Here, we present an analytical workflow that exploits all fragmentation data from a given experiment to extract biochemically relevant features in an unsupervised manner. We demonstrate that an algorithm originally used for text mining, latent Dirichlet allocation, can be adapted to handle metabolomics datasets. Our approach extracts biochemically relevant molecular substructures ("Mass2Motifs") from spectra as sets of co-occurring molecular fragments and neutral losses. The analysis allows us to isolate molecular substructures, whose presence allows molecules to be grouped based on shared substructures regardless of classical spectral similarity. These substructures, in turn, support putative de novo structural annotation of molecules. Combining this spectral connectivity to orthogonal correlations (e.g., common abundance changes under system perturbation) significantly enhances our ability to provide mechanistic explanations for biological behavior.

Original languageEnglish
Pages (from-to)13738-13743
Number of pages6
JournalProceedings of the National Academy of Sciences (PNAS)
Issue number48
Early online date16 Nov 2016
Publication statusPublished - 29 Nov 2016

Keywords / Materials (for Non-textual outputs)

  • algorithms
  • databases
  • metabolomics
  • tandem mass spectrometry
  • workflow
  • factual


Dive into the research topics of 'Topic modeling for untargeted substructure exploration in metabolomics'. Together they form a unique fingerprint.

Cite this