Searching molecular structure databases with tandem mass spectra using CSI:FingerID

Proc Natl Acad Sci U S A. 2015 Oct 13;112(41):12580-5. doi: 10.1073/pnas.1509788112. Epub 2015 Sep 21.

Abstract

Metabolites provide a direct functional signature of cellular state. Untargeted metabolomics experiments usually rely on tandem MS to identify the thousands of compounds in a biological sample. Today, the vast majority of metabolites remain unknown. We present a method for searching molecular structure databases using tandem MS data of small molecules. Our method computes a fragmentation tree that best explains the fragmentation spectrum of an unknown molecule. We use the fragmentation tree to predict the molecular structure fingerprint of the unknown compound using machine learning. This fingerprint is then used to search a molecular structure database such as PubChem. Our method is shown to improve on the competing methods for computational metabolite identification by a considerable margin.

Keywords: bioinformatics; machine learning; mass spectrometry; metabolomics; small compound identification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Databases, Protein*
  • Humans
  • Machine Learning*
  • Mass Spectrometry*
  • Metabolomics*