title: High-resolution filtering for improved small molecule identification via GC/MS.
abstract: Gas chromatography/mass spectrometry (GC/MS) has long been considered one of the premiere analytical tools for small molecule analysis. Recently, a number of GC/MS systems equipped with high-resolution mass analyzers have been introduced. These systems provide analysts with a new dimension of information, accurate mass measurement to the third or fourth decimal place; however, existing data processing tools do not capitalize on this information. Beyond that, GC/MS spectral reference libraries, which have been curated over the last several decades, contain almost exclusively unit resolution MS spectra making integration of accurate mass data dubious. Here we present an informatic approach, called high-resolution filtering (HRF), which bridges this gap. During HRF, high-resolution mass spectra are assigned putative identifications through traditional spectral matching at unit resolution. Once candidate identities have been assigned, all unique combinations of atoms from these candidate precursors are generated and matched to m/z peaks using narrow mass tolerances. The total amount of measured signal that is annotated is used as a metric of plausibility for the presumed identification. Here we demonstrate that the HRF approach is both feasible and highly specific toward correct identifications.
authors.affiliation: †Genome Center of Wisconsin, Madison, Wisconsin 53706, United States.|‡Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Kwiecien
authors.affiliation: †Genome Center of Wisconsin, Madison, Wisconsin 53706, United States.|‡Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Bailey
authors.affiliation: †Genome Center of Wisconsin, Madison, Wisconsin 53706, United States.|‡Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
authors.forename: Matthew J P
authors.initials: MJ
authors.lastname: Rush
authors.affiliation: §Thermo Fisher Scientific, Austin, Texas 78728, United States.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Cole
authors.affiliation: †Genome Center of Wisconsin, Madison, Wisconsin 53706, United States.|‡Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
authors.forename: Arne
authors.initials: A
authors.lastname: Ulbrich
authors.affiliation: †Genome Center of Wisconsin, Madison, Wisconsin 53706, United States.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Hebert
authors.affiliation: †Genome Center of Wisconsin, Madison, Wisconsin 53706, United States.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Westphall
authors.affiliation: †Genome Center of Wisconsin, Madison, Wisconsin 53706, United States.|‡Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Coon
mesh_terms: D005374:Filtration; D008401:Gas Chromatography-Mass Spectrometry; D004364:Pharmaceutical Preparations / Q000652:urine; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000302:isolation & purification; D016482:Urinalysis / Q000295:instrumentation / Q000379:methods*
chemical_list: D004364:Pharmaceutical Preparations; D054852:Small Molecule Libraries