title: Chemical structure identification in metabolomics: computational modeling of experimental features.
abstract: The identification of compounds in complex mixtures remains challenging despite recent advances in analytical techniques. At present, no single method can detect and quantify the vast array of compounds that might be of potential interest in metabolomics studies. High performance liquid chromatography/mass spectrometry (HPLC/MS) is often considered the analytical method of choice for analysis of biofluids. The positive identification of an unknown involves matching at least two orthogonal HPLC/MS measurements (exact mass, retention index, drift time etc.) against an authentic standard. However, due to the limited availability of authentic standards, an alternative approach involves matching known and measured features of the unknown compound with computationally predicted features for a set of candidate compounds downloaded from a chemical database. Computationally predicted features include retention index, ECOM50 (energy required to decompose 50% of a selected precursor ion in a collision induced dissociation cell), drift time, whether the unknown compound is biological or synthetic and a collision induced dissociation (CID) spectrum. Computational predictions are used to filter the initial "bin" of candidate compounds. The final output is a ranked list of candidates that best match the known and measured features. In this mini review, we discuss cheminformatics methods underlying this database search-filter identification approach.
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, 69 N Eagleville Rd, Storrs, CT 06269, United States.
authors.forename: Lochana C
authors.initials: LC
authors.lastname: Menikarachchi
authors.affiliation: Department of Computer Science & Engineering, University of Connecticut, 371 Fairfield Road, Unit 2155 Storrs, CT 06269, United States.
authors.forename: Mai A
authors.initials: MA
authors.lastname: Hamdalla
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, 69 N Eagleville Rd, Storrs, CT 06269, United States.
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Hill
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, 69 N Eagleville Rd, Storrs, CT 06269, United States.
authors.forename: David F
authors.initials: DF
authors.lastname: Grant
keywords: HPLC; QSPR; ion mobility; mass spectrometry; metabolomics; retention index