title: Informatics for cross-sample analysis with comprehensive two-dimensional gas chromatography and high-resolution mass spectrometry (GCxGC-HRMS).
abstract: This paper describes informatics for cross-sample analysis with comprehensive two-dimensional gas chromatography (GCxGC) and high-resolution mass spectrometry (HRMS). GCxGC-HRMS analysis produces large data sets that are rich with information, but highly complex. The size of the data and volume of information requires automated processing for comprehensive cross-sample analysis, but the complexity poses a challenge for developing robust methods. The approach developed here analyzes GCxGC-HRMS data from multiple samples to extract a feature template that comprehensively captures the pattern of peaks detected in the retention-times plane. Then, for each sample chromatogram, the template is geometrically transformed to align with the detected peak pattern and generate a set of feature measurements for cross-sample analyses such as sample classification and biomarker discovery. The approach avoids the intractable problem of comprehensive peak matching by using a few reliable peaks for alignment and peak-based retention-plane windows to define comprehensive features that can be reliably matched for cross-sample analysis. The informatics are demonstrated with a set of 18 samples from breast-cancer tumors, each from different individuals, six each for Grades 1-3. The features allow classification that matches grading by a cancer pathologist with 78% success in leave-one-out cross-validation experiments. The HRMS signatures of the features of interest can be examined for determining elemental compositions and identifying compounds.
authors.affiliation: University of Nebraska - Lincoln, NE 68588-0115, USA. reich@cse.unl.edu
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Reichenbach
authors.forename: Xue
authors.initials: X
authors.lastname: Tian
authors.forename: Qingping
authors.initials: Q
authors.lastname: Tao
authors.forename: Edward B
authors.initials: EB
authors.lastname: Ledford
authors.forename: Zhanpin
authors.initials: Z
authors.lastname: Wu
authors.forename: Oliver
authors.initials: O
authors.lastname: Fiehn
mesh_terms: D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D048088:Informatics / Q000379:methods*; D013223:Statistics as Topic / Q000379:methods*