The Retention Time Alignment for Nontargeted LC/MS Analysis Using Kernel Density Estimation with a Novel Bandwidth Estimator and Phase Correction of Metabolomic 1D 1H-NMR Spectra
Date Issued
2015
Date
2015
Author(s)
Liu, Jia-Wei
Abstract
This dissertation presents two developed algorithms for solving computational problems of detecting small molecules in the field of metabolomics analysis. In the first part of this dissertation, we present the tool – LAKE, which is a tool for detected peak alignment to align retention time for chromatographic methods coupled to spectrophotometers such as high performance liquid chromatography for metabolomics works. The existed tools for retention time correction still can’t properly aligning retention times of detected peaks from multiple batches and some detected peaks are left misalignment. LAKE resolves peak shifts from high data similarity to low data similarity. In each turn, detected peaks would be clustered in mass-over-charged (m/z) dimension and then retention time (RT) dimension. For each m/z-RT cluster, bandwidth used in RT density estimation with kernel density estimation (KDE) is estimated with bandwidth selector. At the end of each turn of retention time shift resolution, the m/z and RT of detected peaks would be updated with average m/z and average RT of the m/z-RT group before next turn of detected peak alignment. LAKE can be applied to aligning retention time from mixed exogenic compounds samples, multiple exogenic compounds added in biofluid samples and complicate endogenous compounds contained metabolomics samples in multiple batches. In the second part of this dissertation, we present the tool – PHASION, which is a tool for automatic phase correction on multiple 1D proton nuclear magnetic resonance (1H-NMR) spectra for metabolomics works. The phase error is an unavoidable error happened when FID signal is recorded, after Fourier transformed into spectrum mixed with phase error. The phase correction is to find zeroth-order and first-order phase error to make misphased spectrum into phase-corrected spectrum before any further data processing. Current 1D 1H-NMR phase correction methods usually require manual parameter and filter tuning by experienced users to obtain desirable results from complex metabolomics spectra – thus becoming prone to correction variation and biased quantification. We present a novel alternative method, PHASION, for automatically estimating the phase angles of 1D 1H-NMR metabolomics data. PHASION finds optimal phase angles by calculating proposed objective score for relative stable segments of spectrum and calculates the score for baseline of spectrum phased with phase angles (PH0, PH1) and approach to the optimal phase angles for the spectrum with Nelder-Mead Simplex Optimizer.
Subjects
liquid chromatography/mass spectrometry
retention time alignment
kernel density estimation
proton nuclear magnetic resonance spectrum
phase correction
metabolomics
Type
thesis
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