Alignment, Denoising, and Identification in Metabolomics

• Main Authors: Tsung-Jung Ho, 何宗融
• Other Authors: 曾宇鳳
• Format: Others
• Language: zh-TW
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/35938680734849781329

碩士 === 國立臺灣大學 === 資訊工程學研究所 === 99 === This dissertation presents two developed algorithms for solving computational problems of detecting small molecules in the field of metabolomics analysis and toxicological screening. In the first part of this dissertation, we present the tool － Chromaligner, which is a tool for chromatogram alignment to align retention time for chromatographic methods coupled to spectrophotometers such as high performance liquid chromatography and capillary electrophoresis for metabolomics works. Chromaligner resolves peak shifts by a constrained chromatogram alignment. For a collection of chromatograms and a set of defined peaks, Chromaligner aligns the chromatograms on defined peaks using correlation optimized warping (COW). Chromaligner is faster than the original COW algorithm by k2 times, where k is the number of defined peaks in a chromatogram. It also provides alignments based on known component peaks to reach the best results for further chemometric analysis. In the second part of this dissertation, we present the tool － TIPick. Liquid Chromatography - Time of Flight mass spectrometry has become an important technique in toxicological screening and metabolomic analysis. We hereby provide an effective algorithm, TIPick, for target analysis to accurately and sensitively detect target compounds in complex samples. TIPick comprises two major steps: background subtraction and peak picking. By subtracting the blank chromatogram, TIPick is able to eliminate chemical signals appearing in blank injections. TIPick utilizes the length and intensity of chromatographic peaks to perform peak enhancement and peak picking; thus, it is able to detect low-intensity or split peaks that may arise from either instrumental saturation or a mathematical background subtraction algorithm. TIPick is able to detect all peaks even the tailing or fronting peaks without pre-assuming peak shape. Furthermore, TIPick uses duplicate injections to enhance the signals of peaks, which improves peak detection power. TIPick can generate the extracted ion chromatograms for target m/z and automatically provide the total peak table of the sample. TIPick has successfully constructed the NTU MetaCore standard library and facilitated toxicological screening.