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Bo dissertation final.pdf (5.69 MB)

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Novel statistical methods for evaluation of metabolic biomarkers applied to human cancer cell lines

Wang, Bo
http://rave.ohiolink.edu/etdc/view?acc_num=miami1399046331

Abstract Details

2014, Doctor of Philosophy, Miami University, Chemistry and Biochemistry.
Metabonomics is a novel tool to investigate diseases and therapeutic treatments. This dissertation describes novel statistical methods for metabonomics based on nuclear magnetic resonance (NMR) spectroscopy and their application in studying the mechanism of human cancers. Chapter 1 introduces the currently used metabonomics data interpretation methods and instruments. Chapter 2 investigated how the reproducibility of metabolite resonances measured by NMR depends on signal-to-noise ratio (SNR) and normalization methods using the coefficient of variation (CV) method. An inverse correlation was detected between SNR and CV for all normalization methods, which will aid the researchers to optimize experiments. Chapter 3 demonstrates a new potential biomarker discovery method for metabonomics studies called Standard Deviation Step Down (SDSD). Unlike most of commonly used methods, SDSD gives weight to relative metabolite concentration and is progressively more sensitive for more concentrated metabolites. Chapter 4 provides a new algorithm for Principal Components Analysis (PCA) in protein sequence analysis. The method provides a way to know which amino acid position variations are most responsible for driving separation into sub-clusters. Chapter 5 describes metabonomics study of human neuroblastoma cell line induced by Neuropeptide Y (NPY) and its Y2 receptor. High conversion of glucose into lactate in abundance oxygen (Warburg effect) and lower intracellular nutrient in NPY Y2R group was observed. NPY and Y2R may influence glycolysis, glutaminolysis and possibly TCA cycle. Chapter 6 describes role of osteopontin-a in tumor progression by studying breast cancer cell metabolites. Osteopontin-a upregulates the levels of glucose in breast cancer cells, likely through STAT3 and its transcriptional targets apolipoprotein D and IGFBP5. The splice-variant-specific metabolic effects of osteopontin add a novel aspect to the pro-metastatic functions. Chapter 7 describes the microbial community and metabolites analysis of the early stage necrotizing enterocolitis (NEC) in preterm infants. A high urinary alanine:histidine ratio was found associated with microbial community difference in the first two weeks and provided good prediction of NEC. Chapter 9 summarizes the dissertation.
Michael Kennedy (Advisor)
Neil Danielson (Committee Chair)
Carole Dabney-Smith (Committee Member)
Gary Lorigan (Committee Member)
Michael Robinson (Committee Member)
187 p.
Biochemistry; Biostatistics; Chemistry
Bioanalytical methods; Bioassays; Biological samples; Chemometrics; Statistics; NMR; Metabolomics; Metabonomics; Principal components analysis; Protein sequence analysis; Cancer biology; Metabolic regulation; Biomarker validation

Recommended Citations

Citations

  • Wang, B. (2014). Novel statistical methods for evaluation of metabolic biomarkers applied to human cancer cell lines [Doctoral dissertation, Miami University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=miami1399046331

    APA Style (7th edition)

  • Wang, Bo. Novel statistical methods for evaluation of metabolic biomarkers applied to human cancer cell lines. 2014. Miami University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=miami1399046331.

    MLA Style (8th edition)

  • Wang, Bo. "Novel statistical methods for evaluation of metabolic biomarkers applied to human cancer cell lines." Doctoral dissertation, Miami University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=miami1399046331

    Chicago Manual of Style (17th edition)

miami1399046331
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© 2014, all rights reserved.
This open access ETD is published by Miami University and OhioLINK.