Introduction to Metabolomics











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This is the first module in the 2016 Informatics and Statistics for Metabolomics workshop hosted by the Canadian Bioinformatics Workshops. This lecture is by David Wishart from University of Alberta (https://tmicwishartnode.ca/). • How it Begins by Kevin MacLeod is licensed under a Creative Commons Attribution license (https://creativecommons.org/licenses/...) • Source: http://incompetech.com/music/royalty-... • Artist: http://incompetech.com/ • Table of Contents: • 00:10 - • 00:34 - Learning Objectives • 01:57 - Schedule • 02:15 - The Pyramid of Life • 08:07 - What is Metabolomics? • 08:47 - What is a Metabolite? • 10:58 - What is a Metabolome? • 12:27 - Different Metabolomes • 14:48 - Human Metabolomes (2015) • 17:27 - Theoretical Human Metabolomes • 19:06 - Why is Metabolomics Important? • 19:17 - Small Molecules Count… • 23:53 - Metabolites Are the Canaries of the Genome • 24:20 - Metabolomics is More Time Sensitive Than Other “Omics” • 25:51 - Metabolism is “Understood” • 26:16 - The Metabolome is Connected to all other “Omes” • 27:04 - The Metabolome is Connected to All Other “Omes” • 28:04 - Metabolomics Enables Systems Biology • 28:37 - Metabolomics Applications • 29:08 - Metabolomics Methods • 29:45 - Metabolomics Workflow • 35:03 - Comparing “Omics” Coverage • 36:11 - Why Metabolomics is Difficult • 37:08 - Metabolomics Technologies • 38:10 - Chromatography • 38:15 - Chromatography • 39:18 - High Pressure (Performance) Liquid Chromatography - HPLC • 39:58 - HPLC Modalities • 40:56 - HPLC Columns • 41:30 - Reverse Phase Column • 42:32 - HPLC Separation Efficiency • 43:08 - HPLC Schematic • 43:49 - Gradient HPLC Schematic • 44:27 - HPLC of a Biological Mixture • 45:16 - Gas Chromatography • 45:42 - Gas Chromatography • 46:27 - TMS Derivatization • 48:12 - Gas Chromatography • 48:43 - GC-Columns • 49:12 - Retention Time/Index • 51:15 - Compound Identification and Quantification • 52:03 - GC-MS Chromatogram of a Biological Mixture • 52:23 - Mass Spectrometry • 52:44 - Typical Mass Spectrometer • 52:51 - MS Principles • 53:18 - Mass Spectrometry • 53:42 - Different Types of MS • 54:12 - Masses in MS • 55:14 - Isotopic Distributions • 56:13 - Isotopic Distributions • 56:52 - Mass Spec Principles • 57:15 - Typical Mass Spectrum • 57:42 - Typical Mass Spectrum • 58:08 - Typical Mass Spectrum • 58:35 - Typical Mass Spectrum • 58:43 - Resolution Resolving Power • 59:00 - Resolution in MS • 59:44 - Resolution in MS • 01:00:21 - Resolution/Resolving Power • 01:01:08 - Mass Spectrometer Schematic • 01:01:53 - Different Ionization Methods • 01:03:56 - Electron Impact Ionization Source • 01:04:43 - Electron Impact Ionization • 01:05:14 - EI Fragmentation of CH3OH • 01:05:43 - Electron Impact MS of CH3OH • 01:06:11 - Soft Ionization Methods • 01:06:39 - Electrospray (Detail) • 01:07:18 - Electrospray (Detail) • 01:08:14 - Electrospray Ionization • 01:08:38 - Electrospray Ionization • 01:08:55 - Electrospray Ionization • 01:09:27 - Mass Spectrometer Schematic • 01:10:27 - Different Types of Mass Analyzers • 01:11:54 - MS Mass Accuracy • 01:12:47 - Mass Chromatograms • 01:13:43 - Mass Chromatograms of Biological Mixtures • 01:14:13 - NMR Spectroscopy • 01:15:10 - Explaining NMR • 01:15:55 - Principles of NMR • 01:17:04 - Protons (and other nucleons) Have Spin • 01:17:46 - Each Spinning Proton is Like a “Mini-Magnet” • 01:17:58 - Principles of NMR • 01:19:23 - Bigger Magnets are Better • 01:19:59 - A Modern NMR Instrument • 01:20:37 - NMR Magnet • 01:21:28 - NMR Magnet Cross-Section • 01:22:23 - An NMR Probe • 01:22:59 - NMR Sample Probe Coil • 01:23:12 - 1H NMR Spectra Exhibit... • 01:24:30 - Chemical Shifts • 01:24:51 - Characteristic Chemical Shifts • 01:25:10 - Assigning Simple NMR Spectra • 01:25:58 - Assigning Simple NMR Spectra • 01:26:15 - NMR Spectra Need “Fixin’” • 01:26:53 - NMR Spectra Need “Fixin’” • 01:27:18 - NMR Spectrum of a Biological Mixture • 01:27:47 - Technology Sensitivity • 01:30:00 - Comparison • 01:30:21 - Comparison • 01:31:04 - What’s Possible • 01:31:45 - 2 Routes to Metabolomics • 01:32:11 - Profiling (Untargeted) • 01:32:59 - Quantitative (Targeted) • 01:35:59 - From Spectra to Lists • 01:36:15 - From Lists to Pathways • 01:36:31 - From Pathways Lists to Models Biomarkers • 01:36:45 - Key Informatics Challenges in Metabolomics • 01:36:59 -

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