Chemometric methods for microarray data analysis and their application to leukemia subtype identification [Elektronische Ressource] / vorgelegt von Eric Andrés Frauendorfer

Kj

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• Gesundheit

Informations

• Publié par: westfalische_wilhelms-universitat_munster
• Publié le: 01 janvier 2004
• Nombre de lectures: 23
• Langue: Deutsch
• Poids de l'ouvrage: 4 Mo

Extrait

Analytische Chemie










Chemometric methods for microarray
data analysis and their application
to leukemia subtype identification










Inaugural-Dissertation
zur Erlangung des Doktorgrades
der Naturwissenschaften im Fachbereich Chemie und Pharmazie
der Mathematisch-Naturwissenschaftlichen Fakultät
der Westfälischen Wilhelms-Universität Münster









vorgelegt von
Eric Andrés Frauendorfer
aus Caracas
- 2004 -


























Dekan: Prof. Dr. J. Leker
Erster Gutachter: Prof. Dr. K. Cammann
Zweiter Gutachter: Prof. Dr. J. von Frese
Tag der mündlichen Prüfungen: 12., 14., 16.07.2004
Tag der Promotion: 16.07.2004Content I
Table of Contents

1 Introduction.................................................................................................... 1
2 Aims & Scope ................................................................................................. 3
3 Theory............................................................................................................. 4
3.1 Nucleic Acid: Structure and Function.................................................................... 4

3.2 Gene Expression.......................................5

3.3 Cancer....................................................................................................................... 6
3.3.1 Overview ............................................................................................................................................ 6
3.3.2 Leukemia ............................................................................................................................................ 9
3.3.2.1 Introduction ................................................................................................................................... 9
3.3.2.2 Diagnosis ..................................................................................................................................... 11
3.3.2.3 Treatment and the significance of molecular differences of ALL subtypes.............................. 13

3.4 DNA Biosensors...................................................................................................... 14
3.4.1 Definition and Overview.................................................................................................................. 14
3.4.2 DNA Microarray Technology.......................................................................................................... 15
3.4.2.1 Overview ..................................................................................................................................... 15
3.4.2.2 Spotted microarrays..................................................................................................................... 15
3.4.2.3 Microarrays created by photolithography................................................................................... 16
3.4.2.4 Medical Applications of DNA-biosensors.................................................................................. 17
3.4.3 Affymetrix Microarrays ................................................................................................................... 18
3.4.3.1 Physical construction................................................................................................................... 18
3.4.3.2 Calculation of gene expressions.................................................................................................. 20

3.5 Chemometrics.........................................................................................................21
3.5.1 Introduction ...................................................................................................................................... 21
3.5.2 The role of chemometrics in microarray experiments..................................................................... 22
3.5.3 Pre-processing .................................................................................................................................. 23
3.5.4 Cluster analysis – hierarchical clustering ........................................................................................ 24
3.5.5 Principal component analysis .......................................................................................................... 26
3.5.5.1 Introduction ................................................................................................................................. 26
3.5.5.2 Eigenvalues, eigenvectors........................................................................................................... 27
3.5.5.3 Calculations in Principal Component Analysis.......................................................................... 28
3.5.6 Cross Validation............................................................................................................................... 28
3.5.7 Support Vector Machines (SVM).................................................................................................... 29
3.5.8 Gene selection Methods................................................................................................................... 31
3.5.8.1 Gene shaving ............................................................................................................................... 31
3.5.8.2 Significance analysis of microarrays (SAM).............................................................................. 32
3.5.8.3 Predication Analysis of Microarrays (PAM).............................................................................. 34
3.5.8.4 Fisher’s Ratio............................................................................................................................... 35
3.5.9 Gene expression summary algorithms............................................................................................. 36
3.5.9.1 Affymetrix MicroArraySuit (MAS) 5.0 algorithm..................................................................... 36
3.5.9.2 MAS, perfect match only ............................................................................................................ 37
3.5.9.3 Li – Wong Model ....................................................................................................................... 37
3.5.9.4 RMA Model................................................................................................................................ 37

4 Method development ................................................................................... 38
4.1 Databases.................................................................................................................38
4.1.1 Introduction ...................................................................................................................................... 38
4.1.2 Microarray Data Management System ............................................................................................ 39
Content II
4.2 Analysis of the raw data provided by the scanner .............................................. 41

4.3 Artifact detection............................................................................44
4.3.1 Medianchip images for artifact detection. .......................................................................................45
4.3.2 Artifact detection algorithm............................................................................................................. 46

4.4 Background correction..........................................................................................51
4.4.1 Background in Affymetrix Microarrays .......................................................................................... 51
4.4.2 Background estimation using the checkerboard pattern ................................................................. 52
4.4.3 Interpolation using the Auto-leveling Method (ALM) .................................................................. 55
4.4.4 Thin-plate interpolation.................................................................................................................... 55
4.4.4.1 Theory.......................................................................................................................................... 55
4.4.4.2 Background subtraction............................................................................................................... 56
4.4.5 Application of a scaling factor......................................................................................................... 62

4.5 Probe Sequence Development ........................