The Biological Sample Classification Using Gene Expression Data

Dedicated to my family

Acknowledgements

I would like to send my faithfull and deepest gratitude to my supervisor,

Asso. Prof. Ha Quang Thuy who is always behind me and give me

valuable encouragement, advices not only in my research activities but

also in daily life. This thesis must have been imcomplete if without

enthusiastical help and encouragement of Prof. Arndt von Haeseler from

Center for Integrative Bioinformatics Vienna-CIBIV, Austria. It’s very

kind of you to offer me an opportunity to do the research on

Bioinformatics field of study.

Thanks to all members of the Data Mining research group for the seminar

topics held periodically from which I’ve gotten lot of meaningfull

knowledge. Anyway, thanks to the Information Systems Department,

COLTECH, VNUH for it’s friendly and suitable to doing the scientific

research environment. This work was supported in part by the National

Project "Developing content filter systems to support management and

implementation public security - ensure policy" and the MoST-203906

Project "Information Extraction Models for discovering entities and

semantic relations from Vietnamese Web pages".

Finally, I would like to thank Mr. Le Si Vinh and Mr. Bui Quang Minh

for their continued help during the time of implementing this thesis.

FOREWORD .................................................................................................1

CHAPTER 1...................................................................................................3

INTRODUCTION TO GENE EXPRESSION DATA...............................3

1.1. GENE EXPRESSION ................................................................................3

1.2. DNA MICROARRAY EXPERIMENTS .......................................................5

1.3. HIGH-THROUGHPUT MICROARRAY TECHNOLOGY .............................8

1.4. MICROARRAY DATA ANALYSIS ...........................................................12

1.4.1. Pre-processing step on raw data.................................................14

1.4.1.1 Processing missing values..............................................................14

1.4.1.2. Data transformation and Discretization ........................................15

1.4.1.3. Data Reduction...............................................................................16

1.4.1.4. Normalization.................................................................................17

1.4.2. Data analysis tasks ......................................................................18

1.4.2.1. Classification on gene expression data.........................................18

1.4.2.2. Feature selection ...........................................................................21

1.4.2.3. Performance assessment ...............................................................21

1.5. RESEARCH TOPICS ON CDNA MICROARRAY DATA ............................22

CHAPTER 2.................................................................................................25

GRAPH BASED RANKING ALGORITHMS WITH GENE

NETWORKS................................................................................................25

2.1. GRAPH BASED RANKING ALGORITHMS .............................................25

2.2. INTRODUCTION TO GENE NETWORK..................................................29

2.2.1. The Boolean Network Model .......................................................30

2.2.2. Probabilistic Boolean Networks...................................................31

2.2.3. Bayesian Networks........................................................................31

2.2.4. Additive regulation models...........................................................33

CHAPTER 3.................................................................................................35

REAL DATA ANALYSIS AND DISCUSSION .......................................35

3.1. THE PROPOSED SCHEME FOR GENE SELECTION IN SAMPLE

CLASSIFYING PROBLEM..............................................................................35

3.2. DEVELOPING ENVIRONMENT..............................................................37

3.3. ANALYSIS RESULTS .............................................................................38

REFERENCES ............................................................................................43