BIOINFORMATICS APPROACHES TO ASSOCIATE SINGLE NUCLEOTIDE POLYMORPHISMS WITH HUMAN DISEASES ACCORDING TO THEIR PATHWAY RELATED CONTEXT

Burcu Bakir-Güngör

Biological Sciences and Bioengineering, PhD Thesis, 2012 

Thesis Jury

Assoc. Prof. O.Uğur Sezerman (Thesis Supervisor), Prof. Uğur Özbek, 

Prof. Selim Çetiner, Asst. Prof. Murat Çokol, Assoc. Prof. Devrim Gözüaçık 

Date &Time: June 8th, 2012 - 11:00

Place: G032

Keywords: Genome Wide Association Studies (GWAS), Single Nucleotide Polymorphisms (SNPs), human complex diseases, pathways, protein-protein interaction networks

Abstract

Genome-wide association studies (GWAS) with millions of single nucleotide polymorphisms (SNPs) are popular strategies to reveal the genetic basis of human complex diseases. Despite many successes of GWAS, it is well recognized that new analytical approaches have to be integrated to achieve their full potential. In this thesis, starting with a list of SNPs, found to be associated with disease in GWAS, we have developed a novel methodology to devise functionally important KEGG pathways through the identification of genes within these pathways, where these genes are obtained from SNP analysis. Our methodology is based on functionalization of important SNPs to identify effected genes and disease related pathways. We have tested our methodology on rheumatoid arthritis, epilepsy, intracranial aneurysm and Behcet’s disease datasets. With the whole-genome sequencing on the horizon, we show that the full potential of GWAS can be achieved by integrating prior knowledge from functional properties of a SNP and pathway-oriented analysis via protein-protein interaction networks.