Functional Characterization of the NSF1 (YPL230W) Gene using Correlation Clustering and Genetic Analysis in Saccharomyces Cerevisiae

• Main Author: Bessonov, Kyrylo
• Other Authors: van der Merwe, George
• Language: en
• Published: 2012
• Subjects: microarray analysis; NSF1 ( YPL230W ); correlation clustering; fermentation stress; novel gene functions; functional networks; clustering
• Online Access: http://hdl.handle.net/10214/3251

High throughput technologies such as microarrays and modern genome sequencers produce enormous amounts of data that require novel data processing. This thesis proposes a method called Interdependent Correlation Cluster (ICC) to analyze the relations between genes represented by microarray data that are conditioned on a specific target gene. Based on Correlation Clustering, the proposed method analyzes a large set of correlation values related to the gene expression profiles extracted from given microarray datasets. The proposed method works on any size microarray datasets and could be applied to any target gene. In this study the selected target gene, NSF1 /USV1 / YPL230W, encodes a poorly characterized C2H2 zinc finger transcription factor (TF) involved in stress responses in yeast. The method is successful in the identification of novel NSF1 functional roles during fermentation stress conditions in the M2 industrial yeast strain. The new identified functions include regulation of energy and sulfur metabolism, protein synthesis, ribosomal assembly and protein trafficking as well as other processes. NSF1 involvement in sulfur metabolism was experimentally confirmed using biological laboratory techniques. Importantly, implication of NSF1 in sulfur metabolism regulation has highly relevant implications to wine and beer production industries concerned with production of compounds having sulfur-like off odour (SLO) and toxic properties. The correlation clustering also provides a means of understanding complex interactions existing between genes. === The pdf file contains numerous hyperlinks and bookmarks to facilitate navigation. This thesis will be of interest to those working with topics such as data mining of microarray data, novel gene function discovery and prediction, and genome-wide responses to fermentation stresses. === Ministry of Training, Colleges and Universities of Ontario (Ontario Graduate Scholarship and Ontario Graduate Scholarships in Science and Technology); The Natural Sciences and Engineering Research Council of Canada (NSERC)