Development of a Fully Automated Image Analysis Method for High Density cDNA and array CGH Microarray Based Genomic Studies

In this thesis, different techniques for image analysis of high density microarrays have been investigated. Most of the existing image analysis techniques require prior knowledge of image specific parameters and direct user intervention for microarray image quantification. The objective of this research work was to develop of a fully automated image analysis method capable of accurately quantifying the intensity information from high density microarrays images. The method should be robust against noise and contaminations that commonly occur in different stages of microarray development.

A New Gridding Technique for High Density Microarray Images Using Intensity Projection Profile of Best Sub Image

As the technologies for the fabrication of high quality microarray advances rapidly, quantification of microarray data becomes a major task. Gridding is the first step in the analysis of microarray images for locating the subarrays and individual spots within each subarray. For accurate gridding of high-density microarray images, in the presence of contamination and background noise, precise calculation of parameters is essential. This paper presents an accurate fully automatic gridding method for locating suarrays and individual spots using the intensity projection profile of the most suitable subimage. The method is capable of processing the image without any user intervention and does not demand any input parameters as many other commercial and academic packages. According to results obtained, the accuracy of our algorithm is between 95-100% for microarray images with coefficient of variation less than two. Experimental results show that the method is capable of gridding microarray images with irregular spots, varying surface intensity distribution and with more than 50% contamination

“Reconstruction of Gene Regulatory Network from Expression Profile of Plasma RNA Data of Colorectal Cancer Patients using Soft Computing Techniques”

Microarray data analysis is one of data mining tool which is used to extract meaningful information hidden in biological data. One of the major focuses on microarray data analysis is the reconstruction of gene regulatory network that may be used to provide a broader understanding on the functioning of complex cellular systems. Since cancer is a genetic disease arising from the abnormal gene function, the identification of cancerous genes and the regulatory pathways they control will provide a better platform for understanding the tumor formation and development. The major focus of this thesis is to understand the regulation of genes responsible for the development of cancer, particularly colorectal cancer by analyzing the microarray expression data. In this thesis, four computational algorithms namely fuzzy logic algorithm, modified genetic algorithm, dynamic neural fuzzy network and Takagi Sugeno Kang-type recurrent neural fuzzy network are used to extract cancer specific gene regulatory network from plasma RNA dataset of colorectal cancer patients. Plasma RNA is highly attractive for cancer analysis since it requires a collection of small amount of blood and it can be obtained at any time in repetitive fashion allowing the analysis of disease progression and treatment response.

MicroRNA–mRNA interaction network using TSK-type recurrent neural fuzzy network

MicroRNAs are short non-coding RNAs that can regulate gene expression during various crucial cell processes such as differentiation, proliferation and apoptosis. Changes in expression profiles of miRNA play an important role in the development of many cancers, including CRC. Therefore, the identification of cancer related miRNAs and their target genes are important for cancer biology research. In this paper, we applied TSK-type recurrent neural fuzzy network (TRNFN) to infer miRNA–mRNA association network from paired miRNA, mRNA expression profiles of CRC patients. We demonstrated that the method we proposed achieved good performance in recovering known experimentally verified miRNA–mRNA associations. Moreover, our approach proved successful in identifying 17 validated cancer miRNAs which are directly involved in the CRC related pathways. Targeting such miRNAs may help not only to prevent the recurrence of disease but also to control the growth of advanced metastatic tumors. Our regulatory modules provide valuable insights into the pathogenesis of cancer