Ankara : The Department of Molecular Biology and Genetics and the Graduate School of Engineering and Science of Bilkent University, 2011.Thesis (Ph. D.) -- Bilkent University, 2011.Includes bibliographical references leaves 99-115.microRNAs, small non-coding RNA molecules with important roles in
cellular machinery, target mRNAs for silencing by binding generally to their 3’ UTR
sequences via partial base complementation. Thus, microRNAs with similar
sequences also might exhibit expression and/or functional similarities. In this study, a
modular tool, mESAdb (http://konulab.fen.bilkent.edu.tr/mirna/), was developed
allowing for multivariate analysis of sequences and expression of microRNAs from
multiple taxa. Its framework comprises PHP, JavaScript, packages in the R language,
and a database storing mature microRNA sequences along with microRNA targets
and selected expression data sets for human, mouse and zebrafish. mESAdb allows
for: (i) mining of microRNA expression data sets for subsets of microRNAs selected
manually or by a sequence motif; (ii) pair-wise multivariate analysis of expression
data sets within and between taxa; and (iii) association of microRNA subsets with
annotation databases, HuGE Navigator, KEGG and GO. mESAdb also permits user
specified dataset upload for these analyses. Herein, utility of mESAdb was illustrated
using different datasets and case studies. First, it was shown that microRNAs
carrying the embryonic stem cell specific seed sequence, ‘AAGTGC’, were able to
discriminate between normal and tumor tissues from hepatocellular carcinoma
patients using dataset GSE10694. Second, mRNA targets of a set of liver specific
microRNAs were annotated with human diseases based on HuGE Navigator. Third,
the similarity between mouse and human tissue specificity of a given set of microRNAs was demonstrated. Forth, CHRNA5 targeting microRNAs were
associated with estrogen receptor status in breast cancer using dataset GSE15885.
Finally, a related tool under development for mRNA arrays planned for integration
with mESAdb was presented.Kaya, Koray DoğanPh.D