August 7, Tuesday
12:00 – 13:00
Algorithms for MicroRNA Target Prediction and Post-Transcriptional Gene Regulation in Host-Viral Interactions
Computer Science seminar
Lecturer : Isana Veksler
Affiliation : CS, BGU
Location : 202/37
Host : Dr. Aryeh Kontorovich
MicroRNAs (miRNAs) are an abundant class of small non-coding RNAs that
can affect gene expression by post-transcriptional regulation of
mRNAs. miRNAs have been shown to play important roles in various
cellular and pathogenic processes. Some viral organisms also encode
miRNAs, a fact that contributes to the complex interactions between viruses and their hosts.
miRNAs down-regulate translation of genes via imperfect binding of the
miRNA to a specific site or sites on their coding transcripts. A
critical step in miRNA functional studies is to identify the target
genes that are directly regulated by miRNAs. The current target
prediction tools have two major limitations. First, they are time consuming for large datasets.
Second, they are noisy and predict an excess of targets for each miRNA.
To overcome the first limitation, we developed our own method for
target prediction, which extends the "threshold all-against-all"
sequence alignment algorithm. To get over the second limitation, we
developed methods, related to bi-clustering, that combine target
prediction results with new host-viral post transcriptional regulation
modes and additional information sources, and narrow the list of target genes to more reliable candidates.
Our algorithm, called bi-targeting, searches for modules of miRNAs
(host and viral) and their common host target genes that have a
similar biological function. We applied it to the discovery of modules
consisting of human and Epstein-Barr virus (EBV) miRNAs and human
genes, in a cooperating mode of regulation.
Later we relaxed the bi-targeting algorithm to compute quasi-modules,
where many more interactions were captured and reported. We used our
new relaxed bi-targeting algorithm to study the compensating
regulation of miRNAs in Human cytomegalovirus (HCMV) infection, using
new expression data of miRNAs in HCMV infected vs. un-infected cells.
Since not much is known about the function of viral miRNAs, finding
modules that link the viral miRNAs and the human miRNAs, might help in
understanding the role of miRNAs in host-viral interactions.
Furthermore, since the identification and validation of miRNA targets
remains a hard problem, focusing on small sets of miRNAs and their
effects on particular biological pathways may give a significant
advantage in target identification.