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Transcript of PhDseminar
Department of Computer Science
Doctor of Philosophy Defense
Supervisor: Prof. Reda Alhajj Biological Network-based Approaches to The
Functional Analysis of miRNAs in Prostate Cancer Background
-A voyage inside the cell
-From lab experiments to ‘omes puzzle
-miRNA biology: from C.elegans to cancer therapeutic targets From molecular biology to 'omes puzzle miRNAs are part of the big picture The End
Thank you Network-based approaches for the functional characterization of miRNAs: a prostate cancer case study
-Integrating miRNA-target and protein networks for context-specific miRNA regulation
-Coordinate miRNA regulation of functional protein sets
-Functional modulation between miRNAs and protein networks
-Context-specific miRNA regulation for miRNA gene set functional enrichment analysis
-Network-based miRNA enrichment Motivation
-miRNA systems biology: cross-talk between -miRNAs and biological networks
-Research question formulation -Overall contribution
Summary and future work genomes proteomes interactome The path to functional systems biology In the scope of this thesis I focused on miRNAs miRNA biology miRNA research line 2011 2007 2004 2002 2000 1993 Integrating expression data and miRNA-target networks -miRNA profiling
Computational miRNA target prediction
-miRNA as diagnostic and prognostic biomarkers miRNA discovery in human miRNA alteration in cancer cells miRNA discovery in C.elegan -miRNA decoys: the power of gene modulation
-miRNA systems biology: the big picture miRNA-target interactions: what is next? Identify regulatory miRNAs from dysregulated gene sets and build novel functional associations between miRNAs and other biological entities Identify miRNAs that exert high influence on functional protein sets Define the role of miRNA context to modulate miRNA-mediated regulation Define principles that govern miRNA regulation of cellular network to orchestrate gene expression Build functional miRNA-target interactions by integrating indirect effect of miRNAs on target
-Identify miRNAs that exert high influence on cellular networks --Link miRNA systems biology with clinical data
--Utilize protein networks to better characterize the functional role of miRNAs
--Uncover the principles governing miRNA-mediated regulation and map them to miRNA function Research objectives: Network-based approaches for the functional characterization of miRNAs: a prostate cancer case study Applications of miRTI (1) Other applications for miRTI Coordinate miRNA regulation of functional protein sets Functional modulation between miRNAs miRNA decoys: Functional modulation between miRNAs and protein networks Network-based miRNA enrichment -I constructed functional miRNA-target interactions networks and proposed several applications (predict miRNA influence on cancer samples, predict novel associations between miRNAs and diseases, pathways, and miRNA enrichment)
-I proposed a method to characterize the coordinate miRNA regulation of functional protein sets
-I investigated the modulation effect of the protein partners of the target to modulate the expression of the target. I found that more than half of the protein in the signaling networks are regulated by miRNAs and modulated by the partners of the target.
-I proposed novel functional similarity measure between gene sets to assess the significance of the overlap. This is used as an enrichment analysis method that takes into account the importance of the overlapped genes in the biological networks Summary of contributions --Build more robust functional miRNA target interactions
--Generalize the network-based miRNA enrichment to other biological concepts
--Integrate TF-target networks Future work directions Publications More publications 1. M.Alshalalfa, M.Tan, G.Naji, R.Alhajj, F.Polat, and J.Rokne, Revealing miRNA regulation and miRNA target prediction using constraint-based learning, IEEE/Trans on Systems,Man,Cyber-C, 2012
2. M.Alshalalfa, L.Teng, L.Petersen, A.Bakkar, A.Almami, S.Liu, C.Brenner, M.Dolph, F.Feng, R.Alhajj, T.Bismar, Interrogation of ERG gene rearrangements in prostate cancer identifies prognostic novel signatures relative to disease progression, (submitted to Cancer Discovery)
3. Ashraf Bakkar, Mohamed Alshalalfa, Amal Al-Mami, Lars Petersen, Shuhong Liu, Samar hegazy, Tingting Wang, Samir Al-Bashir, Liang Hong Teng, Reda Alhajj, Moulay Alaoi-Jamail and Tarek A. Bismar, miR338-3p Exhibits a tumor suppressor role and inhibits invasion and metastasis in prostate cancer, (submitted to modern pathology)
4. M.Alshalalfa, R.Alhajj, Protein functional interactions modulate miRNA-protein associations, (submitted to Molecular BioSystems)
5. M.Alshalalfa, A.Alshekh, and R.Alhajj, Network-based miRNA functional enrichment, (Submitted to Bioinformatics)
6. M.Alshalalfa, G.Bader, T.Bismar, and R.Alhajj, Coordinate miRNA regulation of protein complexes in prostate cancer, (submitted PlosOne)
7. M.Alshalalfa, MicroRNA regulation in the context of functional protein networks (submitted to Molecular bioSystems) Principles governing miRNA regulation of protein networks Build functional miRNA-target interactions by integrating indirect effect of miRNAs on targets miRNA-target influence networks(miRTI): functional miRNA target interactions Prognostic significance of the high-influence miRNAs miRTI is effective to characterize miRNA effect on each sample Functional modulation between miRNAs Take-home message