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BY m.ghorbani
MiRNA in computational
biologyThe Nobel Prize in Physiology or Medicine for 2006 Andrew Z. Fire and Craig C. Mellofor their discovery of "RNA interference – gene silencing by double-stranded RNA"
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contentsIntroduction miRNA
Computational identification of miRNA
Computational identification of target miRNA
miRNA database
Boahong zhang ,xiaoping pan , 2006. computational identification of miroRNA
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Introduction miRNAMicroRNA are one class of newly
identified riboregulators of gene expression in many eukaryotic
organism.
Mature miRNA have 20-24 nucleotides
Boahong zhang ,xiaoping pan , 2006. computational identification of miroRNA
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Tasks of miRNAThey play important roles in multiple
biological and metabolic processes , including
Developmental timingSignal transductionDifferentiationCell fate identityDiseases and carcinogenesis
Boahong zhang ,xiaoping pan , 2006. computational identification of miroRNA
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Coordinated action of miRNA nodes in developmental timing and tailoring leaf shape
www.cs.ucf.edu/~shzhang/CAP5510/lec14.ppt
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Produce mature miRNAMature miRNA formation requires a
multiple –step process.I. miRNA gene is first transcribed to a
primary miRNA by Pol II enzymeII. Cleaved to a stem loop intermediate
termed pre-miRNA by DroshaIII. Pre-miRNAs are further cleaved to
miRNA: miRNA* duplex IV. Mature miRNA are releaseed for
regulating targeted gene expressionBoahong zhang ,xiaoping pan , 2006. computational identification of miroRNA
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Major characterstics of microRNAsHairpin-shaped secondary structures
High conservation for some miRNA
High minimal folding free energy index
Boahong zhang ,xiaoping pan , 2006. computational identification of miroRNA
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History identification of miRNAmiRNAS were initially identified by a
genetic screening technology
Recently , direct cloning of miRNAs , followed by small RNA isolation
Computational approaches
Boahong zhang ,xiaoping pan , 2006. computational identification of miroRNA
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Computational approachesThe principles of computational approaches
are base on
I. Hairpin-shaped stem loop secondary structure
II. High evolutionary conservation
III. High minimal folding free energy index
Boahong zhang ,xiaoping pan , 2006. computational identification of miroRNA
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classificationThe computational approaches can be
classified into five major categoriesI. Homology search-basedII. Gene searchIII. Neighbor stem loop searchIV. Algorithms based on comparative
genomicsV. Phylogentic shadowing-based
Boahong zhang ,xiaoping pan , 2006. computational identification of miroRNA
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Homology search-based approachIdentifying miRNA genes by searching
nucleotide database using BLOST programIt was well recognized that miRNA are
evolutionarily conservedProfile-based search programs , such asI. ERPINII. miAlign
Boahong zhang ,xiaoping pan , 2006. computational identification of miroRNA
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Classification of homology s..I. GENOME-BASE SEARCH
II. ESTS-BASE SEARCH
Partial cDNA sequences of expressed gened cloned into a plasmid
A powerfull approach to identify miRNA genes in species whose genome sequence are not available
Boahong zhang ,xiaoping pan , 2006. computational identification of miroRNA
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GENE-FINDING APPROACHGene-finding approaches are designed for
predicting animal miRNA
Not depend on homology or miRNA conservation
Boahong zhang ,xiaoping pan , 2006. computational identification of miroRNA
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How gene-finding workI. First need to identify conserved genomic
regions
II. These regions into a window 110-n
III. Using a specific computer program
Boahong zhang ,xiaoping pan , 2006. computational identification of miroRNA
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How program workWindow is folded with secondary structure
program such as mfold or RNA fold
hairpin-shaped stem loops for potential miRNA candidates
Boahong zhang ,xiaoping pan , 2006. computational identification of miroRNA
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Computer programs homology search basedMiRseeker analyzing conserved sequences that adopt
an extended stem loop secondary structure
Accuracy 75% for Drosophila miRNAmiRscanIdentify miRNA base on common
characteristics (such as base pairing and nucleotide bias )
Boahong zhang ,xiaoping pan , 2006. computational identification of miroRNA
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MiRscan
Scan to find conserve hairpin structures
Using known miRNA genes at training set
Yong Huang. The discovery approaches and detection methods of microRNAs
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Processes of MiRscanI. A 110-nt window along both strand
II. Folding the window with RNAfold
III. A folding free energy of as a least -25 kcal/mol
IV. Passing a 21-nt window along each stem-loop
V. Assigning a log likelihood score to each position for its similarity to know miRNA
Yong Huang. The discovery approaches and detection methods of microRNAs
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Computational identification of microRNA TARGETS
A high degree of complementarity to the miRNAs
This allows the prediction of miRNA targets by computational approaches
Boahong zhang ,xiaoping pan , 2006. computational identification of miroRNA
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Computational approaches are based onMiRNA are perfectly or near perfectly
complementary to their target miRNA
The RNA-RNA duplex has a higher negative folding free energy
Binding sites of mRNA and miRNA is highly conserved
Boahong zhang ,xiaoping pan , 2006. computational identification of miroRNA
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programsFind miRNA
Mir check
Target scan
MiRanda
Boahong zhang ,xiaoping pan , 2006. computational identification of miroRNA
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miRNA databasemiR Base
ASRP
miRna AMap
Boahong zhang ,xiaoping pan , 2006. computational identification of miroRNA
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