MiRNA in computational biology 1 The Nobel Prize in Physiology or Medicine for 2006 Andrew Z. Fire and Craig C. Mello for their discovery of "RNA interference.

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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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Dedicated to all mothers

in the world

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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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How microRNA regulates the target mRNA genes

www.cs.ucf.edu/~shzhang/CAP5510/lec14.ppt

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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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Program online

http://bioinforma.weebly.com/mirna-prediction.html

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MiRscan

http://bioinforma.weebly.com/mirna-prediction.html

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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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THANK YOU

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