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MiRaGE: Inference of gene expression 
regulation via microRNA transfection II


 Y­h. Taguchi/Dept.Phys.,Chuo Univ.
Jun Yasuda /School Med.,Tohoku Uinv.
MiRaGE:

MiRNA Ranking by Gene Expression

What is miRNA?

non­coding RNAs which bind to mRNAs 
and cleavage  them or disturb translation. 
Regulation of gene expression via miRNA

       Computer oriented  prediction 
                        (uncertain)
   Target genes genome



    microRNA               mRNA

    microRNA               mRNA         3
miRNA target gene list 




                     Gene8
                     Gene7
                     Gene6
                     Gene5
                     Gene4
                     Gene3
                     Gene2
                     Gene1
simple seed match
(Virtual)
               miRNA1 ○×○○○○××
               miRNA2 ○×○○××○○
Prediction     miRNA3 ×○○×○○××
               miRNA4 ○○○×○○××
                    VS

                    Human lung cancer
 gene1
 gene2
                 miRNA1
                         Real
 gene3
                                        4
Concepts of MiRaGE method
          Control        Treated 
All of
miRNAs'                              Gene 
target                               Expression
    Gather the information of miRNAs' targets

  Compare the expressions of targets for each 
  miRNAs and check significance (see Next Slides)

       Calculate False Discovery Rate
                                                5

      Generate ranking  of each miRNA
Computation of significance

       miRNA   Targets         Down        P­value        FDR
       miR­a              54           3            0.5           0.4
1st    miR­b          120             54         0.0001         0.005
       miR­c              36           1            0.5           0.7
       ...     ...             ...         ...            ...

2nd    miR­X              60          18          0.001         0.007



      Reject miR­a & c because the FDR > 0.05


                     Ranking                                            6
 Application
Inference of transfection of miRNA to human 
lung cancer cell
Gene expression by
Array: Agilent
at
One and three days 
after transfection of
Mir­107, mir­185, and let­7a.

log(xg[miRNA]) vs log(xg[Control])
               xg: gene expression

Target gene list: simple seed match 

ICIC2011, LNBI in press. (2011/8/11­14)
Transfected miRNA
               mir­107     mir­185      let­7a
time replicate 1 replicate 2 replicate 1 replicate 2 replicate 1 replicate 2
day1 1[1st] 1[1st] 7[1st] 9[1st] 2[1st] 2[1st]
day3 1[1st] 0[­­­] 0[1st] 0[­­­] 1[1st] 1[1st]
Numbers of significant miRNAs. 
The ranks of transfected micriRNAs are shown in 
square brackets.

  Transfected miRNAs are 
  correctly identified by MiRaGE 
  method.
Conclusion

MiRaGE method can correctly infer 
regulation of miRNA vis target mRNA 
expression.
The application is now planed...
Web Server

http://granular.com/MiRaGE/
 now available

Data base
http://granular.com/MiRaGEDB/
Collection of results by MiRaGE to GEO
(Gene expression Omnibus)
coming soon...
 

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