miRNA Target Prediction

1. miRNA collection

    miRNAs used in our database are collected from several miRNA expression publications. In detail, we categorized them as schizophrenia related miRNAs, brain expressed miRNAs and non-brain expressed miRNAs respectively. For the schizophrenia related miRNAs, two independent studies have identified 18 miRNAs differently expressed in brain cortex of schizophrenia patients compared with control samples using microarrary (16 from Perkins et al. 2007 and 2 from Beveridge et al. 2008). We collected all of them and denoted as SZ miRNAs in our database. For brain expressed miRNAs, we studied miRNA microarray expression data and several miRNA regulation survey papers( Burmistrova et al. 2007; Beveridge et al. 2008; Zhang and Su 2008). After removing the SZ miRNAs we have identified before, we got 87 brain expressed miRNAs and denoted them as brain miRNAs in our database. Finally, we collected the miRNAs expressed in non-brain tissues from two large-scale miRNA expression atlas studies ( Landgraf et al. 2007; Liang et al. 2007). After removing the miRNAs which have been classified as SZ or brain miRNAs before, we got the list of non-brain expressed miRNAs.

2. miRNA Target Prediction

    We used the TargetScan (Version 4.2) to predict miRNA targets in our constructed schizophrenia candidate genes. TargetScan defines the positions from 2 to 7 of a mature miRNA as its seed sequence and use this seed sequence to perform prediction. Since miRNA families are comprised of miRNAs with the same seed sequences, the target sites on a gene are identical in term of miRNA families. For miRNAs conserved in mammals or vertebrates, we restrict that the predicted target sites being conservative across species. For non-conserve miRNAs in mammals, we used both conserved and non-conserved predicted target sites, so the resulted target sites will be much more than those predicted by conserved miRNAs.

    The miRNA seed match types of TargetScan are 1A, m8 or both of them.

  • 1A: 7mer-1A, An exact match to positions 2-7 of the mature miRNA (the seed) followed by an 'A'
  • m8: 7mer-m8, An exact match to positions 2-8 of the mature miRNA (the seed + position 8)
  • 1A, m8: An exact match to positions 2-8 of the mature miRNA (the seed + position 8) followed by an 'A'
  • Beveridge, N.J., Tooney, P.A., Carroll, A.P., Gardiner, E., Bowden, N., Scott, R.J., Tran, N., Dedova, I., and Cairns, M.J. 2008. Dysregulation of miRNA 181b in the temporal cortex in schizophrenia. Hum Mol Genet 17: 1156-1168 PubMed
  • Burmistrova, O.A., Goltsov, A.Y., Abramova, L.I., Kaleda, V.G., Orlova, V.A., and Rogaev, E.I. 2007. MicroRNA in schizophrenia: genetic and expression analysis of miR-130b (22q11). Biochemistry (Mosc) 72: 578-582 PubMed
  • Landgraf, P., Rusu, M., Sheridan, R., Sewer, A., Iovino, N., Aravin, A., Pfeffer, S., Rice, A., Kamphorst, A.O., Landthaler, M., et al. 2007. A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 129: 1401-1414 PubMed
  • Liang, Y., Ridzon, D., Wong, L., and Chen, C. 2007. Characterization of microRNA expression profiles in normal human tissues. BMC Genomics 8: 166. PubMed
  • Perkins, D.O., Jeffries, C.D., Jarskog, L.F., Thomson, J.M., Woods, K., Newman, M.A., Parker, J.S., Jin, J., and Hammond, S.M. 2007. microRNA expression in the prefrontal cortex of individuals with schizophrenia and schizoaffective disorder. Genome Biol. 8: R27. PubMed
  • Zhang, R. and Su, B. 2008. MicroRNA regulation and the variability of human cortical gene expression. Nucleic Acids Res 36: 4621-4628. PubMed

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