Identification of putative miR direct targets by microarray data
Overview
Introduction

This pipeline infers putative direct gene targets of miRs based on miR and gene expression profiles across multiple samples.

Summary

This pipeline use a relevance network approach to infer putative miR:mRNA regulatory connections. All miR:mRNA pairs that have correlations < -0.3 and have predicted interactions in three sequence prediction databases (Miranda, Pictar, Targetscan) define the final network.

Results
Significant miR:gene pairs

Figure 1.  Get High-res Image All miR hubs with their strong anti-correlated genes and predicted interactions in three sequence prediction databases.

Table 1.  Get Full Table List of miR:gene pairs with corr < -0.30 and predicted interactions in three sequence prediction databases.

miR gene Corr prediction databases miranda pictar targetscan total
hsa-mir-22 CHD7 -0.497 miranda,pictar,targetscan 1 1 1 3
hsa-mir-34a SOX4 -0.471 miranda,pictar,targetscan 1 1 1 3
hsa-mir-27a FAM77C -0.465 miranda,pictar,targetscan 1 1 1 3
hsa-mir-23a PAK3 -0.441 miranda,pictar,targetscan 1 1 1 3
hsa-mir-9 FBN1 -0.430 miranda,pictar,targetscan 1 1 1 3
hsa-mir-152 CHD7 -0.429 miranda,pictar,targetscan 1 1 1 3
hsa-mir-34a DPYSL4 -0.429 miranda,pictar,targetscan 1 1 1 3
hsa-mir-27a CDK5R1 -0.424 miranda,pictar,targetscan 1 1 1 3
hsa-mir-9 P4HA2 -0.418 miranda,pictar,targetscan 1 1 1 3
hsa-mir-9 TGFBI -0.414 miranda,pictar,targetscan 1 1 1 3
miR connections

Table 2.  Get Full Table All miR hubs with their associated genes in the putative direct target network.

Mir Number.of.Genes Genes
hsa-mir-29a 21 ARVCF, BACH2, BCL11A, BLMH, DNMT3A, DNMT3B, EPHB3, HMGCS1, JARID1B, KCTD15, MYBL2, NASP, REV3L, RNF138, SOX12, SS18L1, TDG, TUBB, VASH2, ZBTB5,SETDB1
hsa-mir-9 17 ANXA2, CAPZA1, CAST, COL15A1, DSE, FBN1, GPR124, LDLRAP1, LEPRE1, P4HA2, RAI14, SHC1, SLC10A3, SLC25A24, TGFBI, TXNDC5,SDC2
hsa-mir-27a 13 AMOTL2, CA10, CABP1, CDK5R1, CHD7, EYA1, FAM77C, FRS3, PASK, PLCL2, RNF144A, SLCO5A1,RPS6KA5
hsa-mir-22 10 CHD7, CUL3, DGKI, H3F3A, JARID2, POGK, RSBN1, SNRK, SPEN,SEPHS1
hsa-mir-29b 10 BACH2, BLMH, DNMT3A, DNMT3B, JARID1B, MYBL2, TDG, TUBB, VASH2,NASP
hsa-mir-23a 9 B3GALT2, CDK5R1, CHD7, DNM3, MTSS1, PAK3, PKP4, SATB1,CAMTA1
hsa-mir-34a 7 E2F3, HN1, PDGFRA, SATB1, SOX4, TAF5,DPYSL4
hsa-mir-29c 5 BLMH, JARID1B, MYBL2, TUBB,BACH2
hsa-mir-155 4 CHD7, SATB1, ZNF238,CAMTA1
hsa-mir-222 4 POGZ, RIMS3, SHANK2,RP11-35N6.1
Gene connections

Table 3.  Get Full Table All gene hubs with their associated miRs in the putative direct target network.

Gene Number.of.Mirs Mirs
CHD7 5 hsa-mir-155, hsa-mir-22, hsa-mir-23a, hsa-mir-27a,hsa-mir-152
BLMH 3 hsa-mir-29b, hsa-mir-29c,hsa-mir-29a
TUBB 3 hsa-mir-29b, hsa-mir-29c,hsa-mir-29a
CDK5R1 3 hsa-mir-23a, hsa-mir-27a,hsa-mir-152
MYBL2 3 hsa-mir-29b, hsa-mir-29c,hsa-mir-29a
JARID1B 3 hsa-mir-29b, hsa-mir-29c,hsa-mir-29a
SATB1 3 hsa-mir-23a, hsa-mir-34a,hsa-mir-155
BACH2 3 hsa-mir-29b, hsa-mir-29c,hsa-mir-29a
TDG 2 hsa-mir-29b,hsa-mir-29a
NASP 2 hsa-mir-29b,hsa-mir-29a
Methods & Data
Input

This section should list the files that were used as input.

  • Level 3 miR expression file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/GDAC_MergeDataFilesPipeline/GBMLGG-TP/19076868/GDAC_MergeDataFiles_12184404/GBMLGG-TP.mirna__h_mirna_8x15k__unc_edu__Level_3__unc_DWD_Batch_adjusted__data.data.txt

  • Level 3 gene expression file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/GDAC_MergeDataFilesPipeline/GBMLGG-TP/19076891/GDAC_MergeDataFiles_12184409/GBMLGG-TP.transcriptome__ht_hg_u133a__broad_mit_edu__Level_3__gene_rma__data.data.txt

  • miR:gene predicted interactions file = /xchip/cga/reference/miR_predictions/human_interactions.predicted.v2.txt

  • Miranda = microrna.org Aug 2010 release, Microcosm version 5

  • Pictar = version 1

  • Targetscan = release 5.2

Pearson corelation

Pairwise Pearson correlations coefficients between all miR:gene pairs are first computed. All genes that have correlation values less than the user-defined threshold (-0.3) with a particular miR and have been predicted as targets of that miR in three sequence based prediction databases: Miranda[1][2] Pictar[3][4], TargetScan [5][6][7] are identified as putative direct targets of that miR. We infer a direct target miR:gene network which comprises all such putative direct associations.

  • threshold = -0.3

References
[1] Betel D, Wilson M, Gabow A, Marks DS, Sander C, microRNA target predictions: The microRNA.org resource: targets and expression, Nucleic Acids Res 36:D149-53 (2008)
[2] John B, Enright AJ, Aravin A, Tuschl T, Sander C, Marks DS, miRanda: Human MicroRNA targets., PLoS Biol 3(7):e264 (2005)
[3] Krek A, Grun D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, MacMenamin P, Piedade ID, Gunsalus KC, Stoffel M, Rajewsky N, Combinatorial microRNA target predictions, Nature Genetics 37:495-500 (2005)
[4] Chen K, Rajewsky N, Natural selection on human microRNA binding sites inferred from SNP data., Nat Genet 38:1452-1456 (2006)
[5] Lewis BP, Burge CB, Bartel DP, Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are MicroRNA Targets., Cell 120(120):15-20 (2005)
[6] Grimson A, Farh KK, Johnston WK, Garrett-Engele P, Lim LP, Bartel DP, MicroRNA Targeting Specificity in Mammals: Determinants beyond Seed Pairing., Molecular Cell 27:91-105 (2007)
[7] Friedman RC, Farh KK, Burge CB, Bartel DP, Most Mammalian mRNAs Are Conserved Targets of MicroRNAs., Genome Research 19:92-105 (2009)
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