Identification of putative miR direct targets by microarray data
Glioma (Primary solid tumor)
21 August 2015  |  analyses__2015_08_21
Maintainer Information
Citation Information
Maintained by Sachet Shukla (Broad Institute)
Cite as Broad Institute TCGA Genome Data Analysis Center (2015): Identification of putative miR direct targets by microarray data. Broad Institute of MIT and Harvard. doi:10.7908/C1RF5T7B
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

Download Results

In addition to the links below, the full results of the analysis summarized in this report can also be downloaded programmatically using firehose_get, or interactively from either the Broad GDAC website or TCGA Data Coordination Center Portal.

References
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[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)