Identification of putative miR direct targets by microarray data
Ovarian Serous Cystadenocarcinoma (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/C1N29W6H
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-29b MLLT11 -0.461 miranda,pictar,targetscan 1 1 1 3
hsa-mir-29b TDG -0.432 miranda,pictar,targetscan 1 1 1 3
hsa-mir-29a TDG -0.425 miranda,pictar,targetscan 1 1 1 3
hsa-mir-29a MYBL2 -0.419 miranda,pictar,targetscan 1 1 1 3
hsa-mir-29b MFAP2 -0.416 miranda,pictar,targetscan 1 1 1 3
hsa-mir-29a DNMT3B -0.403 miranda,pictar,targetscan 1 1 1 3
hsa-mir-29b VASH2 -0.401 miranda,pictar,targetscan 1 1 1 3
hsa-mir-29a MLLT11 -0.400 miranda,pictar,targetscan 1 1 1 3
hsa-mir-29b DNMT3A -0.387 miranda,pictar,targetscan 1 1 1 3
hsa-mir-29b DNMT3B -0.385 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-29b 20 BLMH, COL2A1, COL4A2, COL4A5, DNMT3A, DNMT3B, EIF4E2, FAM130A1, GPX7, JARID2, MFAP2, MLLT11, MYBL2, TDG, TRIM37, TUBB, TUBB2A, TUBB2B, VASH2,FSTL1
hsa-mir-29a 13 BLMH, DNMT3A, DNMT3B, GPX7, JARID2, MFAP2, MLLT11, MYBL2, TDG, TRIM37, TUBB, VASH2,EIF4E2
hsa-mir-29c 8 DNMT3A, EIF4E2, GPX7, MFAP2, MLLT11, TUBB2B, VASH2,FSTL1
hsa-mir-9 2 LMNA,KCTD12
hsa-mir-26b 1 TMEM2
hsa-mir-183 1 MEF2C
hsa-mir-142-3p 1 HMGA2
hsa-mir-182 1 MMD
hsa-mir-30b 1 ECOP
hsa-mir-200c 1 ZEB1
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
EIF4E2 3 hsa-mir-29b, hsa-mir-29c,hsa-mir-29a
MFAP2 3 hsa-mir-29b, hsa-mir-29c,hsa-mir-29a
GPX7 3 hsa-mir-29b, hsa-mir-29c,hsa-mir-29a
VASH2 3 hsa-mir-29b, hsa-mir-29c,hsa-mir-29a
MLLT11 3 hsa-mir-29b, hsa-mir-29c,hsa-mir-29a
DNMT3A 3 hsa-mir-29b, hsa-mir-29c,hsa-mir-29a
FSTL1 2 hsa-mir-29c,hsa-mir-29b
MMD 2 hsa-mir-30c,hsa-mir-182
DNMT3B 2 hsa-mir-29b,hsa-mir-29a
JARID2 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/OV-TP/19078536/GDAC_MergeDataFiles_12185920/OV-TP.mirna__h_mirna_8x15kv2__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/OV-TP/19078556/GDAC_MergeDataFiles_12185944/OV-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)