Glioblastoma Multiforme: Identification of putative miR direct targets
Maintained by Sachet Shukla (Broad Institute)
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
Overlap of miR:gene network with sequence prediction databases

Figure 1. Get High-res Image Distribution of miR:gene pairs by the number of sequence prediction databases that predict an interaction between the two molecules. Miranda, Targetscan and Pictar are the three databases used in the analysis. Only miR:gene pairs that have correlation values less than the threshold are shown.

miR connectivity distribution

Figure 2. Get High-res Image Summary of miR counts by the number of associated genes in the putative direct target network

Gene connectivity distribution

Figure 3. Get High-res Image Summary of gene counts by the number of associated miRs in the putative direct target network

Significant miR:gene edges

Table 1. Get Full Table List of miR:gene pairs with corr < -0.30 and prediction support in Miranda, Targetscan and Pictar

miR | gene | corr | prediction databases | miranda | pictar | targetscan | total
--- | --- | --- | --- | --- | --- | --- | ---
hsa-mir-22 | CHD7 | -0.5 | miranda,pictar,targetscan | 1 | 1 | 1 | 3
hsa-mir-27a | FAM77C | -0.47 | miranda,pictar,targetscan | 1 | 1 | 1 | 3
hsa-mir-34a | SOX4 | -0.47 | miranda,pictar,targetscan | 1 | 1 | 1 | 3
hsa-mir-152 | CHD7 | -0.45 | miranda,pictar,targetscan | 1 | 1 | 1 | 3
hsa-mir-9 | P4HA2 | -0.44 | miranda,pictar,targetscan | 1 | 1 | 1 | 3
hsa-mir-23a | PAK3 | -0.44 | miranda,pictar,targetscan | 1 | 1 | 1 | 3
hsa-mir-9 | FBN1 | -0.44 | miranda,pictar,targetscan | 1 | 1 | 1 | 3
hsa-mir-9 | TGFBI | -0.44 | miranda,pictar,targetscan | 1 | 1 | 1 | 3
hsa-mir-27a | CDK5R1 | -0.43 | miranda,pictar,targetscan | 1 | 1 | 1 | 3
hsa-mir-29a | MYBL2 | -0.42 | 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 | 23 | ARVCF, BACH2, BCL11A, BLMH, DNMT3A, DNMT3B, EPHB3, HMGCS1, JARID1B, KCTD15, MYBL2, NASP, PCGF3, PRR3, 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 | 14 | AMOTL2, CA10, CABP1, CDK5R1, CHD7, EYA1, FAM77C, FRS3, PASK, PLCL2, RNF144A, SLCO5A1, ZNF238,RPS6KA5
hsa-mir-23a | 10 | B3GALT2, CDK5R1, CHD7, DNM3, MTSS1, PAK3, PKP4, SATB1, ZNF238,CAMTA1
hsa-mir-22 | 10 | CHD7, CUL3, DGKI, H3F3A, JARID2, POGK, RSBN1, SNRK, SPEN,SEPHS1
hsa-mir-29b | 10 | BACH2, BLMH, DNMT3B, EPHB3, JARID1B, MYBL2, TDG, TUBB, VASH2,NASP
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
ZNF238 | 3 | hsa-mir-23a, hsa-mir-27a,hsa-mir-155
BACH2 | 3 | hsa-mir-29b, hsa-mir-29c,hsa-mir-29a
TDG | 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/GBM/1668939/2.GDAC_MergeDataFiles.Finished/GBM.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/GBM/1668895/2.GDAC_MergeDataFiles.Finished/GBM.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

Method

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

This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.

- Analysis Results (MD5 checksum)

- Auxiliary Data (MD5 checksum)

- MAGE-TAB File (MD5 checksum)

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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