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

[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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