TFM-Explorer

Examples of use for TFM-Explorer


Muscle dataset

The muscle dataset was initially introduced by Wasserman and Fickket (Wasserman and Fickket, 1998) and is often used in the literature to assess the accuracy of cis-regulatory modules prediction tools. It is also presented in the general assessment paper (Klepper et al.,2008). We use this latter source, and retrieved RefSeq accession numbers when available. This results in a set of 19 genes from human, mouse, rat and chicken.

This example illustrates that the method is able to identify large or short regions, and that some transcription factors have a preferred location in regards of the Transcription Start Site.

TFM-Explorer parameters

Default parameters were used.

RefSeq numbers

> mouse
#Mus musculus cholinergic receptor, nicotinic, alpha polypeptide 1
NM_007389
# Mus musculus troponin C, cardiac/slow skeletal (Tnnc1), mRNA
NM_009393
#Mus musculus cholinergic receptor, nicotinic, beta polypeptide 1 (muscle) (Chrnb1), mRNA. 
NM_009601
#Mus musculus cholinergic receptor, nicotinic, gamma polypeptide (Chrng), mRNA.
NM_009604
# Mus musculus actin, alpha 1, skeletal muscle (Acta1), mRNA.
NM_009606
#Mus musculus myosin, heavy polypeptide 6, cardiac muscle, alpha (Myh6), transcript variant 2, mRNA.
NM_010856
#Mus musculus myosin, light polypeptide 4 (Myl4), mRNA.
NM_010858
#Mus musculus myogenin (Myog), mRNA.
NM_031189
> human
#Homo sapiens actin, alpha 1, skeletal muscle (ACTA1), mRNA.
NM_001100
#Homo sapiens desmin (DES), mRNA.
NM_001927
# Homo sapiens myosin, heavy chain 6, cardiac muscle, alpha (MYH6), mRNA.
NM_002471
#Homo sapiens myogenin (myogenic factor 4) (MYOG), mRNA.
NM_002479
#Homo sapiens troponin I type 1 (skeletal, slow) (TNNI1), mRNA.
NM_003281
#Homo sapiens actin, alpha, cardiac muscle 1 (ACTC1), mRNA.
NM_005159
> chicken
#Gallus gallus troponin T type 2 (cardiac) (TNNT2), mRNA.
NM_205449
> rat
#Rattus norvegicus cholinergic receptor, nicotinic, beta 1 (muscle) (Chrnb1), mRNA.
NM_012528
#Rattus norvegicus myogenic factor 6 (Myf6), mRNA.
NM_013172
#Rattus norvegicus myosin, heavy chain 6, cardiac muscle, alpha (Myh6), mRNA.
NM_017239
#Rattus norvegicus actin, alpha 1, skeletal muscle (Acta1), mRNA.
NM_019212
  

Skin dataset

The second dataset is concerned with genes preferentially expressed in skin tissues, available from the TiGER database (Liu et al.,2008). It is made of 27 human sequences.

This example illustrates how TFM-Explorer can help to distinguish between modules involving transcription factors that could cooperate and spurious modules coming from matrices whose occurrences overlap intrinsically.

TFM-Explorer parameters

The location range has been set to -5000bp:0bp and TRANSFAC vertebrate matrices were used.

RefSeq numbers

> skin dataset
#Homo sapiens gap junction protein, beta 1, 32kDa (GJB1), transcript variant 2, mRNA.
NM_000166
#Homo sapiens microphthalmia-associated transcription factor (MITF), transcript variant 4, mRNA.
NM_000248
#Homo sapiens plasminogen activator, tissue (PLAT), transcript variant 1, mRNA.
NM_000930
#Homo sapiens NCK adaptor protein 2 (NCK2), transcript variant 2, mRNA.
NM_001004720
#Homo sapiens NCK adaptor protein 2 (NCK2), transcript variant 3, mRNA.
NM_001004722
#Homo sapiens deoxyribonuclease I-like 2 (DNASE1L2), mRNA.
NM_001374
#Homo sapiens chondroitin sulfate proteoglycan 4 (CSPG4), mRNA.
NM_001897
#Homo sapiens transient receptor potential cation channel, subfamily M, member 1 (TRPM1), mRNA.
NM_002420
#Homo sapiens neuronal PAS domain protein 1 (NPAS1), mRNA.
NM_002517
#Homo sapiens thyroid hormone responsive (SPOT14 homolog, rat) (THRSP), mRNA.
NM_003251
#Homo sapiens tumor necrosis factor receptor superfamily, 
#member 14 (herpesvirus entry mediator) (TNFRSF14), mRNA.
NM_003820
#Homo sapiens isocitrate dehydrogenase 3 (NAD+) alpha (IDH3A),
# nuclear gene encoding mitochondrial protein, mRNA.
NM_005530
#Homo sapiens keratin 16 (KRT16), mRNA.
NM_005557
#Homo sapiens antigen p97 (melanoma associated) identified by monoclonal antibodies 133.2 and 96.5 (MFI2), 
#transcript variant 1, mRNA.
NM_005929
#Homo sapiens phosphomevalonate kinase (PMVK), mRNA.
NM_006556
#Homo sapiens nuclear receptor subfamily 4, group A, member 3 (NR4A3), transcript variant 1, mRNA.
NM_006981
#Homo sapiens protein interacting with PRKCA 1 (PICK1), transcript variant 1, mRNA.
NM_012407
#Homo sapiens glyceraldehyde-3-phosphate dehydrogenase, spermatogenic (GAPDHS), mRNA.
NM_014364
#Homo sapiens lymphocyte antigen 6 complex, locus K (LY6K), transcript variant 1, mRNA.
NM_017527
#Homo sapiens F-box protein 6 (FBXO6), mRNA.
NM_018438
#Homo sapiens leucine rich repeat and fibronectin type III domain containing 3 (LRFN3), mRNA.
NM_024509
#Homo sapiens family with sequence similarity 167, member B (FAM167B), mRNA.
NM_032648
#Homo sapiens chromosome 6 open reading frame 114 (C6orf114), mRNA.
NM_033069
#Homo sapiens family with sequence similarity 46, member B (FAM46B), mRNA.
NM_052943
#Homo sapiens ENTH domain containing 1 (ENTHD1), mRNA.
NM_152512
#Homo sapiens calpain 3, (p94) (CAPN3), transcript variant 4, mRNA.
NM_173088
#Homo sapiens abhydrolase domain containing 12B (ABHD12B), transcript variant 2, mRNA.
NM_181533

Presynaptic dataset

The third dataset contains genes with high expression in brain tissues and low levels of expression in other tissues, taken from (Liu et al.,2009). The authors selected nine presynaptic genes that show strong neuronal expression.

This example illustrates that the pairwise correlation calculus between clusters may reveal significant correlations between some of the computed clusters.

TFM-Explorer parameters

The location range has been set to -1500bp:0bp, the P-value to 0.00, the ratio to 4 and TRANSFAC vertebrate matrices were used.

RefSeq numbers

> presynaptic dataset
#Homo sapiens calcium/calmodulin-dependent protein kinase II inhibitor 1 (CAMK2N1), mRNA.
NM_018584
#Homo sapiens dynamin 1 (DNM1), transcript variant 1, mRNA.
NM_004408
#Homo sapiens RAB3A, member RAS oncogene family (RAB3A), mRNA.
NM_002866
#Homo sapiens RAB3C, member RAS oncogene family (RAB3C), mRNA.
NM_138453
#Homo sapiens secretory carrier membrane protein 5 (SCAMP5), mRNA.
NM_138967
#Homo sapiens synaptosomal-associated protein, 25kDa (SNAP25), transcript variant 1, mRNA.
NM_003081
#Homo sapiens syntaxin binding protein 1 (STXBP1), transcript variant 2, mRNA.
NM_001032221
#Homo sapiens synaptic vesicle glycoprotein 2A (SV2A), mRNA.
NM_014849
#Homo sapiens synapsin I (SYN1), transcript variant Ia, mRNA.
NM_006950

References

X. Liu, X. Yu, D. J Zack, H. Zhu, and J. Qian. Tiger: A database for tissue-specific gene expression and regulation. BMC Bioinformatics, 9(271), 2008. [doi: doi:10.1186/1471-2105-9-271 ] [PubMed Central: PMC2438328 ] [PubMed: PMID:18541026 ].
K. Klepper, G. K. Sandve, O. Abul, J. Johansen, and F. Drablos. Assessment of composite motif discovery methods. BMC Bioinformatics, 9(123), 2008. [PubMed: PMID:18302777 ] [PubMed Central: PMC2311304 ] [doi: doi:10.1186/1471-2105-9-123 ].
W. W. Wasserman and J. W. Fickett. Identification of regulatory regions which confer muscle-specific gene expression. Journal of Molecular Biology, 278(1), 1998. [PubMed: PMID:9571041 ] Central: ] [doi: doi:10.1006/jmbi.1998.1700 ].
R. Liu, S. Hannenhalli, and M. Bucan. Motifs and cis-regulatory modules mediating the expression of genes co-expressed in presynaptic neurons. Genome Biology, 10(R72), 2009. [PubMed: PMID:19570198 ] [PubMed Central: PMC2728526 ] [doi: doi:10.1186/gb-2009-10-7-r72 ].