TRANSFAC

TRANSFAC

Content
Description	Transcription Factor Database
Data types captured	Eukaryotic transcription factors, their binding sites and binding profiles
Organisms	eukaryotes
Contact
Research center	Helmholtz Centre for Infection Research; BIOBASE GmbH
Primary citation	Wingender (2008)^[1]
Release date	1988
Access
Website	http://www.gene-regulation.com/pub/databases.html
Tools
Miscellaneous

TRANSFAC (TRANScription FACtor database) is a manually curated database of eukaryotic transcription factors, their genomic binding sites and DNA binding profiles. The contents of the database can be used to predict potential transcription factor binding sites.

1 Introduction
2 Content and Features
3 Availability
4 Applications
5 Similar Data Sources
6 References
7 External links

Introduction [edit]

The origin of the database was an early data collection published 1988.^[2] The first version that was released under the name TRANSFAC was developed at the former German National Research Centre for Biotechnology and designed for local installation (now: Helmholtz Centre for Infection Research).^[3] In one of the first publicly funded bioinformatics projects, launched in 1993, TRANSFAC developed into a resource that became available on the Internet.^[4]

In 1997, TRANSFAC was transferred to a newly established company, BIOBASE, in order to secure long-term financing of the database. Since then, the most up-to-date version has to be licensed, whereas older versions are free for non-commercial users.^[5]^[6]

Content and Features [edit]

The content of the database is organized in a way that it is centered around the interaction between transcription factors (TFs) and their DNA binding sites (TFBS). TFs are described with regard to their structural and functional features, extracted from the original scientific literature. They are classified to families, classes and superclasses according to the features of their DNA binding domains.^[7]^[8]^[9]^[10]

Binding of a TF to a genomic site is documented by specifying the localization of the site, its sequence and the experimental method applied. All sites that refer to one TF, or a group of closely related TFs, are aligned and used to construct a position-specific scoring matrix (PSSM), or count matrix. Many matrices of the TRANSFAC matrix library have been constructed by a team of curators, others were taken from scientific publications.

Availability [edit]

The usage of an older version of TRANSFAC is free of charge for non-profit users. Access to the most up-to-date version requires a license.

Applications [edit]

The TRANSFAC database can be used as an encyclopedia of eukaryotic transcription factors. The target sequences and the regulated genes can be listed for each TF, which can be used as benchmark for TFBS recognition tools or as training sets for new TFBS recognition algorithms.^[11] The TF classification enables to analyze such data sets with regard to the properties of the DNA-binding domains.^[12] Another application is to retrieve all TFs that regulate a given (set of) gene(s). In the context of systems-biological studies, the TF-target gene relations documented in TRANSFAC were used to construct and analyze transcription regulatory networks.^[13]^[14] By far the most frequent use of TRANSFAC is the computational prediction of potential transcription factor binding sites (TFBS). A number of algorithms exist which either use the individual binding sites or the matrix library for this purpose:

Patch – analyzes sequence similarities with the binding sites documented in TRANSFAC; it is provided along with the database.^[15]^[16]
SiteSeer – analyzes sequence similarities with the binding sites documented in TRANSFAC.^[17]^[18]
Match – identifies potential TFBS using the matrix library; it is provided along with the database.^[19]^[20]
TESS (Transcription Element Search System) – analyzes sequence similarities with binding sites of TRANSFAC as well as potential binding sites using the matrix libraries of TRANSFAC and three other sources.^[21]^[22] TESS also provides a program for the identification of cis-regulatory modules (CRMs, characteristic combinations of TFBSs), which uses TRANSFAC matrices.^[23]
PROMO – matrix-based prediction of TFBSs with aid of the commercial database version^[24]^[25]
TFM Explorer – Identification of common potential TFBSs in a set of genes^[26]^[27]
MotifMogul – matrix-based sequence analysis with a number of different algorithms^[28]
ConTra – matrix-based sequence analysis in conserved promoter regions^[29]^[30]
PMS (Poly Matrix Search) – matrix-based sequence analysis in conserved promoter regions ^[31]^[32]

Comparison of matrices with the matrix library of TRANSFAC and other sources:

T-Reg Comparator^[33] to compare individual or groups of matrices with those of TRANSFAC or other libraries.
MACO (Poly Matrix Search)^[34]^[35] – matrix comparison with matrix libraries.

A number of servers provide genomic annotations computed with the aid of TRANSFAC.^[36]^[37] Others have used such analyses to infer target gene sets.^[38]^[39]

Similar Data Sources [edit]

The following resources offer contents that are related to or partially overlapping with TRANSFAC:

JASPAR – collection of transcription factor binding profiles (matrices) and sequence analysis program
PLACE – cis-regulatory DNA elements in plants; until February 2007
PlantCARE – cis-regulatory elements and transcription factors in plants (2002)
PRODORIC – a similar concept as TRANSFAC for prokaryotes
RegulonDB – focus on the bacterium Escherichia coli
SCPD – specific collection of data- and tools for yeast (Saccharomyces cerevisiae) (1998)
TFe – the transcription factor encyclopedia
TRRD – Transcription Regulatory Regions Database, mainly about regulatory regions and TF-binding sites
PAZAR - Database with focus on experimentally validated transcription factor binding sites
HOCOMOCO - Homo Sapiens Comprehensive Model Collection ^[40]

References [edit]

^ Wingender, E. (2008). "The TRANSFAC project as an example of framework technology that supports the analysis of genomic regulation". Briefings in Bioinformatics 9 (4): 326–32. doi:10.1093/bib/bbn016. PMID 18436575.
^ Wingender, Edgar (1988). "Compilation of transcription regulating proteins". Nucleic Acids Research 16 (5): 1879–902. doi:10.1093/nar/16.5.1879. PMC 338188. PMID 3282223.
^ Wingender E, Heinemeyer T, Lincoln D (1991). "Regulatory DNA sequences: predictability of their function". Genome Analysis - from Sequence to Function; BioTechForum - Advances in Molecular Genetics (J. Collins, A.J. Driesel, eds.) 4: 95–108.
^ Wingender, E; Dietze, P; Karas, H; Knüppel, R (1996). "TRANSFAC: A database on transcription factors and their DNA binding sites". Nucleic Acids Research 24 (1): 238–41. doi:10.1093/nar/24.1.238. PMC 145586. PMID 8594589.
^ TRANSFAC Public on the gene regulation portal of BIOBASE
^ Access to TRANSFAC Public via TESS at the Computational Biology and Informatics Laboratory (CBIL) of University of Pennsylvania (Penn)
^ Wingender, E (1997). "Classification of eukaryotic transcription factors". Molekuliarnaia biologiia 31 (4): 584–600. PMID 9340487.
^ Heinemeyer, T; Chen, X; Karas, H; Kel, AE; Kel, OV; Liebich, I; Meinhardt, T; Reuter, I et al. (1999). "Expanding the TRANSFAC database towards an expert system of regulatory molecular mechanisms". Nucleic Acids Research 27 (1): 318–22. doi:10.1093/nar/27.1.318. PMC 148171. PMID 9847216. |displayauthors= suggested (help)
^ Stegmaier, P; Kel, AE; Wingender, E (2004). "Systematic DNA-binding domain classification of transcription factors". Genome informatics 15 (2): 276–86. PMID 15706513.
^ Wingender, E: The classification of transcription factors
^ Tompa, M., et al. (2005). "Assessing computational tools for the discovery of transcription factor binding sites". Nat. Biotechnol. 23 (1): 137–144. PMID 15637633. Text "doi:10.1038/nbt1053 " ignored (help)
^ Narlikar, L.; Gordan, R.; Ohler, U.; Hartemink, A. J. (2006). "Informative priors based on transcription factor structural class improve de novo motif discovery". Bioinformatics 22 (14): e384–92. doi:10.1093/bioinformatics/btl251. PMID 16873497.
^ Goemann, Björn; Wingender, Edgar; Potapov, Anatolij P (2009). "An approach to evaluate the topological significance of motifs and other patterns in regulatory networks". BMC Systems Biology 3: 53. doi:10.1186/1752-0509-3-53. PMC 2694767. PMID 19454001.
^ Kozhenkov, Sergey; Dubinina, Yulia; Sedova, Mayya; Gupta, Amarnath; Ponomarenko, Julia; Baitaluk, Michael (2010). "BiologicalNetworks 2.0 - an integrative view of genome biology data". BMC Bioinformatics 11: 610. doi:10.1186/1471-2105-11-610. PMC 3019228. PMID 21190573.
^ Patch on the free portal of BIOBASE
^ Matys, V. (2006). "TRANSFAC(R) and its module TRANSCompel(R): Transcriptional gene regulation in eukaryotes". Nucleic Acids Research 34 (90001): D108. doi:10.1093/nar/gkj143. PMC 1347505. PMID 16381825.
^ SiteSeer of the University of Manchester
^ Boardman, P. E.; Oliver, SG; Hubbard, SJ (2003). "SiteSeer: Visualisation and analysis of transcription factor binding sites in nucleotide sequences". Nucleic Acids Research 31 (13): 3572–5. doi:10.1093/nar/gkg511. PMC 168918. PMID 12824368.
^ Match on the free portal of BIOBASE
^ Kel, A.E.; Gössling, E; Reuter, I; Cheremushkin, E; Kel-Margoulis, OV; Wingender, E (2003). "MATCHTM: A tool for searching transcription factor binding sites in DNA sequences". Nucleic Acids Research 31 (13): 3576–9. doi:10.1093/nar/gkg585. PMC 169193. PMID 12824369.
^ TESS (Transcription Element Search System) at CBIL of the University of Pennsylvania
^ Site Search bei TESS
^ AnGEL CRM Searches in the TESS system
^ PROMO on the ALGGEN server of the Polytechnic University of Catalonia (UPC)
^ Messeguer, X.; Escudero, R.; Farre, D.; Nunez, O.; Martinez, J.; Alba, M.M. (2002). "PROMO: Detection of known transcription regulatory elements using species-tailored searches". Bioinformatics 18 (2): 333–4. doi:10.1093/bioinformatics/18.2.333. PMID 11847087.
^ TFM Explorer on the bioinformatics software server of the SEQUOIA group
^ Tonon, L.; Touzet, H.; Varre, J.-S. (2010). "TFM-Explorer: Mining cis-regulatory regions in genomes". Nucleic Acids Research 38 (Web Server issue): W286–92. doi:10.1093/nar/gkq473. PMC 2896114. PMID 20522509.
^ MotifMogul of the Institute for Systems Biology in Seattle
^ ConTra of the Ghent University
^ Hooghe, B.; Hulpiau, P.; Van Roy, F.; De Bleser, P. (2008). "ConTra: A promoter alignment analysis tool for identification of transcription factor binding sites across species". Nucleic Acids Research 36 (Web Server issue): W128–32. doi:10.1093/nar/gkn195. PMC 2447729. PMID 18453628.
^ PMS, developed at the Nanjing University
^ Su, G; Mao, B; Wang, J (2006). "A web server for transcription factor binding site prediction". Bioinformation 1 (5): 156–7. PMC 1891680. PMID 17597879.
^ T-Reg Comparator on the server of the Max Planck Institute for Molecular Genetics
^ MACO, developed at Nanjing University
^ Su, G; Mao, B; Wang, J (2006). "MACO: A gapped-alignment scoring tool for comparing transcription factor binding sites". In silico biology 6 (4): 307–10. PMID 16922693.
^ PReMOD: Human and mouse genome of the years 2004 & 2005; IRCM / McGill University, Montreal
^ PRIMA: Human genome of 2004; Tel-Aviv University
^ MSigDB: Mammalian transcription factor target gene sets; GSEA wiki server of Broad Institute of MIT and Harvard, Cambridge, MA
^ Xie, Xiaohui; Lu, Jun; Kulbokas, E. J.; Golub, Todd R.; Mootha, Vamsi; Lindblad-Toh, Kerstin; Lander, Eric S.; Kellis, Manolis (2005). "Systematic discovery of regulatory motifs in human promoters and 3′ UTRs by comparison of several mammals". Nature 434 (7031): 338–45. doi:10.1038/nature03441. PMC 2923337. PMID 15735639.
^ Kulakovskiy, Ivan V; Yulia A Medvedeva, Ulf Schaefer, Artem S Kasianov, Ilya E Vorontsov, Vladimir B Bajic, Vsevolod J Makeev (2013-01). "HOCOMOCO: a comprehensive collection of human transcription factor binding sites models". Nucleic acids research 41 (Database issue): D195–202. doi:10.1093/nar/gks1089. ISSN 1362-4962.