Tag Archives: CircuitsDB

Tip of the Week: A year in tips III (last half of 2010)

As you may know, we’ve been doing tips-of-the-week for three years now. We have completed around 150 little tidbit introductions to various resources. At the end of the year we’ve established a sort of holiday tradition: we are doing a summary post to collect them all. If you have missed any of them it’s a great way to have a quick look at what might be useful to your work.

Here are the tips from the first half of the year, and below you will find the tips from the last half of 2010 (you can see past years’ tips here: 2008 I2008 II2009 I2009 II):

July

July 7: Mint for Protein Interactions, an introduction to MINT to study protein-protein interactions
July 14: Introduction to Changes to NCBI’s Protein Database, as it states :D
July 21: 1000 Genome Project Browser, 1000 Genomes project has pilot data out, this is the browser.
July 28: R Genetics at Galaxy, the Galaxy analysis and workflow tool added R genetics analysis tools.

August

August 4: YeastMine, SGD adds an InterMine capability to their database search.
August 11: Gaggle Genome Browser, a tool to allow for the visualization of genomic data, part of the “gaggle components”
August 18: Brenda, comprehensive enzyme information.
August 25: Mouse Genomic Pathology, unlike other tips, this is not a video but rather a detailed introduction to a new website.

September

September 1: Galaxy Pages, and introduction to the new community documentation and sharing capability at Galaxy.
September 8: Varitas. A Plaid Database. A resource that integrates human variation data such as SNPs and CNVs.
September 15: CircuitsDB for TF/miRNA/gene regulation networks.
September 21: Pathcase for pathway data.
September 29: Comparative Toxicogenomics Database (CTD), VennViewer. A new tool to create Venn diagrams to compare associated datasets for genes, diseases or chemicals.

October

October 6: BioExtract Server, a server that allows researcher to store data, analyze data and create workflows of data.
October 13: NCBI Epigenomics, “Beyond the Genome” NCBI’s site for information and data on epigenetics.
October 20: Comparing Microbial Databases including IMG, UCSC Microbial and Archeal browsers, CMR and others.
October 27: iTOL, interactive tree of life

November

November 3: VISTA Enhancer Browser explore possible regulatory elements with comparative genomics
November 10: Getting canonical gene info from the UCSC Browser. Need one gene version to ‘rule them all’?
November 17: ENCODE Data in the UCSC Genome Browser, an entire 35 minute tutorial on the ENCODE project.
November 24: FLink. A tool that links items in one NCBI database to another in a meaningful and weighted manner.

December

December 1: PhylomeDB. A database of gene phylogenies of many species.
December 8: BioGPS for expression data and more.
December 15: RepTar, a database of miRNA target sites.

Tip of the Week: CircuitsDB for TF/miRNA/gene Regulation Networks


In this week’s tip I’d like to introduce you to CircuitsDB, which describes itself as:

“…a database where transcriptional and post-transcriptional (miRNA mediated) network information is fused together in order to propose and recognize non trivial regulatory combinations. “

I found out about the database from the BioMed Central article “CircuitsDB: a database of mixed microRNA/transcription factor feed-forward regulatory circuits in human and mouse“, which I cite below. I had already been thinking about miRNAs because I am slated to update our miRBase tutorial in the near future and have been reading/catching up on the latest in the field. The CircuitsDB paper by Olivier Friard et al does a really nice job of quickly and clearly laying out the background of the project – how transcription factors have long been studied for their transcriptional regulation of protein-coding genes involved in any manor of pathways, including those of disease. It goes on to describe that the study of microRNAs, or miRNAs, is a newer field studying the post-translational regulatory effects of miRNAs on protein-coding genes and their functions. Current efforts are moving to integrate the two areas of research to create more complete, and admittedly more complex, regulatory views of protein-coding genes and the affects on disease and other pathways.

The developers of CircuitsDB also very clearly describe how they have mined, analyzed and connected data from several top databases – many of which we have tutorials on, such as OMIM, miRBase, Ensembl and others – in order to create feed-forward regulatory loops, or FFLs, of TFs, affected miRNAs and ultimately affected protein-encoding genes. The image at the right is from their original paper: “Genome-wide survey of microRNA–transcription factor feed-forward regulatory circuits in human” (cited below), which reported the development of the computational framework for the mixed miRNA/TF Feed-Forward regulatory circuits that are freely available through the  CircuitsDB web interface. This original paper is available for free, with registration to RSC Publishing, and provides a detailed description of their original development, as well as access to several supplemental files.

Essentially networks linking transcription factors and affected genes, miRNAs and affected genes, and transcription factors and miRNAs were painstakingly connected through an ab-initio oligo analysis. Support was then gained for the connections by analyzing enriched GO terms, disease connections, and previously-known connections found in other specialized resources. The CircuitsDB interface offers multiple tools. The main tool (FFL) is what I show in this tip & is the tool that searches for the networks diagrammed above. The MYC FFL is an impressive “curated database of miRNA mediated Feed Forward Loops involving MYC as Master Regulator”, and includes information on the direction of regulation, loop participants, evidence levels and more. The Transcriptional network tool allows a user to search with either a miRNA & find its regulating TF, or search with a TF & find regulated genes or miRNAs. The Post-transcriptional network tool is similar, but allows searches for a miRNA or gene to find regulated genes or regulating miRNA, respectively. So check out the tip & then check out CircuitsDB – enjoy!

References:
Friard, O., Re, A., Taverna, D., De Bortoli, M., & Corá, D. (2010). CircuitsDB: a database of mixed microRNA/transcription factor feed-forward regulatory circuits in human and mouse BMC Bioinformatics, 11 (1) DOI: 10.1186/1471-2105-11-435

Re, A., Corá, D., Taverna, D., & Caselle, M. (2009). Genome-wide survey of microRNA–transcription factor feed-forward regulatory circuits in human Molecular BioSystems, 5 (8) DOI: 10.1039/B900177H