CircRNAs in human and mouse tissues

by Hélène PerrinPosted on Leave a comment on CircRNAs in human and mouse tissues

Leng Han and Chunjiang He are the creators of the tissue-specific circular RNA (circRNA) database TSCD. They performed the first global analysis of tissue-specific cirRNAs and collected these data in a comprehensive database. Here, they talk about their work and how TSCD database could help researchers exploring their RNA sequencing data.

A repository of more than 300,000 tissue-specific RNAs

As circRNAs are attracting more attention in transcriptome research, we explored the global features of tissue-specific circRNAs in development and organ differentiation.

To identify tissue specific circRNAs, 3 algorithms, CIRI, circRNA_finder and find_circ, were applied on RNA-seq data collected from the ENCODE project and NCBI GEO database.

Based on the major types of circRNA, we identified more than 300,000 of tissue-specific circRNAs in different tissues. Our analysis indicated that tissue-specific circRNAs were mainly derived from exons, but may also be derived from introns or intergenic regions. The majority is generated from protein-coding genes, which suggested that these circRNAs may be associated to mRNA translation or be a backup of mRNA.

Among all circRNAs, 10.4% of human circRNAs and 34.3% of mouse circRNAs are tissue-specific, which suggested their association to tissue development. We also observed uneven distribution of tissue-specific circRNAs across different tissues. There are more tissue-specific circRNAs expressed in brain (89,137 were identified in fetal brain), and this might be owing to the complexity of neuronal activity in brain.

Abundance of TS circRNAs across different tissues:
16 adult human tissues (A), 15 fetal human tissues (B) and 9 mouse tissues (C) (in log2 of SRPTM: number of circular reads/number of mapped reads (units in trillion)/read length).

Functional enrichment analysis revealed that tissue-specific circRNAs are largely associated with tissue development and differentiation. To understand the potential functions of tissue-specific circRNAs, we identified a significant number of miRNA binding elements (MRE) and RBP (RNA binding protein) binding sites.

Finding a tissue-specific circRNA in TSCD

Users can easily browse TSCD content through browser page.
The users can view the tissue-specific circRNA by selecting :

  • Human adult or fetal tissue, or mouse
  • And one of the 26 individual tissues
    including adipose, adrenal, blood vessel, brain, esophagogastric, esophagus, eye, female gonad, heart, intestine, kidney, liver, lung, mammary gland, pancreas, skeletal muscle, skin, spleen, stomach, testis, thymus, thyroid gland, tibial nerve, tongue, umbilical cord, and uterus.

Data organization and visualization on TSCD web interface

All of the data were organized into a set of relational MySQL tables. Customized Java and PHP scripts were used to construct the interface of database. The visualization page displayed the coordinates of each circRNA.

The index page allows the user to easily query the information of TS circRNAs by chromosome, start and end site, junction read, conservation, genomic location, etc.

Web interface of TSCD

  1. The users can view the comprehensive information,
    as tissue category, circRNA ID, coordinates of backsplice sites, genomic locations, junction reads, strand information, genomic spanning length, gene annotation and MRE/RBP sites.
  2. More importantly, users can visualize the details of tissue-specific circRNA through the gene symbol link. Backsplices of circRNA are represented by arcs: black arc for the non-specific circRNAs, red arc for the tissue-specific circRNA.
  3. The annotated exons and introns of reference transcripts are displayed in the following panel. If the reference genes have multiple transcripts, all the transcripts are displayed. If the circRNA is generated from multiple genes, the exon structures of all related genes are displayed to better illustrate the biogenesis of circRNAs. TSCD provides the tables including all precise coordinates of each backsplice of circRNA across different tissues.

Exploring tissue-specific circRNAs with TSCD

TSCD provides several pages to benefit the research community:

1) The Browser-hg38|mm10 page which displayed coordinates for each circRNA based on the latest genome version, including GRCH38 and mm10.

2) Comparison page which allowed the users to compare circRNAs among different tissues.

3) Download page which allowed the users to batch download tissue-specific circRNAs from all tissues and the customized Perl script to identify the tissue-specific circRNAs from their own RNA-seq data.

References

(Xia et al., 2016) Comprehensive characterization of tissue-specific circular RNAs in the human and mouse genomes. Brief Bioinform.

Your Top 3 Circos plot generation tools

by Hélène PerrinPosted on Leave a comment on Your Top 3 Circos plot generation tools

Making great images of your data

With the growing amount of biological data generated, innovative bioinformatics tools have been developed for modelling and synthetizing complex information in comprehensive figures. Several infographics types are now available for an informative and clear representation and analysis of your data, and which differ depending on the specific domain and question you are studying.

So how do you choose the best tools to efficiently explore your data and illustrate your scientific findings?

To help you answer this key question, we have initiated a series of surveys with users on the main categories of data visualization tools among those which are most used by the OMICtools community. The first of our survey series concerns the Circos plot generation tools.

Using Circos plots

Circos plots allow you to visualize data in a circular layout. This kind of representation is particularly useful to integrate and compare large amounts of data. Circos is one of the best infographics to show relationships between elements. The Circos plot has become a standard method for presenting genomics and epigenomics data, genome annotation and comparative genomics, offering fine visualization of sequence alignments, conservation, synteny, rearrangements, gene expression, methylation levels, and more. Circos plots can also be used to display any kind of data domains with multi-layer features and relationships.

Here are the top 3 best tools, selected by 65 of you, OMICtools members, for creating Circos plots.

The Gold medal goes to the popular Circos tool

Your #1 top tool is the well-known command-line based Circos software, with 66% of the votes.

Originally conceived for visualizing genomic data such as alignments and structural variations, Circos uses a circular ideogram layout that can display data as a scatter, line or histogram plots, heat maps, tiles, connectors, and text.

Circos has features that makes it ideal for drawing genomic information. Shown here are ChIP-Seq, chr 22 methylation, whole-genome methylation, multi-species comparison, human genome variation and self-similarity and MLL recombinome.

Circos is a free command-line application written in Perl. It can be deployed on any operating system for which Perl is available (e.g. Windows, Mac OS X, Linux and other UNIX). Circos produces bitmap (PNG) and vector (SVG) images using plain text configuration and input files. A very complete website with documentation is available with a series of 8 online tutorials presenting each specific feature of Circos, a quick guide, support through the Circos forum, as well as several examples of published images.

For the last 10 years, this tool has helped thousands of scientists from various field to create beautiful representations of their data. Circos software has been used and referenced in more than 500 scientific publications and a larger variety of publications such as in the New York Times.

Silver medal for BioCircos.js and ggbio tools

The second place went to the BioCircos.js library and the R package ggbio, with 40% of the votes each.

Web visualization applications have the advantage of generating interactive graphs, in which all elements are interactive with mouse-over explanations and clickable buttons. This provides a more user-friendly Circos plot representation with easily accessible information.

BioCircos.js is an open source interactive JavaScript library, based on the D3 (Data-Driven Documents) and jQuery JavaScript libraries. It offers flexible plugins and powerful functionality for developers who need to build web-based applications for Circos plot generation. Biocircos.js supports multiple-platforms and works in all major internet browsers (Google Chrome is recommended). Biocircos.js version 1.1 is available (since September 2016), as well as updated documentation. Several modules are provided (SNP, CNV, HEATMAP, LINK, LINE, SCATTER, ARC, TEXT, and HISTGRAM) to display genome-wide genetic variations (SNPs, CNVs and chromosome rearrangement), gene expression and biomolecule interactions.

GGbio R package (version 1.24.1) offers the advantage of using the statistical functionality available in R as well as the grammar of graphics and the data handling capabilities of the Bioconductor project. A quick start guide and a manual were also released with Bioconductor. This tool has been mainly used to explore genome annotations and HTS data. The figures provide detailed views of genomic regions, sequence alignments and splicing patterns, and genome-wide overviews with karyogram, circular and grand linear layouts.

Ggbio application: Representation of copy number whole-genome profiles of five follicular lymphoma tumor samples generated from the Affymetrix Mapping 500K array. From Yin et al., 2012.  Genome Biology.

Bronze medal for the recent CircosVCF tool

The third place went to the web application CircosVCF with 34% of the votes.

CircosVCF is an interactive free web interface designed for vizualizing variants in genome-wide datasets. It was implemented in JavaScript and supports several browsers (Chrome, Firefox, Explorer 10+, Edge). CircosVCF provides circos visualization of input files in the standard Variant Call Format (large VCF files). It offers a very simplified user-friendly graphical interface to create Circos plots with an interactive design and the integration of additional information such as experimental data or annotations. The visualization capabilities of CircosVCF give a global overview of relationships between genomes and allow identification of SNPs regions.

Here is a demo for using CircosVCF:

 

Our next survey on data visualization will focus on heatmap generation tools. You are welcome to participate!

References

(Krzywinski et al., 2009) Circos: an information aesthetic for comparative genomics.  Genome Research.
(Cui et al., 2016) BioCircos.js: an interactive Circos JavaScript library for biological data visualization on web applications. Bioinformatics.
(Yin et al., 2012) ggbio: an R package for extending the grammar of graphics for genomic data.  Genome Biology.
(Drori et al., 2017) CircosVCF: circos visualization of whole-genome sequence variations stored in VCF files.  Bioinformatics.

3 tips to boost your OMICtools profile page

by Nicolas JacquetPosted on Leave a comment on 3 tips to boost your OMICtools profile page

After four years on the road (OMICtools was launched in 2013), it was time to make some changes to our user profile – and a new front-end version has now been implemented! You can customize your profile page quickly and easily, with each section of the profile page re-worked and re-designed to streamline what you want the community to know about you. 

Now’s the time to increase your visibility, and we can help you to succeed

At OMICtools we strive to offer you a better way to identify the right tools for your biomedical data. Today, we are working to make OMICtools the number #1 biomedical community platform, which also allows you to network with your peers, and speed up your scientific career.

When you register with us, a profile page is created and any activity you are involved in on OMICtools will be automatically displayed, highlighting your skills and expertise to establish your scientific reputation. So for example, if your add badges to credit your tasks relating to your tool development project, they will be directly acknowledged in your profile. Likewise, when you bookmark tools and put them into collections, your favorites will automatically appear on your profile and can be seen by other users.

Regardless of the social media platform you’re working with, presence and a personal touch are two keys to success. That’s pretty straightforward to do on Github, ResearchGate or Mendeley – and now it’s also easy to do on OMICtools – an entirely bioinformatics platform.

In short, the more customized your profile page, the greater the extent of your reach. Here are 3 tips to help you to stand out from the crowd.  

1. Complete your professional summary

Your description is the first thing visitors will see. If you want to draw people’s attention to your profile, create a strong presence. Not only will you be more easily seen but other users you interact with will show up in your discussion streams, which will make networking easier for everyone.

We suggest you add a profile picture and your full job title after your username to give yourself a clear brand. We also recommend your professional summary includes a description of what you do and gives an indication of why you’re on OMICtools. Make it easy for the reader – keep it short and direct.

Check out the profile settings located on the menu on the left side of your page to add more content. We recommend that you include:

  • your current position and where it is
  • your work experience and qualifications
  • your social profiles
A screenshot of an edited page

2. Share your work output

OMICtools is a great place to make your projects available openly. You can let your target audience know about your published work in the work experience section, along with a link to your article. Add your ORCID unique researcher identifier to distinguish yourself and your work from that of other researchers. If you don’t already have one, you can register for an ORCID and link it to your profile.

If you’ve participated in tool design, you can add a contributorship badge via the tool site and it will automatically appear in the bioinformatics projects section of your profile – if your tool isn’t already on OMICtools, submit it to the right category and then link it to your profile (and ask us if you need help submitting a tool!).

The list of badges allowing you to credit your expertise for specific tasks in software development (conceptualization, data curation, administration, testing, etc.).

3. Be active

A strong social media presence in the bioinformatics community can serve as an important foundation for your professional success! In June 2016, Kudos and the Altmetrics Research Team at the Centre for HEalthy and Sustainable CitieS (CHESS), and the Wee Kim Wee School of Communication and Information at Nanyang Technological University (NTU, Singapore) analyzed user data and found that 51% of registered Kudos users were STEM researchers sharing their work, 29% were social sciences researchers and 8% were humanities researchers. This demonstrates the engagement of STEM researchers, and how they are leading the way in using innovative tools to disseminate their research (from Williams et al., 2017. The new alchemy: Online networking, data sharing and research activity distribution tools for scientists. F1000Research).

  Being active on OMICtools is an easy way to reach your target audience. Open discussions in the tools’ forum to solve issues and be recognized as an expert in bioinformatics. Your comments will drive traffic to your profile and your tools.

Rating and reviewing tools is important. Leave relevant reviews on tools in your area of expertise. The bioinformatics audience is influenced by community feedback. The more reviews you post, the better your chances of ranking among the top contributors and appearing at the top of the experts list for your field.

An overview of the interactions you can see on a profile page

Thank you for your continuing support – we hope the new user profile release will contribute to making your experience on OMICtools easier and more effective, so check it out – just login and go to “Edit profile”!

Want to share your thoughts? Offer your feedback. Tell us if you’re satisfied and what you think can be improved.