Try CSynth

CSynth is now available to try out yourself. Video walk-throughs are shown in the Media section. Your own data may be uploaded to CSynth by clicking on the “login / register” button below but be sure to try out the examples below first. If you have a connected HTC Vive headset, once the model is loaded clicking on the function key ‘F2’ will put CSynth into Virtual Reality mode allowing a completely new way to look at the data in 3D!

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Example 1. Comparison of the alpha-globin locus in different cell types:

CSynth has been used to model the mouse alpha globin locus using data from erythroid cells and embryonic stem (ES) cells. Matrices were generated from TriC data at 4kb resolution. This data is published in Nature Genetics (Oudelaar et al, 2018).

The figure above is a screenshot of CSynth with the two models loaded. (a) shows the menus that can be used to interact with the visualisation. (b) shows genes uploaded as BED format file for the region. Multiple BED files may be uploaded and switched between using the menu under the Modes or Annotations sections. (c) Visualisation of H3k4me1 data that has been uploaded in WIG format, is show as a widening of the diameter of the ribbon or chromatin backbone. The diameter of the ribbon may be adjusted interactively using the wigmult parameter in the Ribbon section of the menus. Similar to BED files multiple WIG format files may be uploaded and selected to view. (d) Using the mouse or VR pointer clicking any part of the heatmap shows a green intersecting line that represents the point selected  and the position is also shown as a corresponding point on the 3D model. This is useful when investigating patterns seen in the heatmap and their corresponding structures. (e) Shows the buttons that are generated when you upload more than one model. In this example two models have been uploaded allowing you to switch between the erythroid and embryonic stem cell models by selecting “erythroid cell IF” and “ES cell IF” respectively.

Example 1: Launch CSynth »


Example 2. Yeast, demonstration dataset (Crick model):

These data, derived from a study in fission yeast (S. pombe), shows conformational changes on the right arm of chromosome II during mitosis and interphase as well as the patterns of condensin binding sites. The data was modelled at the Crick Institute and is published in Nature Genetics (Kakui et al, 2017), and available at GEO (acc. GSE94478)
Files used in this dataset can be downloaded at: crick_data_files.zip

The data is from a high resolution experiment and may run slowly on some computers if they have integrated graphics card, rather than a discrete graphics card.

Example 2: Launch CSynth »


Example 3. Human structural variant on chromosome 13 in K562 cells compared with GM12878.

Using data from the Cell Paper (Rao et al. 2014)  “A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping” a structural variant is clearly visible when comparing between the two cell types on chromosome 13. CSynth gives some insight in how such structural variants physically would change the structure of chromatin. 

 

 

 

 

 

 

 

 

Example 3:  Launch CSynth »

Upload and model your own data:

To upload data you must be registered at CSynth:
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When uploading data to create a project the first dataset would be a file of experimentally-derived, contact information. This can be in either ‘.contacts’ format or ‘.normMatrix’ format (NOTE: upon upload, the latter format is converted to a binary equivalent, ‘.bintri’, format to improve CSynth performance). Video guides for uploading both data and annotations are available.

The following notes should be used to ensure any uploaded data is in a compatible format:

• Contacts Format: CSynth accepts a number of data formats. The contacts are recorded using a simple, 3-column file format, encoding the interaction between two positions on the chromosome (first 2 columns) and the strength of that interaction (last column). The expected file extension is ‘.contacts’. The contacts are restricted to cis interactions and each file should contain data relating to just one chromosome.
A typical example would look like:

• normMatrix Format: This matrix format enables whole genome contact data to be stored in relatively compact form.
Download an example dataset (zipped .normMatrix format)

• BED Format: The contacts file above is the minimum requirement for viewing data using CSynth and can be visualised without any further accessory files. It is sometimes useful however to highlight different regions of the genome under investigation using either text labels or by colouring the DNA backbone. Both of these can be achieved using an accessory, BED format identifying the regions to be highlighted.
This file records the name of the reference sequence, and the start  and end of the highlighted region in the first three columns. Any labels for the region are recorded in the fourth column and the desired colour (RGB value) for the region is recorded in the ninth column. An example of this file format is given below:

More details concerning BED format can be found at UCSC: file FAQ

• WIG Format:
This data format allows the visualisation of quantitative data (e.g. from ChIP-Seq) on the chromosome where the diameter of the ribbon increases proportionally to the value in the wig file.
More details concerning WIG format can be found at UCSC: file FAQ

• XYZ Format:
An existing conformational 3D model can be described using XYZ format and is useful to allow comparisons with the Hi-C contact data or the results of CSynth folding generated from Hi-C. An example of the XYZ file format is given below:

Data upload:
To upload data you must be registered at CSynth:
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