Frequently Asked Questions

If your question is not here, please do not hesitate to contact us.

General questions

What is MetaDome?
MetaDome is a fast and easy-to-use web server that offers an easily accessible and unique perspective that enables researchers and clinicians to interpret variants of unknown significance via 'meta-domains'; a concept that we have previously validated ( L. Wiel et al. Human Mutation, 2017 ) which makes use of protein domain homology within the human genome to transfer genetic variant information across homologous domains. MetaDome can visualize meta-domain information and gene-wide profiles of genetic tolerance.
How can I use MetaDome?
Analyses through MetaDome can be performed by querying a gene name and desired transcript. The result is a visualization that a user may interact with to highlight positions of their interest and obtain more detailed information of those positions. This includes regional tolerance to missense variation and the presence or absence of variation at corresponding positions within homologous domains.

To get more familiar with the using MetaDome and all of it's functionality we strongly advise to start the tour.
Can I use my smartphone or tablet to access MetaDome?
Although we recommend using a laptop/desktop with a compatible browser for the best user experience, we designed the user interface to be useable for mobile devices as well. If you encounter any problems or see any possible improvements please contact us.
What desktop browsers are compatible for MetaDome?

The MetaDome web server is developed and extensively tested using Google Chrome and Firefox. We recommend using one of these browsers to access all functionality. Here is a list of compatible and tested browsers:

OS Version Chrome Firefox Microsoft Edge Microsoft IE Safari
Linux Ubuntu 16.04 and 18.04 70.0 63.0 n/a n/a n/a
MacOS Mojave 70.0 63.0 n/a n/a Not supported
Windows 7 and 10 70.0 63.0 Not tested Not supported n/a
I have ran into a problem with MetaDome, what can I do?
Although we have extensively tested MetaDome and are constantly monitoring the server for any downtime. If you do encounter problems or behaviour you did not expect. We would highly appreciate it if you could contact us.
On what data are the results in MetaDome based?
MetaDome combines data from various public resources. The underlying data of MetaDome currently contains information from 56,319 human transcripts (GENCODE), 71,419 Pfam protein domain instances, 12,164,292 population-based genetic variants from gnomAD, and 34,076 pathogenic mutations from ClinVar.
How often is the underlying data updated?
Currently MetaDome requires a manual reannotation of the underlying data. In a future version of MetaDome is expected to schedule automatic downloading of new data releases and automatic reannotation.
Is MetaDome still under construction?
MetaDome is final for its first release version. But we are still actively attempting to improve MetaDome based on feedback. If you have any improvement ideas, please contact us. Current improvements that we are working on may be found here.
Why can I not select my gene / transcript for analysis?
For sake of high data quality we have limited the possible transcripts and genes suitable for a MetaDome Analysis to the GENCODE Basic transcripts of which the translation is identically matched with a SwissProt protein sequence. All GENCODE Basic transcripts are validated to be expressed as mRNA and all SwissProt proteins are curated by experts.
I cannot find the domain that should be in my gene of interest?
All annotated protein domains in MetaDome result from Pfam. Pfam holds a strict notion on what a protein domain is and differs to other protein domain annotation services. We have specifically chose Pfam, as the underlying method is suitable to indicate homologously identical positions across protein domains that can directly be used to transfer variant information.

Interpretation of a MetaDome analysis

Why are there black boxes in the meta-domain landscape?
The black boxes represent positions that cannot be aligned to the Pfam domain consensus. For these positions we cannot transfer variant information across homologous domains.
How is the tolerance landscape computed?
The tolerance is computed as a from missense over synonymous variant count ratio, which is calculated in a sliding window manner to provide a per-position indication of regional tolerance to missense variation. The variants are based on gnomAD and corrected for codon composition. For more information we suggest reading "Computing genetic tolerance and generating a tolerance landscape".
What do the tolerance landscape' colours indicate?
The colours are based on missense over synonymous ratio computations over the entire protein for all proteins. Here the Yellow (or neutral) is based on the average missense over synonymous ratio score that you would obtain this way and the red (intolerant) and blue (tolerant) are based on the top/bottom scores.
For meta-domain information in the positional information, what does the alignment coverage mean?
This corresponds to how many homologous positions are aligned to that specific position. In general we would advise to maintain a minimum of 80% alignment coverage for high quality results.