1. VARIANT SPECIFIC ANNOTATIONS
AN ANNOTATIONS in GeneTalk is a user-generated content that is specific to a genomic position. It can contain
information about a genetic disorder or a link to a scientific article. Users can rate annotations in the category MEDICAL RELEVANCE and SCIENTIFIC EVIDENCE. Additionally users can provide comments to provide information or start
a discussion.
1.
2.
3.
Genomic position of the first nucleotide affected
Genotype or allele
Gene name and Entrez ID
4.
HGVS codes for DNA and protein level
5.
6.
7.
8.
9.
Author of annotation
Visibility to GeneTalk community
Annotation Text
Your rating for medical relevance and scientific evidence
User who provided a comment
Opens a new window at http://omim.org/
13. Link to publication in Pubmed
Opens the gene info viewer
Referring to the first affected letter in cDNA or protein
Contact user directly by clicking the mail button
10. Add your comment
11. Link to external source or website
12. OMIM-ID
Opens a new window at www.ncbi.nlm.nih.gov/pubmed/
14. Link to MutationTaster
Opens a new window at http://www.mutationtaster.org/ to
evaluates disease-causing potential of sequence alterations
15.
16.
17.
18.
19.
www.gene-talk.de
Star rating for medical relevance
Star rating for scientific evidence
Votes of all users
Click the VOTE button to apply your rating
Comment of a user

2. ANNOTATION RATING AND FILTERING
RATING OF ANNOTATIONS: The ratings in the category MEDICAL RELEVANCE range from one star (irrelevant or artifact) to five stars (disease
causing) and in the category SCIENTIFIC EVIDENCE from one star (very
low (e.g. incidental finding)) to five stars (very high (e.g. therapy studies)). Newly created annotations have to be rated by the user for medical relevance and scientific evidence. The initial rating of user counts as
three votes and every further rating as one.
Irrelevant or artifact
Suspicious
Disease associated
Disease modifying
Disease causing
Very low (e.g. incidental finding)
THE STAR RATING OF THE CATEGORIES medical relevance and scientific
evidence is based on the majority vote of the user community. Users
can adjust their rating at any time. The rating of the category changes as
soon as a new majority of users is found. The displayed star rating of an
annotation represents the majority of votes. All ratings are anonymous
but a vote counter shows the distribution of all ratings of the users.
GENETALK’S KOWLEDGEBASE: GeneTalk combined existing annotations from publicly available databases such as
HGMD, dbSNP and the 1000 genomes project
(1kGP). All annotations from the dbSNP that are flagged
as clinically precious and HGMD annotations that are
termed disease causing are initially rated with five stars
for medical relevance and scientific evidence. Technical
sequencing artifacts from the 1kGP blacklist were initially
rated with one star for medical relevance and five stars
for scientific evidence.
FILTER
VARIANTS BY MEDICAL RELEVANCE AND SCI-
ENTIFIC EVIDENCE:
You can set the annotation filter
to any level of medical relevance and scientific evidence. If the filter is set to two stars in medical
relevance for example all sequencing artifacts and
irrelevant variants will be removed. As a first approach in a diagnostic filtering procedure it might
be reasonable to start with a five star rating for
medical relevance and at least a two star rating for
scientific evidence. The total number of variants is
most effectively reduced when only variants with
annotations are kept. This setting can be used to
check whether there are variants in a data set
with already annotated mutation. If a patient cannot be diagnosed with this setting it is a more
complicated research question and other filtering
parameters have to be carefully chosen.
www.gene-talk.de
Low (e.g. multiple cases)
Medium (e.g. functional assays)
High (e.g. animal models)
Very high (e.g. therapy studies)