gnomAD annotated search

We've introduced an exciting new way to browse and filter variants using annotations provided by gnomAD for exomes. The existing search, which is based on the pipeline provided annotations, is unchanged and can still be used in the usual way. This format of the search looks at the same data, but viewed in a different way. There are several differences between 2 search mechanisms. The primary difference is that the pipeline annotated search is never updated and represents the annotations that were current at the time they were analyzed. On the other hand, the gnomAD annotated search is updated quarterly with every new release of gnomAD across all previously analyzed patients. By using the latest frequencies and gene names, we can go back and review cases that were previously unsolved. There are several other differences that should be noted: The pipeline annotated search displays ONE variant linked to ONE transcript. With the gnomAD annotated search, we are displaying transcripts (not variants), which means for one variant we can have MULTIPLE transcripts. The significance of this is that in the search results, we may see multiple rows for the same variant, represented by different transcripts. The other difference, are the tabbed search results. The pipeline annotated search currently shows a single tab for all search results. With gnomAD annotated search, we are splitting the results into 2 tabs. The first tab displays variants that have a link to a gnomAD record. The second tabs lists variants that have no link to gnomAD. By default, the gnomAD annotated search assumes the assembly build is GRCh38. If users need to go back and look at previously analyzed patients, they should remember to switch the assembly to GRCh37. Some new filters were introduced including: LoF (loss of function), Homozygous count, Canonical, and gnomAD consequence. It should be noted that structural variants are not supported in the gnomAD annotated search. To search SVs, please continue to use the pipeline annotated search. The new gnomAD search is not meant to replace the pipeline search, but to complement it with fresh new information for the variants gnomAD has coverage for which has far lower coverage than the pipeline. It is highly recommended to use both. For a demonstration video please follow this link: https://youtu.be/iGRiP8hmet8

Comments

Post a Comment

Popular posts from this blog

Measuring Variant Conservation with GERP Score and Siphy

The more annotations, the better! We've recently added 2 new annotations to assist with variant prioritisation as a measure of variant conservation and these are GERP scores and Siphy. GERP stands for Genomic Evolutionary Rate Profiling. Conceptually, GERP is a method for the identification of slowly evolving regions in a multiple sequence alignment, defined as ‘constrained elements’. "Constrained elements are identified by comparing the observed to the expected rates of evolution for each window, and defining all those regions whose collective observed rates of evolution are significantly lower than would be expected under a null model." More simply, it is a score used to calculate the conservation of each nucleotide in multi-species alignment with ranges from -12.3 to 6.17, with 6.17 being the most conserved. Positive scores (observed fewer than expected) indicate that a site is under evolutionary constraint. Negative scores may be weak evidence of accelerated rates of
Read more

Custom Exomiser reports

Users can now run Exomiser using parameters of their choosing. For example, users can set the allele frequency , variant type, inheritance mode, and model organisms. To use Exomiser, from the menu Reports -> Exomiser. Results will be emailed to you when completed.
Read more

Supplementary information available for download

As part of our datasets for download, we've added some supplementary information (generated as TXT files by the pipeline) to go along with the VCFs and BAMs files. The files contain information such as the cutoffs used to qualify variants as a PASS, which include things like read depth cutoffs, median quality score cutoffs and so on. Furthermore, the files also contain general statistics about total variants passed, the proportion of variants that are exonic, splice sites, number of distinct genes and averages of read depth and median quality. Another file called the 'readReport.summary' includes information about how many were paired, mispaired, aligned, and unaligned. The supplemantary files can be found under the 'Datasets' section.
Read more