An Important  Advancement in Genome Sequencing: Version 5.15

1. APIs: https://github.com/geneyx/geneyx.analysis.api/wiki  

Get Sample File URL:  

• Geneyx now supports the ability to download the BAM, BAI, and QcMetrics files for a given sample that was processed from the secondary implemented within Geneyx. This API will provide a URL that will enable download of the requested file*.  

Get Coverage for Gene Panel:

• Geneyx now supports the ability to download the full coverage profile for a given sample that was processed from the secondary pipeline using a specified gene panel. The file output will be in JSON format, and will include standard coverage outputs as well as the MANE Select transcript ID.  
• *QC metrics can also be downloaded using the GUI at the VCF Sample level for those processed using a secondary in Geneyx.  

Get Sample Metrics File URL:

• Geneyx now supports the ability to download the full QcMetrics files of a given sample that was processed from the secondary implemented within Geneyx. This API will provide a zipped TSV file with qc and mapping metrics.   
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2. IGV Genome Browse Visualization

The genome browser (IGV), used for variant visualization, is now updated within the Geneyx platform. This includes:  

1. New window for IGV: Now when a variant is selected for visualization by clicking on the location, IGV will display in a new window. This will allow for visualization to occur on a different monitor and can be easily referenced using the URL.  
2. Color coordinated ClinVar variants: Geneyx now provides color coordinates for the ClinVar SNV track. This enables a visual understanding based on classification for the variant of interest and neighboring variants.  
3. Ability to Customize Layout: Geneyx now supports the ability to customize the default tracks in IGV through the settings.  
4. Plotting variant track: In IGV, SNV and SV from the proband and associated samples derived from the VCF are displayed as a new track. This will allow the exact variant to be investigated.  
   

3. LitVar2

LitVar2 allows the search of variant specific information from relevant studies in literature. It is now an integrated annotation source that will enhance phenotypic prioritization through improved literature mining and can be used for retrieving variant-level publications.  

4. Variant Tags

Variant tags are now integrated when annotating variants. Default variant tags include de-novo, somatic, founder mutation, and more, and they can be configured in the Settings screen.

Updated information: Epigenetics: Impact, Resources, and Technology in DNA Methylation Analysis by Eli Sward 

Improvements:  

➡ Repeat Expansions:

a. Split Column View: Repeat expansions, which can be viewed in the CNV/SV genetic model, are now split into two columns. The first will show the observed copies on allele one and allele two, and the second column will show the repeat unit. Hovering over the repeat will show the reference allele copy. We also incorporated a color-coding scheme to distinguish between reference, pre-mutation and mutations ranges.  

b. Ability to import Repeat files: Geneyx now supports the ability to import repeats from different file formats, including DRAGEN, ONT, and PacBio.  

c. Local Variant Count: For every repeat observed, a local variant count is created based on the same copies present across all internal samples. Clicking on the LV column will also display a histogram plot with these sample counts and associated data in which the repeat has been observed.

➡ ACMG Guidelines  

a. PP3: If a variant is associated with a High severity logic, PP3 will automatically be applied. With this logic, the severity outcome will follow the impact expectations.  

b. PS2: If a trio workflow is implemented, PS2 will activate when both parents are healthy and do not carry the variant, and the same variant of the proband is observed with a phenotypic prioritization or is present in OMIM.  

c. PM2: This criterion now uses the allele number from gnomAD to apply PM2. For PM2 to activate the allele number must be higher than 0 but smaller or equal to 2000.  

d. BS2: For autosomal recessive and X-linked genes, BS2 will be activated if there are 5 homozygous or hemizygous variants in gnomAD exomes or genomes. For autosomal dominant genes, BS2 will activate if there are three homozygous or 15 heterozygous in gnomAD exomes or genomes.  

d. Start Loss variants: will now automatically activate PM4 instead of PVS1. 

➡ Pseudogenes  

a. A new pseudogene database is now used to correctly identify all genes that are located in pseudogene region.  

Beyond these exciting new features, we are excited to announce our upcoming participation in the ASHG 2023 conference in Washington, DC, November 1st-5th. 

If you plan to attend, please let us know, and we will be delighted to meet with you. Our booth number for this conference is 200. At this conference, we plan to show how Geneyx is advancing long read sequencing technologies as a novel tertiary analysis solution.

Thank you for your continued support and valuable feedback that drives the evolution of Geneyx Analysis. We look forward to assisting you further in your genomic research endeavors.

If you have any additional features or suggestions you would like to see implemented, please don’t hesitate to reach out to our dedicated support team at support@geneyx.com.

* * Of note, massive BAM files downloads might be subjected to fees associated with bandwidth consumption.