Introducing Geneyx Analysis Release version 5.17

Key highlights

1. Runs of Homozygosity (ROH): Mapping ROH events to the CNV/SV genetic model provides insight into consanguinity and autosomal recessive disorder risk, enhancing whole genome sample analysis.

2. OMIM Clinical Synopsis: Integration of clinical synopsis from OMIM database aids in understanding the link between genetic variations and clinical phenotypes, improving clinical interpretation.

3. AlphaMissense: Addition of AlphaMissense predictive model offers pathogenicity scores for single nucleotide missense variants, aiding in clinical interpretation.

4. In-House Structural Variant Annotation: Updates to CNV/SV variant columns enhance identification of causal mutations and noise filtering.

5. Improved QC Data Metrics: Additional output metrics improve quality control assessment, aiding in sample quality determination.

6. Annotate Dark and Camouflage Genes: Integration of Dark and Camouflage gene annotations enhances CNV analysis accuracy and comprehensiveness.

7. Enhanced Audit Trails: Granular documentation of modifications in Analysis History provides detailed insights into sample analytical trajectory.

8. Introducing Secondary Sample Mode: Introduction of a Mode field allows seamless activation of somatic or germline pipeline, enhancing transparency in the analysis process.

New Features

Runs of Homozygosity (ROH): ROH refers to a stretch of consecutive homozygous genetic markers on both chromosomes, which can be indicative of offspring from consanguineous marriages and increase the risk of autosomal recessive disorders. ROH events are now mapped to the CNV/SV genetic model and will be displayed by default if using the Geneyx DRAGEN Secondary pipeline for whole genome samples. Alternatively, ROH events can be imported using the unification script here: https://github.com/geneyx/geneyx.analysis.api/tree/main/scripts/UnifyVcf.

Distance from Splice Sites: Analyzing the distance of each variant from the splice site can serve as an important method for filtering. Geneyx now supports the distance of the splice site to the canonical splice site location and provides the ability to filter on this column, now displayed in Genomic and Genetic Data column.

OMIM Clinical Synopsis: The Clinical Synopsis section in the Online Mendelian Inheritance in Man (OMIM) database offers concise gene-specific summaries of clinical features and symptoms associated with genetic disorder/syndrome, along with information about the molecular basis of the associated disease. The Clinical Synopsis from OMIM is now supported when clicking on the Gene name in Geneyx Analysis aimed to be a valuable resource for users aiding in the understanding of the link between genetic variations and clinical phenotypes.

AlphaMissense: AlphaMissense (published here PMID: 37733863) is a predictive model that generates pathogenicity scores for single nucleotide missense variants in human protein-coding genes. The predictions cover a vast number of possible variants (71 million) across approximately 19,000 genes. The pathogenicity scores provided by AlphaMissense range from 0 to 1 and can be interpreted as the predicted probability of a variant being clinically pathogenic. Higher scores suggest a higher likelihood of the variant contributing to a clinical condition. This annotation can be seen in the Effect&Prediction column.

Improvements

In-House Structural Variant Annotation: The In-House CNV/SV variant column has been updated with new information for events that have been identified in previous samples. This includes associated quality scores, classifications, interpretations, phenotypes and more. This will serve to better enhance identifying causal mutations and filter out CNV/SV associated with background noise. Matching events will be based on 80% similarity.

Improved QC Data Metrics: Users that start from the secondary pipeline in Geneyx will now obtain additional output metrics that pertain to the quality control of the data. This information will be viewed in the audit trail of the secondary, and in the analysis screen when clicking on the VCF level information. This will give users useful sample information to easily determine the quality of the sample.

Annotate Dark and Camouflage Genes: Dark and camouflage genes refer to those that are difficult to pinpoint due to various reasons, such as their location in genomic regions with complex structural variations, repetitive sequences, or areas prone to technical challenges in sequencing. Annotating Dark and Camouflage genes helps to improve the accuracy and comprehensiveness of CNV analysis. As such Dark (low sequencing depth) and Camouflage (ambiguous alignment) are now new columns integrated into the CNV/SV tab and displayed in IGV.  

Updates

Enhanced Ethnicity MAF Filtering: Recognizing the distinct variation frequencies within diverse human populations, Geneyx acknowledges that a uniform approach may not be suitable for all. Consequently, we have reintroduced the functionality to filter based on Minor Allele Frequencies (MAF) specific to individual sub-populations. This reinstated feature empowers users to fine-tune filtering strategies, catering to the nuanced genetic landscapes of various ethnicities, thereby optimizing precision in genomic analyses. This information is available when expanding the FREQUENCY category of a variant analysis.

Enhanced Audit Trails: Ensuring transparency throughout the various stages of a sample’s journey is crucial for comprehending alterations as it transitions between different users within your organization. The upgraded granularity of the Analysis History, accessible through the Analysis Details window, meticulously documents any modifications made to a specific case, providing a more detailed and insightful overview of the sample’s analytical trajectory. This improvement fosters a clearer understanding of the actions undertaken at each step in the analysis process.

Introducing Secondary Sample Mode: Formerly, the initiation of either the somatic or germline pipeline was contingent upon the selected sample source. Now, a novel field called “Mode” has been introduced, encompassing the options of Somatic and Germline. By choosing the appropriate mode, users can seamlessly activate the corresponding pipeline, bringing a heightened level of transparency to the process and offering a distinct delineation of the pipeline set to commence.

Geneyx’s latest release, version 5.17, incorporates updated data sources, enhancing the platform’s capabilities and ensuring access to the most current genetic information. The update includes refreshed data from reputable databases such as UCSC, Omim, ClinVar, ClinGen, LitVar2, MANE (now updated to version 1.3), and Civic.

Get in touch with our sales and distributor for details on this version release

We believe that these updates will not only streamline your genomic analyses but also contribute to more insightful and accurate results. Our commitment to staying at the forefront of genomics is reflected in the improved data sources, refined filtering options, and upgraded audit trails, all aimed at enhancing your overall experience.

As we continue to innovate and refine our platform, your feedback remains invaluable. We encourage you to explore the new features and functionalities and reach out to our support team for any queries or assistance. Your insights drive our ongoing efforts to deliver cutting-edge solutions for genetic analysis.

In addition, we are excited to announce our participation in the ESHG Conference in Berlin, Germany. If you are attending, we invite you to visit our booth to engage with our team, explore live demos, and discuss how #Geneyx can further support your genomics research and analysis needs. We look forward to connecting with you at the conference and continuing our collective journey toward advancing genomic insights.

Thank you for choosing Geneyx.