N_xClinical

•  This view presents all the important information needed in evaluating an event together on a single screen to allow quick and confident interpretation of variants.

•  The layout automatically adjusts to the type of variant (e.g. CNV vs. Seq Var) as well as test type (Oncology vs. Constitutional)

Variant Details Tab - ConstitutionalSample - CNV Event:

Variant Details Tab - Oncology Sample - CNV Event:

Variant Details Tab - Constitutional Sample – Seq Var Event:

Variant Details Tab - Constitutional Sample – AOH Event:

• This feature automatically calculates the score for many of the evidence categories described by the ACMG technical standards for CNV interpretation. This new feature can also be coupled with N_xClinical's popular automated variant pre-classification decision tree to pre-classify events for both NGS and microarrays.
  
  For an in-depth description of the N_xClinical ACMG scoreboard read our blog: Hello, ACMG scoreboard. Goodbye, external calculator tools.
  

An industry first for isodisomy and heterodisomy with one-click Uniparental Disomy (UPD) detection, visualization, and reporting. When analyzing next-generation sequencing (NGS) or SNP-microarray data, N_xClinical users who deploy this new feature can now further investigate UPD events within duos and trios with one simple click - saving them valuable time during both the review process and tiered analysis.

For more detailed information on N_xClinical's one-click UPD detection check out our blog - Enhanced detection of UPD: there is more than the eye can see

Allow the laboratory to collect, organize, and use CNV, Seq Var, and AOH events from its own constitutional or oncology case history to create consistent interpretations and reports

• The KB supports two distinct types of applications - "Oncology" and "Constitutional" - each containing fields unique to the specified application type

• For Constitutional tests, the KB holds information such as relevant genes in the region, mode of inheritance, publication IDs and notes for each publication, interpretation texts, general comments, classification, etc. (see view below)

• For Oncology tests, the KB holds information such as classification based on the AMP guidelines, interpretation, notes, associated PubMed IDs, whether the event is diagnostic, prognostic, or therapeutic, etc.(see view below)

Constitutional Knowledgebase entry example:

Oncology Knowledgebase entry example:

•  Enable the creation of genome-wide CNV and AOH “profiles” in the knowledgebase with associated interpretation, publication links, and relevant gene content.

•  Compare a sample under review with all other profiles stored in the knowledgebase using unique genome-wide similarity metric to gauge similarity to other cancer types

Global Similarity function compares and ranks all saved profiles for CNV/AOH similarity against a sample under review

Global Similarity function compares a sample against all saved profiles to generate the following plot:

Interested in learning more?

Request a copy of our AMP 2020 poster titled "A Novel Machine Learning Approach to Characterize Cancer Signatures for Improved Clinical Reporting"

•Load your previous cases (yes, all of them) and compare them to your new ones.

•Automatically builds a case history of all samples analyzed and leverages this information in classification of new cases.

•BioDiscovery provides quarterly updates of annotations gathered and assembled from numerous databases such as OMIM (no charge), DECIPHER, ClinGen, DDG2P, CIViC, and more.

•Each site’s Admin decides when to deploy these updates across the lab so that each user is accessing the same database for consistency across the organization.

•Switch arrays, manufacturers or even  technology and still use the same software!

•NxClinical handles multiple platforms and technologies allowing a lab to continue using the same software as the lab’s testing arsenal evolves. Not only can multiple platforms be analyzed in the system, but the system can also derive multiple variant modalities from a single NGS assay.

•BioDiscovery’s CNV calling algorithms are the gold standard in the field for deriving CNVs from microarrays and NGS. BioDiscovery’s MSR algorithm makes it possible to obtain copy number from a variety of NGS data (WES, WGS, targeted panels, shallow sequencing).  This allows you to get the most out of a single NGS assay –  copy number, AOH, and sequence variants from the same assay streamlines the process and saves  time and money.

•NxClinical can be installed locally within a customer’s network or on the cloud. The highly scalable architecture allows the database to expand easily as a lab’s output grows without decreasing the speed of processing.

•Multiple processing units can be added and each indicated for a different type of data. E.g. a more powerful server may be used for WGS data while a less powerful server can quickly turn out array samples providing an efficient route to sample processing.

•The database also handles all types of platforms and technologies of various sizes from arrays and small panel NGS to WGS samples.

•NxClinical maintains all data in a single, centralized database that can be installed on the cloud or on-site within an institution’s own network. Multiple users can access the same data without causing inconsistencies and instant updates to the database allows all users to access the latest information immediately.

•The central database also houses information from external databases such as OMIM®, DECIPHER, CIViC, ClinGen providing the same reference and annotation data to all users accessing the system. Administrator defined protocol-based settings ensure processing consistency across samples of the same type.

•The centralized database provides efficient multi-user and remote access while ensuring consistency across different users and machines.  Assigned user roles and privileges ensure appropriate access and control of data. Notes and comments from different reviewers are tracked and instantly shared with colleagues. 

•Extensive audit trailing allows for traceability to meet potential regulatory demands.

•Automated workflows mirror a lab’s interpretation rules and/or regional guidelines (e.g. ACMG) providing a controlled environment adhering to reporting guidelines. Automated processes reduce errors often introduced by routine manual tasks.

•The Variant Interpretation Assistance (VIA) system incorporates lab classification rules to automatically pre-classify events. Machine learning approach uses classified events in automated case history review to classify new cases. Intelligent dynamic filtering minimizes false negative results and trims the list of potentially causative variants from thousands to a handful. Phenotype-driven variant prioritization (SAP scoring) using standardized vocabulary (HPO) quickly ranks clinically relevant events.

•The system includes other features that help adhere to such guidelines; e.g. confirmation of biological relationships for family-based analysis as recommended by ACMG guidelines. Enhanced filtering options include virtual gene panels to avoid detection of incidental findings and to segment a single test into multiple panels.

•Simultaneous review of seqvar, CNV, and AOH increases diagnostic yield. NxClinical is unique in that it stores both microarray and NGS data in the same database. Storing CNV and sequence variant data in a single database software system allows review and interpretation of all events (CNV, AOH, and sequence variants) simultaneously for a single sample.  This can help uncover synergistic events (e.g. a deletion of a recessive gene that also has a LOF mutation) which may not be easily revealed when using different software for each modality.

•Detection of compound events that may otherwise have been missed if analyzed via a test for a single modality increases diagnostic yield and saves time. It also enables easier management of tools with the need for only one analysis and interpretation tool and training on only one software system.

Case showing a compound event on TP53 – single base deletion (blue lollipop on browser at the top and indicated by purple arrows in the BAM reads track) and AOH (gold bar); plus the results table at the bottom.