Cartagenia n.v. Announces the Release of Its BENCH lab NGS Solution for Clinical NGS Data Analysis

The new product is tailored to support the adoption of Next Generation Sequencing technology in routine clinical practice and focuses on standardizing the data interpretation process.

Key challenges

NGS technology brings opportunities for parallelizing genetic testing utilizing targeted gene panels, whole-exome or whole-genome approaches. NGS is also changing the way in which labs, clinicians and gene testing service facilities work. Using NGS introduces new challenges for storing and accessing complex data, identifying clinically relevant and validated genetic variants, and providing high quality and consistent lab reports.

Labs need to maintain turn-around times, interpret hundreds or even thousands of genetic variants of varying significance, and guarantee clinical quality of the lab report. To keep ahead of volumes, labs need to automate and standardize their diagnostic workflow with state-of-the art tools.

Clinicians need to guarantee standard of care and confidently counsel, making it a necessity to have up-to-date and – where possible – clinically validated knowledge resources always available.

Hospitals and core facilities need integrated tools that work with technologies from multiple vendors, integrate with IT systems, and link to external referrers electronically, yet are flexible enough to handle technologies changing over time.

Store and explore, validate and automate

The BENCH lab NGS solution provides unparalleled feature functionality to support the four essential steps in robust and reliable NGS data analysis:

Store and annotate genomic variants and patient information: Manage storage complexity of large data volumes, large numbers of variants, samples and patients, including detailed phenotype information.

- Explore and identify disease mutations: Efficiently search and explore the genomic variant database and identify disease mutations. Automatically consult heterogeneous information sources, public databases and algorithms for interpretation. Build pipelines, explore and confirm diagnostic hypotheses.

- Validate clinical findings and interpretation workflows: Assist in validating clinical findings, set up automated analysis and variant triage pipelines, and clinically validate them on existing data sets before introducing them in routine practice.

- Automate lab reporting: Implement standard operating procedures for interpretation and reporting into automated clinical use. Automatically and confidently generate lab reports. Integrate with LIMS and EHR systems.

Beta test use program

The product was created to the same standard as BENCH lab CNV, Cartagenia´s proven product for structural variant analysis on array CHG data, which has enjoyed tremendous success over the past years. BENCH lab NGS similarly focuses on increasing lab efficiency and supporting the daily routine of diagnostic labs.

Part of the product validation process was done in close collaboration with key customers. Cartagenia runs a comprehensive beta test program, in which over 10 leading labs worldwide are participating, validating the product in multiple clinical domains and utilizing a range of sequencing strategies. In the beta test program, participating labs provide NGS data (gene panels, exomes and whole genomes), patient case information, and operational diagnostic workflow descriptions.

GeneDx (Gaithersburg, MD) is validating BENCH lab NGS as an efficient storage system for variants annotated by an in-house pipeline for its Next Gen Sequencing panels. Use cases include phenotype driven search of annotated variants to identify clinically relevant mutations in context of multiple testing indications, with integration of results / findings to a reporting system, and a joint analysis of both CNV assay results and molecular variations, allowing encompassing search and reporting across genotyping platforms.

The Genome Diagnostics unit of the Medical Genetics center at UMC Utrecht, The Netherlands, is validating diagnostic workflows in Primary Immune Deficiencies (PID), for which they have developed a target capture kit, incorporating phenotype in variant selection and triage. With UMC Utrecht and 7 collaborating large clinical genetics groups, Cartagenia is standardizing requisition forms to tailor PID clinical information capture, for subsequent incorporation into phenotype-driven variant triage and classification.

In a parallel track, Cartagenia and UMC Utrecht are co-developing general purpose diagnostic workflows around a 300+ gene targeted sequencing assay (covering diagnostically validated as well as putative genes), using masking functionality and the in silico assay design system available in BENCH lab NGS. This allows variant sub-setting and tailored report automation targeted to a specific pathology or reason for referral.

At the DNA Diagnostics Laboratory of the Department of Clinical Genetics at AMC, Amsterdam, The Netherlands, a similar domain-specific approach was taken, with a primary focus on cardiomyopathies. A key issue in disease-specific variant interpretation is dealing with managed variant lists, where a lab can annotate previously seen variants and automate reporting when variant observations occur in new samples. With AMC, attention was also paid to developing score-card based methods effectively combining multiple algorithms that provide effect prediction scores, strengthening the quality of overall effect prediction for variants of unknown significance.

With the DNA Diagnostics lab at the Hospices Civils de Lyon, CHU Lyon, France, Cartagenia is looking into supporting analysis of large families for diagnosis of autosomal or X-linked recessive disorders. Other unique areas of collaboration include comparative analysis in cancer versus normal tissue.

Amongst a number of other applications, Cartagenia is working with Centre for Medical Genetics at the University Hospital of Brussels (UZ Brussel), Belgium, to support analysis of primary cardiac arrhythmias and mitochondrial disorders. The latter are more challenging because of the wide clinical spectrum, the mode of inheritance and the different types of variants (nuclear and mitochondrial homo- versus heteroplasmic mutations).

With the Genomics Core at Life and Brain GmbH, Bonn, Germany, Cartagenia is working is the area of Oncology. Although multiple specific pathologies were jointly addressed, the most prominent use case with L&B is on sequencing and interpreting a panel of relevant genes involved in Familiar Adenomatous Polyposis (FAP). The BENCH lab NGS platform is tailored towards automated in-silico masking, variant reporting on known disease-bearing mutations, and automated clinical reporting on diagnostically relevant findings.

Herman Verrelst, CEO of Cartagenia: “I would like to explicitly thank our customers and partners for providing us with a wealth of input and clinical information. Through-out the process, we were tremendously motivated by the consistent positive feedback from our beta users. We have now a mature product that we bring to the market with the utmost confidence. The BENCH lab NGS solution was developed under stringent requirements of an ISO 13485 certified Quality Management System and will be marketed in the USA as an exempt Class 1 Medical Device, subject to FDA general controls and software quality system regulations for medical devices.”

The BENCH lab NGS solution is immediately available. Cartagenia will be exhibiting, discussing and presenting the new system at the ACMG 2012 Clinical Genetics Meeting at the Charlotte Convention Center, March 27-31, BOOTH #229.

More information can be found at:

www.cartagenia.com/products or www.cartagenia.com/ACMG2012

About Cartagenia

Cartagenia supplies diagnostic knowledge, software and database systems, and related services to genetic labs and clinicians, enabling them to perform clinically relevant genetic analyses quickly and efficiently, and offer patients and carers high-quality genetic interpretation and counselling. (www.cartagenia.com)

Contact:

CARTAGENIA

Herman Verrelst

CEO Cartagenia

Technologielaan 3

3001 Leuven

T +32 16 40 40 66

E herman.verrelst@cartagenia.com

www.cartagenia.com