White Paper – NGP Validation (June 2019)

Validation Study of the Integration of Next-Generation Phenotyping in Exome Analysis

A collaboration between Greenwood Genetic Center (SC, USA) and FDNA (MA, USA)

 

Summary

Next-generation phenotyping (NGP) technologies capture, structure, and analyze complex phenotypic

information to produce actionable genomic insights. DeepGestalt is an NGP technology that currently

supports more than 300 specific genetic syndromes and syndrome groups, representing 45% of cases

solved by WES. Next-generation sequencing (NGS) augmented by NGP results in more efficient and

accurate diagnoses.

 

In this study, we show that:

• Integration of NGP in the variant analysis workflow dramatically increases diagnostic yield and

efficiency as compared to traditional methods of variant prioritization, placing causative genes in ≤

5th rank in 50% of cases;

• NGP increases the number of top-ranked causative genes in both “easily solved” and “challenging”

cases, with an overall improvement in ranking across all cases;

• NGP ranking among cases supported by DeepGestalt is even more impressive, showing 67%

ranked in the top 5, compared to 11% based on GGC and CADD ranks;

• NGP may enable prioritization of causative variants independent of parental data, decreasing costs

by reducing the need to complete parental WES and increasing diagnostic yield by enabling

diagnosis of cases where parental samples are unavailable;

• Expanding NGP analysis beyond the face (brain MRIs, skeletal radiographs, fundoscopy) will

increase the amount of syndromes supported.

Read the full White Paper

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    Assoc. Prof. Ibrahim Akalin, MD, Medical Geneticist from the Istanbul Medeniyet University, Istanbul, Turkey

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    Professor of Pediatrics UCSF, Adjunct Professor of Pediatrics Stanford

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    Chief, Division of Medical Genetics A.I. duPont Hospital for Children

  • FDNA's idea of incorporating several dysmorphology resources (OMIM, GeneReviews), supported by their visual analytic technology, will be able to improve researching of genetic syndromes - all within a single mobile app.

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    Assistant Professor Pediatrics at Mission Fullerton Genetics

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    Associate Professor of Pediatrics Director, Division of Human Genetics Department of Pediatrics Warren Alpert Medical School of Brown University

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    Rady Children's Specialists of San Diego

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    Chairman (Retired) of The Simon Winter Institute for Human Genetics at Bnai-Zion Medical Center, Technion-Rappaport Faculty of Medicine

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    Clinical Geneticist at the Hospital Santa Maria, CHLN, Lisbon, Portugal