Validation of Optical Genome Mapping for the Identification of Constitutional Genomic Variants in a Postnatal Cohort

August 4, 2023 updated by: Bionano Genomics
The purpose of this research use only (RUO) study is to detect genomic structural variants (SVs) in human DNA by Optical Genome Mapping (OGM) using the Bionano Genomics Saphyr system. SVs are a type of genetic alternation that includes deletions, duplications, and both balanced and unbalanced rearrangements (ex: inversions or translocations), as well as specific repeat expansions and contractions. The results of OGM analysis will be compared to prior clinical genetic test results to determine how OGM compares to current standard of care (SOC) clinical test methods such as chromosomal microarray analysis (CMA), karyotyping, Southern blot analysis, polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), and/or next generation sequencing (NGS), etc.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Optical genome mapping (OGM) is an emerging next-generation cytogenomic tool that enables a comprehensive analysis of structural variants (SVs) in the genome. OGM, in its current iteration, is performed on the Saphyr system, which is developed and marketed by Bionano Genomics (San Diego, CA). OGM employs imaging of ultra-long DNA molecules (>150 kbp) that are labeled at a unique 6 base-pair sequence motif (CTTAAG) that occurs throughout the genome. The images of the labeled DNA molecules are used to generate a de novo assembly that can be compared to a reference genome to identify all classes of SVs, such as deletions, duplications, balanced/ unbalanced genomic rearrangements (insertions, inversions, and translocations), and repeat array expansions/contractions). In addition, a separate coverage-based algorithm enables the detection of genome-wide copy number analysis (similar to CMA), and the absence of heterozygosity (AOH) analysis. In the same assay, a concurrent or stepwise data analysis pipeline allows for sizing pathogenic CGG repeat expansions (consistent with fragile X syndrome) as well as D4Z4 repeat contractions which are consistent with facioscapulohumeral muscular dystrophy type 1 (FSHD1). Recently, in several studies, OGM has demonstrated excellent concordance with standard-of-care testing. Importantly, the OGM workflow can provide results within three-five days.

The aim of this double-blinded, multi-site, retrospective, observational, Institutional Review Board (IRB)-approved study is to evaluate the concordance of structural variant detection by OGM compared to standard of care tests (such as CMA, karyotyping, Southern blot analysis, PCR, FISH, and/or NGS, etc.), in a large cohort containing a variety of SVs including aneuploidies, intragenic and contiguous deletions, duplications, balanced and unbalanced translocations, inversions, isochromosomes, ring chromosomes, repeat expansions, repeat contractions, and more. This study is also designed to assess the sensitivity, specificity, and reproducibility of OGM analysis conducted at multiple sites, by numerous operators, and on different Saphyr instruments. Consensus testing and interpretation protocols were developed and implemented at all sites.

Study Type

Observational

Enrollment (Estimated)

1000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30328
        • Active, not recruiting
        • Praxis Genomics
      • Augusta, Georgia, United States, 30912
        • Active, not recruiting
        • Augusta University Research Institute
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Active, not recruiting
        • University of Iowa Hospitals & Clinics, Molecular Pathology
    • New York
      • New York, New York, United States, 10032
        • Active, not recruiting
        • Columbia University Irving Medical Center
      • W. Henrietta, New York, United States, 14586
        • Active, not recruiting
        • DNA Microarray CGH Laboratory, Department of Pathology, University of Rochester Medical Center
    • South Carolina
      • Greenwood, South Carolina, United States, 29646
        • Recruiting
        • Greenwood Genetic Center
        • Principal Investigator:
          • Steven A. Skinner, MD
    • Utah
      • Salt Lake City, Utah, United States, 84109
        • Recruiting
        • Lineagen (A Bionano Genomics Company)
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Active, not recruiting
        • Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Individuals will be recruited if they have standard of care genetic test results (such as CMA, karyotyping, Southern blot analysis, PCR, FISH, and/or NGS, etc.) to compare to optical genome mapping results.

Description

Inclusion Criteria:

  1. Individual with a genomic aberration identified by CMA, karyotyping, Southern blot analysis, PCR, FISH, and/or NGS or other standard of care (SOC) genetic testing technology whose clinical test results are available to compare with results from OGM.
  2. Patients with prior negative SOC genetic testing results whose results are available to compare with results from OGM.

Exclusion Criteria:

  1. Any individual who opted-out of research at the testing laboratory.
  2. An individual whose genetic test contains the following variants: pathogenic sequence variants, abnormalities involving acrocentric p-arms and centromeres, below 20% for mosaicism, and tetraploidy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Retrospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Standard of care genetic testing group
Individuals with genomic test results from a standard of care (SOC) test (such as CMA, karyotyping, Southern blot analysis, PCR, FISH, and/or NGS, etc.) will be enrolled in the study to compare the SOC result to results from optical genome mapping.
Other: Standard of care genetic testing group
N/A - no intervention as this is an observational study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sensitivity/Concordance and specificity of OGM with standard of care testing for detection of structural variants.
Time Frame: Through study completion, an average of 1 year
OGM results are evaluated against the standard of care test and concordance (sensitivity and specificity) will be determined.
Through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Reproducibility and identification of structural variants beyond the limit of detection of standard of care methods.
Time Frame: Through study completion, an average of 1 year
Inter-site as well as inter and intra-run variability of OGM will be assessed by reproducibility studies.
Through study completion, an average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bionano Genomics

Collaborators

Columbia University
University of Iowa
Medical College of Wisconsin
Augusta University
University of Rochester
Greenwood Genetic Center
Praxis Genomics

Investigators

  • Principal Investigator: Alka Chaubey, PhD, FACMG, Bionano Genomics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 30, 2020

Primary Completion (Estimated)

March 31, 2024

Study Completion (Estimated)

June 30, 2024

Study Registration Dates

First Submitted

March 7, 2022

First Submitted That Met QC Criteria

March 15, 2022

First Posted (Actual)

March 25, 2022

Study Record Updates

Last Update Posted (Actual)

August 7, 2023

Last Update Submitted That Met QC Criteria

August 4, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20203726

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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