The classic website will no longer be available as of June 25, 2024. Please use the modernized
Working… Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT05295277
Recruitment Status : Recruiting
First Posted : March 25, 2022
Last Update Posted : August 7, 2023
University of Rochester
Columbia University
Greenwood Genetic Center
Praxis Genomics
Augusta University
Medical College of Wisconsin
University of Iowa
Information provided by (Responsible Party):
Bionano Genomics

Brief Summary:
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.

Condition or disease Intervention/treatment
Developmental Disability Intellectual Disability Autism Spectrum Disorder Congenital Anomaly Fragile X Syndrome Facioscapulohumeral Muscular Dystrophy 1 Other: Standard of care genetic testing group

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.

Layout table for study information
Study Type : Observational
Estimated Enrollment : 1000 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Validation of Optical Genome Mapping for the Identification of Constitutional Genomic Variants in a Postnatal Cohort
Actual Study Start Date : November 30, 2020
Estimated Primary Completion Date : March 31, 2024
Estimated Study Completion Date : June 30, 2024

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.

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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.

Biospecimen Retention:   Samples With DNA
Whole blood or banked lymphoblastoid cell lines (LCLs) will be sent to Bionano Genomics for sample blinding. Specimens are aliquoted, banked, and stored frozen. The specimens will be used for OGM testing or follow up testing using standard of care test methods, as needed and determined by the study protocol.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
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.

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT05295277

Layout table for location contacts
Contact: Alex Hastie, PhD 267-315-0914
Contact: Megan Martin, MS 801-931-6203

Layout table for location information
United States, Georgia
Praxis Genomics Active, not recruiting
Atlanta, Georgia, United States, 30328
Augusta University Research Institute Active, not recruiting
Augusta, Georgia, United States, 30912
United States, Iowa
University of Iowa Hospitals & Clinics, Molecular Pathology Active, not recruiting
Iowa City, Iowa, United States, 52242
United States, New York
Columbia University Irving Medical Center Active, not recruiting
New York, New York, United States, 10032
DNA Microarray CGH Laboratory, Department of Pathology, University of Rochester Medical Center Active, not recruiting
W. Henrietta, New York, United States, 14586
United States, South Carolina
Greenwood Genetic Center Recruiting
Greenwood, South Carolina, United States, 29646
Principal Investigator: Steven A. Skinner, MD         
United States, Utah
Lineagen (A Bionano Genomics Company) Recruiting
Salt Lake City, Utah, United States, 84109
United States, Wisconsin
Medical College of Wisconsin Active, not recruiting
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Bionano Genomics
University of Rochester
Columbia University
Greenwood Genetic Center
Praxis Genomics
Augusta University
Medical College of Wisconsin
University of Iowa
Layout table for investigator information
Principal Investigator: Alka Chaubey, PhD, FACMG Bionano Genomics
Publications of Results:
Iqbal MA, Broeckel U, Levy B, Sinner S, Sahajpal N, Rodriguez V, Stence A, Awayda K, Scharer G, Skinner C, Stevenson R, Bossler A, Nagy PL, Kohle R. Multi-site technical performance and concordance of optical genome mapping: constitutional postnatal study for SV, CNV, and repeat array analysis. MedRxiv (pre-print). 2021 Dec 30; doi:

Other Publications:
Chaisson MJP, Sanders AD, Zhao X, Malhotra A, Porubsky D, Rausch T, Gardner EJ, Rodriguez OL, Guo L, Collins RL, Fan X, Wen J, Handsaker RE, Fairley S, Kronenberg ZN, Kong X, Hormozdiari F, Lee D, Wenger AM, Hastie AR, Antaki D, Anantharaman T, Audano PA, Brand H, Cantsilieris S, Cao H, Cerveira E, Chen C, Chen X, Chin CS, Chong Z, Chuang NT, Lambert CC, Church DM, Clarke L, Farrell A, Flores J, Galeev T, Gorkin DU, Gujral M, Guryev V, Heaton WH, Korlach J, Kumar S, Kwon JY, Lam ET, Lee JE, Lee J, Lee WP, Lee SP, Li S, Marks P, Viaud-Martinez K, Meiers S, Munson KM, Navarro FCP, Nelson BJ, Nodzak C, Noor A, Kyriazopoulou-Panagiotopoulou S, Pang AWC, Qiu Y, Rosanio G, Ryan M, Stutz A, Spierings DCJ, Ward A, Welch AE, Xiao M, Xu W, Zhang C, Zhu Q, Zheng-Bradley X, Lowy E, Yakneen S, McCarroll S, Jun G, Ding L, Koh CL, Ren B, Flicek P, Chen K, Gerstein MB, Kwok PY, Lansdorp PM, Marth GT, Sebat J, Shi X, Bashir A, Ye K, Devine SE, Talkowski ME, Mills RE, Marschall T, Korbel JO, Eichler EE, Lee C. Multi-platform discovery of haplotype-resolved structural variation in human genomes. Nat Commun. 2019 Apr 16;10(1):1784. doi: 10.1038/s41467-018-08148-z.

Layout table for additonal information
Responsible Party: Bionano Genomics Identifier: NCT05295277    
Other Study ID Numbers: 20203726
First Posted: March 25, 2022    Key Record Dates
Last Update Posted: August 7, 2023
Last Verified: August 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Bionano Genomics:
Validation study
Comparison study
New technology compared to standard of care
Additional relevant MeSH terms:
Layout table for MeSH terms
Muscular Dystrophies
Muscular Dystrophy, Facioscapulohumeral
Intellectual Disability
Fragile X Syndrome
Congenital Abnormalities
Autism Spectrum Disorder
Developmental Disabilities
Child Development Disorders, Pervasive
Neurodevelopmental Disorders
Mental Disorders
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Neurobehavioral Manifestations
Neurologic Manifestations
Mental Retardation, X-Linked
Sex Chromosome Disorders
Chromosome Disorders
Genetic Diseases, X-Linked
Heredodegenerative Disorders, Nervous System