Optical Genome Mapping improves detection and streamlines analysis of structural variants in myeloid neoplasms.

Accurate diagnosis and risk stratification of hematological malignancies require disease-specific laboratory testing procedures involving the use of hematopathology, flow cytometry, molecular and cytogenetic testing. While individual laboratories develop unique workflows to accommodate volume, clinical needs and staffing, cytogenetic laboratories generally require a multitude of targeted and genome-wide tests that detect clinically relevant aberrations in hematologic malignancies. Specifically, the frequent use of multiple FISH panels coupled with concurrent chromosome analysis, can be both labor, and resource intensive.. Optical Genome Mapping (OGM) is a comprehensive cytogenetic solution for detecting structural variants with high resolution and increased accuracy for hematological malignancy subtypes at the DNA level without need of any cell culture regimens. A new software tool for analysis of OGM data called VIA (for Variant Intelligence Applications), provides an integrative analysis, interpretation and reporting solution for OGM and other datatypes. In this pilot study, we performed retrospective review of 56 datasets, representing 10 unique myeloid cases to assess multi-user (technologist and laboratory director) analyses and classification. Interpretation and reporting of OGM results were 100% concordant between reviewers for four cases with negative results by standard of care (SOC) testing. For the other six cases, five pathognomonic gene fusions identified by SOC assays were unanimously reported as Tier 1A variants. relevance not found by SOC methods in five of the six positive cases. Leveraging automatic pre-classification of variants and custom decision tree, the VIA software enabled to complete analysis with a mean technologist review time (variant analysis and initial tier determination) of 30.7 minutes. The analysis, interpretation, and reporting workflow described in this pilot study provides a framework for standardized and streamlined reporting of clinically significant variant in myeloid malignancies using VIA. ### Competing Interest Statement TS is employed by Bionano Labs, a wholly owned subsidiary of Bionano Genomics RK has received honoraria, and/or travel funding, and/or research support from Illumina, Cepheid, ALDA, OCDdx, Roche, Agena, Bionano, PGDx (LabCorp), Novartis, AbbVie, AstraZeneca and Lilly. ### Funding Statement This study was funded in part by Bionano Genomics, inc. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: IRB and consent IRB-20212956 Bionano Genomics Inc., San Diego, CA, USA IRB 00007527 University of Rochester Medical Center Office for Human Subject Protection IRB A #00000150 (HAC IRB # 611298) Medical College of Georgia, Augusta University, Augusta, GA, USA I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data will be made available upon reasonable request and in accordance with IRB protocols.