Bionano Genomics capped off its 2022 Symposium with presentations demonstrating that the combination of optical genome mapping (OGM) and next-generation sequencing (NGS) can reveal more answers in genetic disease and cancer research than ever before. The combination of OGM and NGS provides the genomics community with the most scalable and comprehensive way to view genome variations.

Today’s nine expert speakers shared multiple examples of how the combination of mapping and sequencing gives a more complete picture of the genome. OGM uses long-read sequencing to detect insertions, deletions, inversions, duplications, translocations, and copy number variations to complement NGS, which relies on short-read sequences and has significant limitations identifying most large SVs.

“During the final session of our 2022 Symposium, we really saw how the synergistic power of OGM + NGS reveals more answers that matter – truly transforming the way the world sees the genome,” said Alka Chaubey, PhD, FACMG, and chief medical officer at Bionano Genomics.

The combined approach of OGM and NGS changed the way researchers approached workflows for evaluation of hematologic malignancies. In his presentation, Dr. Ravindra Kolhe, from the Medical College of Georgia at Augusta University, shared a unique approach that added value to the existing NGS workflow by combining OGM with a 523-gene panel on NGS. The combination resulted in additional information beyond what a smaller 54-gene panel, karyotype and fluorescent in situ hybridization (FISH) could detect, including single-nucleotide variants (SNVs), copy number variants (CNVs) and translocations. Dr. Kolhe also shared one of the first visualizations of the combination of OGM and sequencing data using BioDiscovery’s N_xClinical software, which enables a streamlined interpretation for both data types in an integrated simplified view for faster time to results.

In her presentation, Dr. Gordana Raca, from Children’s Hospital Los Angeles, shared how OGM and capture-based transcriptome sequencing (RNA-Seq) enabled an increase in variant detection and molecular subtyping for previously unknown cases in pediatric B-cell acute lymphoblastic leukemia (B-ALL). Use of these techniques allowed discovery of novel fusions associated with pediatric B-ALL and helped elucidate the chromosomal mechanism through which these abnormal fusions were generated.

In a third presentation, Dr. Rashmi Kanagal Shamana, from MD Anderson Cancer Center, discussed a comprehensive assessment of a large myelodysplastic syndrome (MDS) cohort using OGM and a targeted NGS panel. Results showed that the high throughput whole genome structural variant profiling enabled by OGM revealed a much higher frequency of SVs in MDS, half of which were not detected by conventional karyotyping. These cryptic clinically significant SVs were seen in approximately 30% of MDS patients in her research study and resulted in change in the prognostic category for 10% of the subjects.

Applications of OGM + NGS to investigations of genetic disease revealed new disease-causing variants and showed improved performance over other methods. Dr. Kornelia Neveling, from Radboud University Medical Center, presented on how OGM and long-read HiFi genome sequencing helped to identify different types of hidden structural variants in three subjects with inherited retinal diseases.

Dr. Laila El-Khattabi, from Assistance Publique–Hôpitaux de Paris (AP-HP), presented findings from her study using OGM to characterize apparently balanced SVs found in people with developmental disorders. Their molecular characterization is essential to establishing proper genotype-phenotype correlations, which is not possible with current cytogenetic techniques. Short-read whole genome sequencing (srWGS) is capable of detecting balanced rearrangements, at a resolution down to one base pair, but has a high failure rate. Dr. El-Khattabi’s results suggested that OGM may allow for a higher detection rate of SVs and complement srWGS in developmental pathologies for a more complete analysis of the genome.

In cancer research, OGM + NGS were used to characterize both germline and tumor genetic aberrations. During her presentation, Dr. Mariangela Sabatella, from Princess Máxima Center for Pediatric Oncology, described a case in which OGM revealed an underlying germline mutation in a family with two siblings who were neonatally diagnosed with atypical teratoid rhabdoid tumor (ATRT). This rare pediatric tumor is associated with biallelic inactivation of SMARCB1. Routine analysis did not identify any clear pathogenic SMARCB1 variants. OGM was the only method used by Dr. Sabatella that could identify the ATRT predisposing insertion of an SVA-E retrotransposon element of ~2.8 kb.

Dr. Jens Luebeck, from University of California San Diego, presented on how combining OGM and NGS revealed the complex structures of circular extrachromosomal DNA (ecDNA) and other genomic focal amplifications in cancer genomes, especially in tumors. These genetic changes are associated with lower patient survival and enhanced tumor evolution. Using a combination of OGM and NGS, Dr. Luebeck was able to reveal megabase-scale maps of ecDNA, ecDNA-derived homogenous staining regions (HSRs), and other focal amplifications in multiple cancer cell lines, demonstrating the combined power of these methods.

Today’s speakers:

Kornelia Neveling, PhD

Translational Genomics Scientific Researcher, Radboud University Medical Center in the Netherlands

“Optical genome mapping: different types of hidden SVs in families with inherited retinal diseases”

Mariangela Sabatella, PhD

Princess Máxima Center for Pediatric Oncology

“Enlightening the dark matter of the genome: Optical genome mapping identifies a germline retrotransposon insertion in SMARCB1 in two siblings with Atypical Teratoid Rhabdoid Tumors”

Gordana Raca, PhD

Director of Cytogenomics, Associate Professor of Pathology and Laboratory Medicine, Children’s Hospital Los Angeles

“Optical Genome Mapping and Capture-Based Transcriptome Sequencing (RNA-Seq) Enable Comprehensive Genomic Characterization of Pediatric B-lymphoblastic Leukemias”

Arran Constatine, BSc

Scientist Manufacturing Science and Technology Department, bit.bio

“Cytogenetic QC at bit.bio”

Saumyaa Saumyaa, PhD

Senior Scientist, Gene Editing Safety Group, AstraZeneca

“Detection and characterization of on- and off-target integration of foreign DNA in the host genomes, for therapeutic cell and gene therapy development, using novel Optical DNA mapping technology by Bionano Genomics”

Laila El-Khattabi, PharmD, PhD

Associate Professor, Genomic Technologies and Immuno-Genomics, APHP Université de Paris

“Molecular characterization of genome structural variants in developmental disorders: Comparison between optical genome mapping and short read whole genome sequencing”

Jens Luebeck PhD

Postdoctoral Researcher, Bioinformatics, University of California, San Diego

“Combined NGS and optical mapping reveal the complex structures of circular extrachromosomal DNA and other focal amplifications in cancer genomes”

Ravindra Kolhe, MD, PhD, FCAP

Associate Dean, Translational Research, Medical College of Georgia at Augusta University

“Clinical Utility of Combined Optical Genome Mapping and Comprehensive Genomic Sequencing in Robust Evaluation of Hematological Cancers”

Rashmi Kanagal Shamana, MD

Director, CLIA-certified Molecular Diagnostic Laboratory (Microarray section), MD Anderson Cancer Center

“A comprehensive assessment of a large Myelodysplastic Syndrome cohort at MD Anderson Cancer Center using Optical Genome Mapping and a targeted NGS panel”

Symposium presentations will be available online after January 14, 2022 at

https://www.labroots.com/ms/virtual-event/bngo2022