This year’s European Society of Human Genetics (ESHG) Conference took place in Gothenburg, Sweden, and was a breakthrough for Bionano. Several oral and poster presentations compared Bionano optical mapping to clinical cytogenetics standard of care in leukemia and constitutional disease testing, and the results surpassed all expectations! We have videos of the three most exciting talks, and links to six posters that were presented at ESHG below, but we can give away the conclusion now: Next-Generation Cytogenetics is Here!
Three oral presentations featured extensive Bionano data. First up was Bionano’s Sven Bocklandt, PhD, Director of Scientific Affairs, who gave a talk on “New developments in long read optical mapping enable novel applications for cancer and genetic disease,” summarizing recent updates to the Bionano platform and giving an overview of recent publications that use Bionano data for the detection of structural variation in human genomes. Dr. Alexander Hoischen, PhD, Associate Professor, Genomic Technologies & Immuno-genomicsat Radboud University Medical Center in the Netherlands, gave an update on their study comparing Bionano optical mapping with Saphyr to the current medical genetics workflows for leukemias and various genetic disorders. As part of a technical validation effort with the goal of implementing Bionano mapping in the clinical process in the near term, the Radboud team is running 100 leukemia genomes consisting of Chronic Myelogenous Leukemia (CML) and Acute Lymphoblastic Leukemia (ALL) among other hematologic malignancies, and 50 samples with constitutional cytogenetic abnormalities on Saphyr. Of the 36 samples analyzed so far, Bionano detected ALL clinically reported variants with variant allele fraction larger than 10% in leukemia and identified ALL known aberrations in the constitutional cases. The clinically relevant variants detected by Bionano had previously been identified by a combination of three long-established clinical diagnostic methods, chromosomal microarray, karyotype, and FISH. Watch his talk here: “Optical mapping enables next generation cytogenetics— applications in medical genetics”.
Last up was, Dr. Laila El-Khattabi, PharmD, PhD, from Hôpital Cochin – Paris Descartes University, who presented results where Saphyr detected a wide variety of balanced and unbalanced chromosomal abnormalities that occur in developmental disorders such as autism and developmental delay, and reproductive disorders such as male infertility and recurrent pregnancy loss, as part of a 30 sample clinical validation study. Of the 27 samples run on Saphyr so far, an initial analysis detected the clinically relevant variants in 25 out of 27 samples. Of the two that were missed, one included a translocation that other molecular methods had not been able to detect either because of its proximity to the centromere, and one complex aberration that was partially but not fully resolved by Bionano alone. Several balanced translocations detected by Bionano had been missed by whole genome sequencing analysis. The clinically relevant variants detected by Bionano had previously been identified by a combination of karyotype and chromosomal microarray in a clinical setting, and whole genome sequencing in a research setting. Watch her presentation here: “Using next generation mapping to detect balanced as well as unbalanced structural variants in reproductive and developmental diseases”.
A study titled “Evaluation of the Bionano optical mapping technology as a replacement of conventional cytogenetics in a diagnostic setting,” was presented by Charlotte Keith from Western General Hospital in Edinburgh, Scotland. In the study, the authors compared Bionano optical mapping to karyotyping and CMA on benchmark samples, including balanced translocations and large deletions. In one case, the higher resolution of optical mapping was able to define the breakpoint of a translocation to within a gene, and demonstrated that the translocation truncated it. The authors reported that they are preparing a large-scale validation to enable clinical use of the Bionano Saphyr system. Her poster is here: “Evaluation of the Bionano optical mapping technology as a replacement of conventional cytogenetics in a diagnostic setting”
In a poster titled, “Next generation cytogenetics in medical genetics with high-resolution optical mapping,” Dr. Tuomo Mantere and colleagues from Radboud University Medical Center are reporting initial results comparing optical mapping with a suite of traditional cytogenetic methods – fluorescence in situ hybridization (FISH), karyotyping and chromosomal microarrays (CMA). They are concluding that, “optical mapping identified all the previously known clinically relevant aberrations from the analyzed samples.” Additionally, they were able to find additional abnormalities and resolve the breakpoints with much higher resolution. His poster is here: “Next-generation cytogenetics in medical genetics with high-resolution optical mapping”
The identification of pathogenic structural variants in complex cancer genomes like the ones presented by the teams from Radboud, Cochin and Wetern Univeristy Edinburgh is helped by the recent release of Bionano’s new and improved analysis software, Bionano Access and Bionano Solve. Specifically, Bionano’s new Rare Variant Pipeline allows for the detection of all major structural variant types with high sensitivity and precision present at an allele fraction of just five percent, meaning that variants present in just a small fraction of cells in a complex, heterogeneous tumor sample can still be detected – a feat that is impossible with sequencing based analysis methods. Bionano scientists presented initial results generated with this pipeline, and detailed the recently released fast isolation protocol for ultra-high molecular weight DNA, Bionano Prep SP, in various presentations at ESHG as well:
“Sensitive detection of low allele fraction structural variants in clinical cancer samples”
Yannick Delpu, PhD, Bionano Genomics
“Solution-based isolation of ultra-high-molecular weight (UHMW) DNA from fresh/frozen human blood and cultured cells in less than 3 hours”
Goran Pljevaljcic, PhD, Bionano Genomics
“Comprehensive detection of germline and somatic structural mutation in cancer genomes by Bionano Genomics optical mapping”
Sven Bocklandt, PhD, Bionano Genomics
“Optical genome mapping for detection of structural variants in constitutional disease”
Alex Hastie, PhD, Bionano Genomics
The incredible feedback these talks and posters received at ESHG had us fired up for the 12th European Cytogenomics Conference in Salzburg as well – Next-Generation Cytogenetics surely made a splash in Europe!