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Key Publications

key publication

High-resolution structural variant profiling of myelodysplastic syndromes by optical ...

Kanagal-Shamanna Lab

MD Anderson Cancer Center

August 1, 2022

Leukemia

doi: https://doi.org/10.1038/s41375-022-01652-8

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Key Points:

  • 101 consecutive MDS samples were evaluated with traditional cytogenetic methods (karyotyping, FISH, CMA), an 81-gene NGS panel, and OGM
  • OGM found nearly double the number of clinically relevant pathogenic variants compared to traditional cytogenetics
  • OGM findings could inform different prognostic risk classification or identify important additional variants in 28% of study participants
  • Changes to CCSS and IPSS-R risk scores in 21% and 17% of subjects, respectively.
  • Additional 13% of samples had additional alternations researchers suggest could be used for therapy selection/response and disease monitoring
  • The combination of OGM and NGS resulted in the detection of at least one clinically significant clonal abnormality in 97 of 101 samples
key publication

Clinical validation and diagnostic utility of optical genome mapping in prenatal ...

Kolhe Lab

Augusta University

Preprint: May 16, 2022

medRxiv

doi: https://doi.org/10.1101/2022.05.11.22274975

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Key Points:

  • Retrospective validation study analyzing 94 unique amniocentesis samples previously characterized with karyotyping, FISH, and/or CMA
  • OGM was 100% concordant with findings from traditional cytogenetics across multiple types of chromosomal aberrations (aneuploidies, triploidy, deletions, duplications, translocations, isochromosomes, markers, AOH)
  • OGM detected 64 additional reportable SVs in 43 samples
key publication

Optical genome mapping for structural variation analysis in hematologic ...

Adam C. Smith — University Health Network, Toronto, Rashmi Kanagal-Shamanna — MD Anderson, Kornelia Neveling — Radboud UMC

May 12, 2022;1-8.

Am J Hematol

doi: https://doi.org/10.1002/ajh.26587

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Key Points:

  • Highlights the performance of OGM in acute myeloid leukemia, myelodysplastic syndromes, and B cell acute lymphoblastic leukemia
  • Illustrates how the OGM workflow can solve common challenges in testing for hematologic malignancies
  • Discusses the strengths and weaknesses of OGM compared to traditional methods
key publication

16p13.11p11.2 triplication syndrome: a new recognizable genomic disorder characterized by ...

Malan Lab

Hôpital Necker-Enfants Malades

April 30, 2022:712-720.

Eur J Hum Genet

doi: https://doi.org/10.1038/s41431-022-01094-x

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Key Points:

  • Report of two unrelated subjects with a de novo 16p13.11p11.2 triplication associated with a 16p11.2 duplication, detected by CMA
  • Short-read WGS could not map any of the breakpoints
  • OGM determined the relative orientation of the triplicated and duplicated segments as well as the genomic positions of the breakpoints
  • Insights from OGM allowed authors to unravel the mechanism of these complex chromosomal rearrangements involving segmental duplications, propose a mechanism, and report a new clinically recognizable genomic disorder”
key publication

Optical Genome Mapping Improves Genetic Diagnosis in Chronic Granulomatous ...

Xiaochuan Wang Lab

Children’s Hospital of Fudan University

Preprint: February 22, 2022

Research Square

doi: https://doi.org/10.21203/rs.3.rs-1290086/v1

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Key Points:

  • Case series evaluating three subjects with clinically confirmed chronic granulomatous disease that were negative by NGS (panel and WES)
  • OGM was performed and identified a novel pathogenic ~1.5 kbp deletion in a causative gene in 1/3 subjects
  • Demonstrates ability to identify disease-causing variants missed by sequencing technologies”
key publication

Optimizing the diagnostic workflow for acute lymphoblastic leukemia by optical genome ...

Dewaele Lab

University Hospitals Leuven

April 2022;97:548-561.

Am J Hematol

doi: https://doi.org/10.1002/ajh.26487

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Key Points:

  • Evaluated 41 samples of acute lymphoblastic leukemia (ALL): 29 B-ALL; 12 T-ALL
  • OGM detected all recurrent CNVs and SVs as well as additional recurrent SVs and resulting fusions
  • While traditional techniques (karyotype, FISH, MLPA, array) could assign only 23 samples to a major cytogenetic risk group, researchers conclude that OGM data would allow assignment of 32 subjects, potentially improving risk stratification
key publication

Optical genome mapping reveals additional prognostic information compared to conventional ...

Nguyen and Vangala Labs

Ruhr-University BochumInt

January 22, 2022;150(12);1998-2011.

J Cancer

doi: https://doi.org/10.1002/ijc.33942

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Key Points:

  • Evaluated OGM performance in 27 samples from subjects with AML or MDS who underwent routine cytogenetic diagnostics (karyotype, FISH and RT-PCR when indicated)
  • OGM detected 31% more European Leukemia Net (ELN) and recurrent myeloid abnormalities compared to karyotyping and FISH
  • OGM also found abnormalities in 35% more samples than karyotyping, and in 67% of samples, the karyotype could be redefined by OGM. OGM refinement of the karyotype resulted in putative changes to the ELN risk classifications used in determining treatment plans
key publication

Clinical Utility of Combined Optical Genome Mapping and 523-gene Next Generation ...

Kolhe Lab

Augusta University

Preprint: Jan 17, 2022

medRxiv

doi: https://doi.org/10.1101/2022.01.15.22269355

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Key Points:

  • Evaluated the use of OGM and a 523-gene NGS panel for genomic profiling of 15 myeloid tumors and compared results to karyotyping, FISH, and a 54-gene NGS panel
  • Results demonstrated 100% analytical concordance of OGM and the 523-gene NGS panel for variants found with traditional methods
  • In addition, OGM better characterized structural variants (SVs) previously reported by karyotyping in five samples and identified additional translocations and 11 CNVs
  • Demonstrated the combination of OGM and NGS is beneficial for comprehensive genomic profiling of myeloid neoplasm and NxClinical software enables simultaneous visualization and CNV confirmation
key publication

Multi-site Technical Performance and Concordance of Optical Genome Mapping: ...

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

Preprint: Dec 27, 2022

medRxiv

doi: https://doi.org/10.1101/2021.12.27.21268432

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Key Points:

  • Interim readout of an ongoing multisite study comparing the performance of OGM in postnatal samples with known genetic aberrations from prior testing with karyotype, FISH, and/or CMA
  • OGM had full concordance with previous findings in 97.7% (214/219) and partial concordance in 2.3% (5/219) of samples with multiple CNVs
  • Additional metrics establish strong technical performance, with a first-pass success rate of 94% (311/331 samples), a final pass rate of 99.1%, a reproducibility of analytical QC of 98.8% (171/173 replicates), and an inter-site reproducibility of pathogenic variant calls of 100% (16/16 replicates)
key publication

Marfan Syndrome Caused by Disruption of the FBN1 Gene due to A Reciprocal Chromosome ...

Gläser Lab

University of Freiburg

Nov 21, 2022;12(11):1836.

Genes

doi: https://doi.org/10.3390/genes12111836

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Key Points:

  • Case report of a family with clinically diagnosed Marfan syndrome with no pathogenic variants identified on NGS analysis of FBN1 gene, but with a reciprocal balanced translocation between chromosomes 2 and 15
  • OGM was performed and mapped the breakpoint within the FBN1 gene on chromosome 15 — later confirmed by targeted sequencing — disrupting the gene and likely explaining the observed phenotype
  • First report of a reciprocal translocation in the FBN1 gene associated with a typical Marfan syndrome presentation”
key publication

Application of full-genome analysis to diagnose rare monogenic ...

Shieh, Penon-Portmann, and Wong Labs

University of California – San Francisco

Sept 23, 2021;6(77)

Genom Med

doi: https://doi.org/10.1038/s41525-021-00241-5

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Key Points:

  • Describes a Full-Genome Analysis (FGA) approach using NGS linked-read sequencing and OGM to evaluate full spectrum of genetic variation in inherited genetic disorders
  • FGA was used in 50 subjects previously undiagnosed by either trio whole exome sequencing (23/50) and/or array (43/50)
  • FGA demonstrated an overall rate of detecting pathogenic variants of 40% (20/50) and identified candidate variants in 60% (18/30) of the remaining subjects. Lastly, FGA identified SVs and small variants in 8 of the 23 subjects missed by trio WES”
key publication

Optical genome mapping identifies a germline retrotransposon insertion in SMARCB1 in two ...

Sabatella and Kuiper Labs

Princess Maxima Centre for Pediatric Oncology, Radboud University Medical Center

October 2021;255:202–211.

J Pathol

doi: https://doi.org/10.1002/path.5755

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Key Points:

  • Case report of a family with two siblings born from healthy parents who were both neonatally diagnosed with atypical teratoid rhabdoid tumor (ATRT), associated with acquired homozygosity of SMARCB1
  • WES and WGS failed to identify germline or somatic SMARCB1 pathogenic mutations• OGM detected an insertion of ~2.8 kb within intron 2 of SMARCB1
  • Further characterization with long-read sequencing identified this insertion to be a SINE-VNTR-Alu, subfamily E (SVA-E) retrotransposon element, which was present in a mosaic state in the mother
  • Demonstrates the power of OGM and long-read sequencing to identify genomic variations in high-risk cancer-predisposing genes that are refractory to detection with traditional techniques”
key publication

Optical genome mapping enables constitutional chromosomal aberration ...

El Khattabi and Hoischen Labs

Université de Paris, Hôpital Cochin, Radboud University Medical Center

August 5, 2022;108:1409-1422.

Am J Hum Genet

doi: https://doi.org/10.1016/j.ajhg.2021.05.012

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Key Points:

  • 85 constitutional samples with known chromosomal aberrations in the context of developmental and reproductive disorders
  • OGM had 100% concordance with traditional cytogenetic methods of karyotyping, FISH, and chromosomal microarray, detecting 99/99 aberrations
  • Aberration types included 7 aneuploidies, 19 deletions, 20 duplications, 34 translocations, 6 inversions, 2 insertions, 6 isochromosomes, 1 ring chromosome and 4 complex rearrangements”
key publication

Next-generation cytogenetics: Comprehensive assessment of 52 hematological malignancy ...

Hoischen Lab

Radboud University Medical Center

Aug 5, 2021;108(8):1423-1435.

Am J Hum Genet

doi: https://doi.org/10.1016/j.ajhg.2021.06.001

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Key Points:

  • Evaluated OGM performance in 52 myeloid and lymphoid samples with clinically relevant aberrations detected with karyotyping, FISH, and/or CMA (36 simple; 16 complex)
  • Found 100% concordance of OGM in samples that traditional methods characterized as simple (46/46 aberrations in 36 samples)
  • Also found full concordance in 14/16 samples that traditional methods characterized as complex, with the remaining 2 cases largely concordant, while revealing additional new structural variants, gene fusion events, and greater detail about the structure of previously observed variants
  • OGM identified 15 additional candidate balanced translocations in 8 samples (4 simple; 4 complex) leading to potential gene fusion
key publication

Detection of a mosaic CDKL5 deletion and inversion by optical genome mapping ends an ...

Shashi Lab

Duke University Medical Center (part of the Undiagnosed Diseases Network)

Jul 2021;9(7):e1665.

Mol Genet Genomic Med

doi: https://doi.org/10.1002/mgg3.1665

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Key Points:

  • Case report of a 4-year-old male with an epileptic encephalopathy of undiagnosed molecular origin
  • Extensive prior metabolic and genetic testing had been non-diagnostic, including chromosome analysis, CMA (Affymetrix Cytoscan HD array), an infantile epilepsy panel (sequencing and deletion/duplication analysis of 38 genes), mitochondrial genome sequencing, trio WES, and trio WGS
  • OGM identified a mosaic, de novo 90 kb deletion and inversion on the X chromosome disrupting the CDKL5gene, resulting in a diagnosis of X-linked dominant early infantile epileptic encephalopathy-2 after confirmation in a clinical laboratory
  • Demonstrates the use of OGM to identify a mosaic structural variant missed by other techniques
key publication

A National Multicenter Evaluation of the Clinical Utility of Optical Genome Mapping for ...

Multicenter: Columbia University, Mayo Clinic, Penn State, PathGroup, Legacy Health, Augusta University, Fred Hutchinson and MD Anderson Cancer Centers

Preprint: November 10, 2022.

medRxiv

doi: https://doi.org/10.1101/2020.11.07.20227728

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Key Points:

  • Evaluated OGM performance in 100 AML samples previously evaluated with karyotyping and FISH
  • OGM detected 100% of all clinically relevant SVs and CNVs previously detected by traditional methods
  • OGM provided important incremental data in 24% of cases: additional clinically relevant SVs above and beyond traditional methods in 11% of samples and refinement of the genomic structure analysis in another 13%
  • Researchers illustrated how OGM consolidated techniques recommended by clinical guidelines (WHO, ELN, NCCN) for detection of hallmark AML SVs

Publications

title date Authors
Scrutinizing pathogenicity of the USH2A c.2276 G > T; p.(Cys759Phe) ... February 13, 2023 Janine Reurink, Erik de Vrieze, Catherina H Z Li, Emma van Berkel, Sanne Broekman, Marco Aben, Theo Peters, Jaap Oostrik, Kornelia Neveling, Hanka Venselaar, Mariana Guimarães Ramos, Christian Gilissen, Galuh D N Astuti, Jordi Corominas Galbany, Janneke J C van Lith-Verhoeven, Charlotte W Ockeloen, Lonneke Haer-Wigman, Carel B Hoyng, Frans P M Cremers, Hannie Kremer, Susanne Roosing, Erwin van Wijk
The snapdragon genomes reveal the evolutionary dynamics of the S locus ... October 10, 2022 Sihui Zhu, Yu'e Zhang, Lucy Copsey, Dongfeng Zheng, Enrico Coen, Yongbiao Xue, Qianqian Han
Molecular and genetic mechanisms conferring dissolution of dioecy in Diospyros oleifera ... October 9, 2022 Peng Sun Jr., Soichiro Nishiyama Jr., Huawei Li Jr., Yini Mai Jr., Weijuan Han Jr., Yujing Suo Jr., Chengzhi Liang Sr., Huilong Du Jr., Songfeng Diao Jr., Yiru Wang Jr., Jiaying Yuan Jr., Yue Zhang Jr., Ryutaro Tao Sr., Fangdong Li Sr., Jianmin Fu Sr.
Optical genome mapping identifies clinically relevant genomic rearrangements in prostate ... October 8, 2022 Yeeun Shim, Jongsoo Lee, Jieun Seo, Cheol Keun Park, Saeam Shin, Hyunho Han, Seung-Tae Lee, Jong Rak Choi, Byung Ha Chung, Young Deuk Choi
A contiguous de novo genome assembly of sugar beet EL10 (Beta vulgaris ... October 8, 2022 J Mitchell McGrath, Andrew Funk, Paul Galewski, Shujun Ou, Belinda Townsend, Karen Davenport, Hajnalka Daligault, Shannon Johnson, Joyce Lee, Alex Hastie, Aude Darracq, Glenda Willems, Steve Barnes, Ivan Liachko, Shawn Sullivan, Sergey Koren, Adam Phillippy, Jie Wang, Tiffany Liu, Jane Pulman, Kevin Childs, Shengqiang Shu, Anastasia Yocum, Damian Fermin, Effie Mutasa-Göttgens, Piergiorgio Stevanato, Kazunori Taguchi, Rachel Naegele, Kevin Dorn
DNA in nanochannels – Theory and ... October 7, 2022 Karolin Krykholm, Vilhelm Muller, KK Sriram, Kevin D Dorfman, Fredrik Westerlund
Inversion polymorphism in a complete human genome ... October 6, 2022 David Porubsky, William T. Harvey, Allison N. Rozanski, Jana Ebler, Wolfram Höps, Hufsah Ashraf, Patrick Hasenfeld, Human Pangenome Reference Consortium (HPRC), Human Genome Structural Variation Consortium (HGSVC), Benedict Paten, Ashley D. Sanders, Tobias Marschall, Jan O. Korbel, Evan E. Eichler
Identification and characterization of two DMD pedigrees with large inversion mutations ... October 5, 2022 Chang Geng, Ciliu Zhang, Pidong Li, Yuanren Tong, Baosheng Zhu, Jing He, Yanhuan Zhao, Fengxia Yao, Li-Ying Cui, Fan Liang, Yang Wang, Yaru Wang, Hongshuai Jin, Dandan Lang, Shanlin Liu, Depeng Wang, Min S. Park, Lin Chen, Jing Peng, Yi Dai
Chromosome-scale genome assembly of a Japanese chili pepper landrace, Capsicum annuum ... September 30, 2022 Kenta Shirasawa, Munetaka Hosokawa, Yasuo Yasui, Atsushi Toyoda, Sachiko Isobe
The generation of the first chromosome-level de-novo genome assembly and the development ... September 29, 2022 Guangtu Gao, Geoffrey C. Waldbieser, Ramey C. Youngblood, Dongyan Zhao, Michael R. Pietrak, Melissa S. Allen, Jason A. Stannard, John T. Buchanan, Roseanna L. Long, Melissa Milligan, Gary Burr, Katherine Mejía-Guerra, Moira J. Sheehan, Brian E. Scheffler, Caird E. Rexroad III, Brian C. Peterson, Yniv Palti

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