PMID- 38137484
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231225
IS  - 2227-9059 (Print)
IS  - 2227-9059 (Electronic)
IS  - 2227-9059 (Linking)
VI  - 11
IP  - 12
DP  - 2023 Dec 9
TI  - Analytic Validation of Optical Genome Mapping in Hematological Malignancies.
LID - 10.3390/biomedicines11123263 [doi]
LID - 3263
AB  - Structural variations (SVs) play a key role in the pathogenicity of hematological 
      malignancies. Standard-of-care (SOC) methods such as karyotyping and fluorescence 
      in situ hybridization (FISH), which have been employed globally for the past 
      three decades, have significant limitations in terms of resolution and the number 
      of recurrent aberrations that can be simultaneously assessed, respectively. 
      Next-generation sequencing (NGS)-based technologies are now widely used to detect 
      clinically significant sequence variants but are limited in their ability to 
      accurately detect SVs. Optical genome mapping (OGM) is an emerging technology 
      enabling the genome-wide detection of all classes of SVs at a significantly 
      higher resolution than karyotyping and FISH. OGM requires neither cultured cells 
      nor amplification of DNA, addressing the limitations of culture and amplification 
      biases. This study reports the clinical validation of OGM as a 
      laboratory-developed test (LDT) according to stringent regulatory (CAP/CLIA) 
      guidelines for genome-wide SV detection in different hematological malignancies. 
      In total, 60 cases with hematological malignancies (of various subtypes), 18 
      controls, and 2 cancer cell lines were used for this study. 
      Ultra-high-molecular-weight DNA was extracted from the samples, fluorescently 
      labeled, and run on the Bionano Saphyr system. A total of 215 datasets, 
      Inc.luding replicates, were generated, and analyzed successfully. Sample data 
      were then analyzed using either disease-specific or pan-cancer-specific BED files 
      to prioritize calls that are known to be diagnostically or prognostically 
      relevant. Sensitivity, specificity, and reproducibility were 100%, 100%, and 96%, 
      respectively. Following the validation, 14 cases and 10 controls were run and 
      analyzed using OGM at three outside laboratories showing reproducibility of 
      96.4%. OGM found more clinically relevant SVs compared to SOC testing due to its 
      ability to detect all classes of SVs at higher resolution. The results of this 
      validation study demonstrate the superiority of OGM over traditional SOC methods 
      for the detection of SVs for the accurate diagnosis of various hematological 
      malignancies.
FAU - Pang, Andy W C
AU  - Pang AWC
AD  - Bionano, San Diego, CA 92121, USA.
FAU - Kosco, Karena
AU  - Kosco K
AD  - Bionano Laboratories, San Diego, CA 92121, USA.
FAU - Sahajpal, Nikhil S
AU  - Sahajpal NS
AD  - Department of Pathology, Medical College of Georgia, Augusta University, Augusta, 
      GA 30912, USA.
FAU - Sridhar, Arthi
AU  - Sridhar A
AD  - Bionano Laboratories, San Diego, CA 92121, USA.
FAU - Hauenstein, Jen
AU  - Hauenstein J
AD  - Bionano, San Diego, CA 92121, USA.
FAU - Clifford, Benjamin
AU  - Clifford B
AD  - Bionano, San Diego, CA 92121, USA.
FAU - Estabrook, Joey
AU  - Estabrook J
AD  - Bionano, San Diego, CA 92121, USA.
FAU - Chitsazan, Alex D
AU  - Chitsazan AD
AD  - Bionano, San Diego, CA 92121, USA.
FAU - Sahoo, Trilochan
AU  - Sahoo T
AD  - Bionano Laboratories, San Diego, CA 92121, USA.
FAU - Iqbal, Anwar
AU  - Iqbal A
AD  - DNA Microarray CGH Laboratory, Department of Pathology, University of Rochester 
      Medical Center, Rochester, NY 14642, USA.
FAU - Kolhe, Ravindra
AU  - Kolhe R
AUID- ORCID: 0000-0002-8283-2403
AD  - Department of Pathology, Medical College of Georgia, Augusta University, Augusta, 
      GA 30912, USA.
FAU - Raca, Gordana
AU  - Raca G
AD  - Department of Pathology and Laboratory Medicine, Children's Hospital of Los 
      Angeles, Los Angeles, CA 90027, USA.
FAU - Hastie, Alex R
AU  - Hastie AR
AUID- ORCID: 0000-0001-5829-2649
AD  - Bionano, San Diego, CA 92121, USA.
AD  - Bionano Laboratories, San Diego, CA 92121, USA.
FAU - Chaubey, Alka
AU  - Chaubey A
AUID- ORCID: 0000-0002-0914-9237
AD  - Bionano, San Diego, CA 92121, USA.
AD  - Bionano Laboratories, San Diego, CA 92121, USA.
LA  - eng
GR  - This study was funded in part by Bionano./BioNano Genomics (United States)/
PT  - Journal Article
DEP - 20231209
PL  - Switzerland
TA  - Biomedicines
JT  - Biomedicines
JID - 101691304
PMC - PMC10741484
OTO - NOTNLM
OT  - copy-number variation (CNV)
OT  - optical genome mapping (OGM)
OT  - standard of care (SOC)
OT  - structural variation (SV)
COIS- Authors A.W.C.P., J.H., B.C., J.E., A.D.C., T.S., A.R.H., A.C. are employed by 
      the company Bionano Genomics Inc. Authors K.K. and A.S. were previously employed 
      by the company Bionano Genomics Inc. The author N.S.S. holds stock shares of 
      Bionano Genomics Inc. The author R.K. declares to have received funding in the 
      form of honoraria, travel funding and research support from Bionano Genomics Inc. 
      The remaining authors declare that the research was conducted in the absence of 
      any commercial or financial rela-tionships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/12/23 12:43
MHDA- 2023/12/23 12:44
PMCR- 2023/12/09
CRDT- 2023/12/23 01:10
PHST- 2023/10/27 00:00 [received]
PHST- 2023/11/23 00:00 [revised]
PHST- 2023/12/04 00:00 [accepted]
PHST- 2023/12/23 12:44 [medline]
PHST- 2023/12/23 12:43 [pubmed]
PHST- 2023/12/23 01:10 [entrez]
PHST- 2023/12/09 00:00 [pmc-release]
AID - biomedicines11123263 [pii]
AID - biomedicines-11-03263 [pii]
AID - 10.3390/biomedicines11123263 [doi]
PST - epublish
SO  - Biomedicines. 2023 Dec 9;11(12):3263. doi: 10.3390/biomedicines11123263.