Comparative Benchmarking of Optical Genome Mapping and Chromosomal Microarray Reveals High Technological Concordance in CNV Identification and Additional Structural Variant Refinement
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cohort Composition
2.2. Optical Genome Mapping
2.3. Data Analysis
3. Results
3.1. Concordance
3.2. Detection of Whole Chromosome Copy Gains and Losses and Copy Neutral Events
3.3. Microdeletion/Duplication Syndromes
3.4. OGM Resolves the Genomic Structure of CNVs
3.5. OGM Filtration Criteria Used to Select for Potential Pathogenic SVs
4. Discussion
4.1. Strengths and Limitations of OGM
4.2. CNV Size Discrepancies between CMA and OGM
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Method | Copy Number Variants | Total | |||
---|---|---|---|---|---|
Aneuploidy | Triploidy | Gain | Loss | ||
CMA | 5 | 2 | 21 | 33 | 61 |
OGM | 5 | 2 | 20 * | 33 | 60 |
Concordance | 100% | 100% | 95% | 100% | 98% |
Sample | CMA | FISH | OGM | Result |
---|---|---|---|---|
36 | arr[GRCh37] 2p25.3p25.2(36400_4801965)x3,10q26.12q26.3(123027554_135403394)x1 | der(10)t(2;10)(p25.2;q26.12) | ogm[GRCh37] t(2;10)(p25.2;q26.1)(4776157;123014483),2p25.3p25.2(15924_4746589)x3,10q26.12q26.3(123011875_135522591)x1 | OGM identified CNVs and translocation. |
41 | arr[GRCh37] 4q34.3q35.2(179412576_190896674)x3,9p24.3q31.1(209020_105724992)x3 | +der(9)t(4;9)(q34.3;q31.1) | ogm[GRCh37] t(4;9)(q34.3;q31.1)(179395177;105721182),4q34.3q35.2(179395177_191040751)x3,9p24.3q31.1(14556_105718660)x3, | OGM identified CNVs and translocation. |
44 | arr[GRCh37] 1q21.1q21.2(146531538_147726541)x3,9q34.3(139610281_141005513)x1,21q22.13q22.3(38319773_48091215)x3 | der(9)t(9;21)(q34.3;q22.13),(1q21.1)x3 | ogm[GRCh37] t(9;21)(q34.3;q22.13)(136684084;36948511),1q21.1q21.2(146057345_148928812)x3,9q34.3(136472755_138334464)x1,21q22.13q22.3(36948511_46697230)x3 | OGM identified CNVs and translocation. |
26 | arr[GRCh37] 2p11.2(85233220_85575202)x3 | der(2)ins(2)(p?15;p11.2p11.2) | ogm[GRCh37] ins(2;2)(p16.1;p11.2)(57631805;85217155_85572976) | OGM defined CNV insertion site. |
28 | arr[GRCh37] 3q29(197398764_197495350)x3 | der(17)ins(17;3)(p13.?3;q29q29) | ogm[GRCh37] ins(17;3)(p13.3;q29)(2155812/2276044;197344236_197495529) | OGM defined CNV insertion site. |
30 | arr[GRCh37] 6q14.1(77294196_77479434)x3 | der(X)ins(X;6)(Xq2?8;q14.1q14.1) | ogm[GRCh37] ins(X;6)(q28;q14.1)(152467195;77273466_77477943) | OGM defined CNV insertion site. |
31 | arr[GRCh37] 6q14.1(77294196_77479434)x3 | der(X)ins(X;6)(Xq2?8;q14.1q14.1) | ogm[GRCh37] ins(X;6)(q28;q14.1)(152467195;77273466_77477943) | OGM defined CNV insertion site. |
24 | arr[GRCh37] 1p36.22(11517159_11892978)x3 | (1p36.22)x3 | ogm[GRCh37] 1p36.22(11518058_11896987)x3 | Tandem duplication (defining orientation) |
38 | arr[GRCh37] 16p11.2(29657192_30192346)x3 | (16p11.2)x3 | ogm[GRCh37] 16p11.2(29463027_30202372)x3 | Tandem duplication (defining orientation) |
35 | arr[GRCh37] Xp21.3p21.2(28916857_29457146)x2 | (Xp21.3)x3 | ogm[GRCh37] Xp21.3(28912348_29459420)x2 | Tandem duplication (defining orientation) |
28 | arr[GRCh37] 6q12(76287632_77298392)x3 | (6q14.1)x3 | ogm[GRCh37] 6q12(76222934_77313055)x3 | Tandem duplication (defining orientation) |
40 | arr[GRCh37] 2p23.3(24633371_25529639)x3,2p23.3(25961533_26422725)x3 | (2p23.3)x3 | ogm[GRCh37] 2p23.3(24643804_25517100)x3,2q23.3(25943863_26441430)x3 | OGM identified both CNVs and characterized their structure. |
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Barseghyan, H.; Pang, A.W.C.; Clifford, B.; Serrano, M.A.; Chaubey, A.; Hastie, A.R. Comparative Benchmarking of Optical Genome Mapping and Chromosomal Microarray Reveals High Technological Concordance in CNV Identification and Additional Structural Variant Refinement. Genes 2023, 14, 1868. https://doi.org/10.3390/genes14101868
Barseghyan H, Pang AWC, Clifford B, Serrano MA, Chaubey A, Hastie AR. Comparative Benchmarking of Optical Genome Mapping and Chromosomal Microarray Reveals High Technological Concordance in CNV Identification and Additional Structural Variant Refinement. Genes. 2023; 14(10):1868. https://doi.org/10.3390/genes14101868
Chicago/Turabian StyleBarseghyan, Hayk, Andy Wing Chun Pang, Benjamin Clifford, Moises A. Serrano, Alka Chaubey, and Alex R. Hastie. 2023. "Comparative Benchmarking of Optical Genome Mapping and Chromosomal Microarray Reveals High Technological Concordance in CNV Identification and Additional Structural Variant Refinement" Genes 14, no. 10: 1868. https://doi.org/10.3390/genes14101868
APA StyleBarseghyan, H., Pang, A. W. C., Clifford, B., Serrano, M. A., Chaubey, A., & Hastie, A. R. (2023). Comparative Benchmarking of Optical Genome Mapping and Chromosomal Microarray Reveals High Technological Concordance in CNV Identification and Additional Structural Variant Refinement. Genes, 14(10), 1868. https://doi.org/10.3390/genes14101868