Progress Update for the Multisite Optical Genome Mapping Evaluation and Validation Study: Prenatal Applications DOI Creative Commons
Brynn Levy, Jie Liu, M. Anwar Iqbal

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 26, 2023

Abstract Optical genome mapping (OGM) is an emerging technology with great potential for prenatal diagnosis. OGM can identify and resolve all types of balanced unbalanced cytogenomic abnormalities in a single test, which are typically assessed by multiple standard care (SOC) methods including karyotyping, fluorescence situ hybridization chromosomal microarray. To assess OGM’s viability as alternative to conventional SOC testing, comprehensive clinical research study was conducted across sites, operators, instruments evaluate its accuracy utility. This report provides update the phase 2 results ongoing multisite evaluation validation evaluating applications. In 1, 123 cases were OGM, 2, 219 retrospective prospective have been evaluated. For 71% cases, at least two tests performed. The found that had overall 99.6% positive predictive value 100% when compared cytogenetic results. With standardized workflow, cost-effectiveness, high-resolution analysis, shows promise uses assay consolidate usually used

Language: Английский

Multisite Assessment of Optical Genome Mapping for Analysis of Structural Variants in Constitutional Postnatal Cases DOI Creative Commons
M. Anwar Iqbal,

Ulrich Broeckel,

Brynn Levy

et al.

Journal of Molecular Diagnostics, Journal Year: 2023, Volume and Issue: 25(3), P. 175 - 188

Published: Feb. 22, 2023

This study compares optical genome mapping (OGM) performed at multiple sites with current standard-of-care (SOC) methods used in clinical cytogenetics. included 50 negative controls and 359 samples from individuals (patients) suspected genetic conditions referred for cytogenetic testing. OGM was using the Saphyr system Bionano Access software version 1.7. Structural variants, including copy number aneuploidy, regions of homozygosity, were detected classified according to American College Medical Genetics Genomics guidelines. Repeated expansions FMR1 contractions facioscapulohumeral dystrophy 1 also analyzed. results compared SOC technical concordance, classification intrasite intersite reproducibility, ability provide additional, clinically relevant information. Across five testing sites, 98.8% (404/409) yielded successful data analysis interpretation. Overall, concordance detect previously reported 99.5% (399/401). The blinded variant agreement between 97.6% (364/373). Replicate 130 structural variations 100% concordant. On basis this demonstration analytic validity utility by multisite assessment, authors recommend technology as an alternative existing tests rapid detection diagnosis postnatal constitutional disorders.

Language: Английский

Citations

29
Clinical Cytogenetics: Current Practices and Beyond DOI
Mariam Mathew,

Melanie Babcock,

Ying‐Chen Claire Hou

et al.

The Journal of Applied Laboratory Medicine, Journal Year: 2024, Volume and Issue: 9(1), P. 61 - 75

Published: Jan. 1, 2024

Abstract Background Throughout history, the field of cytogenetics has witnessed significant changes due to constant evolution technologies used assess chromosome number and structure. Similar single nucleotide variant detection from Sanger sequencing next-generation sequencing, identification alterations progressed banding fluorescence in situ hybridization (FISH) chromosomal microarrays. More recently, emerging such as optical genome mapping have made noteworthy contributions clinical laboratory testing cytogenetics. Content In this review, we journey through some most pivotal discoveries that shaped development testing. We also explore current test offerings, their uses limitations, future directions technology advancements. Summary Cytogenetics methods, including targeted assessments like FISH, continue hold crucial roles cytogenetic These methods offer a rapid turnaround time, especially for conditions with known etiology involving recognized aberrations. Additionally, laboratories flexibility now employ higher-throughput methodologies enhance resolution cases greater complexity.

Language: Английский

Citations

6
Genome Mapping Nomenclature DOI
Sarah J. Moore, Jean McGowan‐Jordan, Adam C. Smith

et al.

Cytogenetic and Genome Research, Journal Year: 2023, Volume and Issue: 163(5-6), P. 236 - 246

Published: Jan. 1, 2023

<b><i>Background:</i></b> Genome Mapping Technologies (optical and electronic) use ultra-high molecular weight DNA to detect structural variation have application in constitutional genetic disorders, hematological neoplasms, solid tumors. mapping can balanced unbalanced variation, copy number changes, haplotypes. The technique is analogous chromosomal microarray analysis, although genome has the added benefit of being able ascertain nature more abnormalities a single assay than array, karyotyping, or FISH alone. <b><i>Key Messages:</i></b> This paper describes specific nomenclature for that be used by diagnostic research centers report their findings accurately. An international essential patient results understood different healthcare providers as well clear communication publications consistency databases. <b><i>Summary:</i></b> aneuploidy, changes. Standing Committee International System Human Cytogenomic Nomenclature (ISCN) recognised there was need encompasses range detected this technique. explains general principles giving ISCN examples types numerical rearrangements.

Language: Английский

Citations

13
Optical genome mapping for detection of chromosomal aberrations in prenatal diagnosis DOI Creative Commons
Qinxin Zhang, Yan Wang,

XU Yi-yun

et al.

Acta Obstetricia Et Gynecologica Scandinavica, Journal Year: 2023, Volume and Issue: 102(8), P. 1053 - 1062

Published: June 27, 2023

Abstract Introduction Chromosomal aberrations are the most important etiological factors for birth defects. Optical genome mapping is a novel cytogenetic tool detecting broad range of chromosomal in single assay, but relevant clinical feasibility studies optical prenatal diagnosis limited. Material and methods We retrospectively performed analysis amniotic fluid samples from 34 fetuses with various indications detected through standard‐of‐care technologies, including karyotyping, fluorescence situ hybridization, and/or microarray analysis. Results In total, we analyzed 46 samples, 5 aneuploidies, 10 large copy number variations, 27 microdeletions/microduplications, 2 translocations, 1 isochromosome, region homozygosity. Overall, 45 could be confirmed by our customized strategy. reached 97.8% concordant all blinded fashion. Compared widely used analysis, additionally determined relative orientation position repetitive segments seven cases duplications or triplications. The additional information provided will conducive to characterizing complex rearrangements allowing us propose mechanisms explain predict genetic recurrence risk. Conclusions Our study highlights that can provide comprehensive accurate on test, suggesting has potential become promising diagnosis.

Language: Английский

Citations

12
Prospective Investigation of Optical Genome Mapping for Prenatal Genetic Diagnosis DOI Creative Commons

Min Xie,

Zhao-Jing Zheng,

Ying Zhou

et al.

Clinical Chemistry, Journal Year: 2024, Volume and Issue: 70(6), P. 820 - 829

Published: March 22, 2024

Abstract Background Optical genome mapping (OGM) is a novel assay for detecting structural variants (SVs) and has been retrospectively evaluated its performance. However, prospective evaluation in prenatal diagnosis remains unreported. This study aimed to prospectively assess the technical concordance of OGM with standard care (SOC) testing diagnosis. Methods A cohort 204 pregnant women was enrolled this study. Amniotic fluid samples from these were subjected SOC testing, which included chromosomal microarray analysis (CMA) karyotyping (KT) parallel. The diagnostic yield evaluated, between assessed. Results successfully analyzed cultured amniocyte samples, even cell count as low 0.24 million. In total, 60 reportable SVs identified through combined 22 detected by all 3 techniques. OGM, CMA, KT 25% (51/204), 22.06% (45/204), 18.14% (37/204), respectively. highest (29.41%, 60/204) achieved when used together. demonstrated 95.56% CMA 75.68% Conclusions Our findings suggest that can be effectively applied using amniocytes exhibits high testing. use appears most promising outcomes.

Language: Английский

Citations

4
Pregnancy Loss: From Cytogenetics to Genomics DOI
Christina G. Tise, Kajal Verma, Ruth B. Lathi

et al.

Early pregnancy, Journal Year: 2025, Volume and Issue: unknown, P. 299 - 316

Published: April 16, 2025

Language: Английский

Citations

0
Optical Genome Mapping for Prenatal Diagnosis in Fetuses With Structural Anomalies DOI

XU Yi-yun,

Hao Chen, Qinxin Zhang

et al.

Prenatal Diagnosis, Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

ABSTRACT Objective To evaluate the clinical value of optical genome mapping (OGM) for prenatal diagnosis in fetuses with structural anomalies. Method OGM was performed prospectively 204 cases Detection rates were investigated. Subgroup analysis then conducted. Results Overall, pathogenic or likely (P/LP) chromosome aberrations identified 28 (13.7%) anomalies using OGM, including 12 numerical chromosomal abnormalities, 14 P/LP copy number variations (CNVs) and two balanced rearrangements. variation (SV) algorithm provided structure breakpoint information 17 SVs revealed six deletions, tandem direct duplications, one inverted duplication, paired duplication flanking a cryptic inversion three rearrangements (one benign breakpoints disrupting OMIM Morbid gene associated dominant inheritance disorders). The diagnostic yields cystic hygroma group multisystem malformation both significantly higher than those other groups (35.7% vs. 10.3%, adjusted p = 0.018; 31.3% 0.04). Conclusion Our study suggests that is reliable, comprehensive high‐resolution technology an acceptable turnaround time powerful method

Language: Английский

Citations

0
Optical Genome Mapping for Chromosomal Aberrations Detection—False-Negative Results and Contributing Factors DOI Creative Commons

XU Yi-yun,

Qinxin Zhang, Yan Wang

et al.

Diagnostics, Journal Year: 2024, Volume and Issue: 14(2), P. 165 - 165

Published: Jan. 11, 2024

Optical genome mapping (OGM) has been known as an all-in-one technology for chromosomal aberration detection. However, there are also aberrations beyond the detection range of OGM. This study aimed to report missed by OGM and analyze contributing factors. was performed taking both GRCh37 GRCh38 reference genomes. The results were analyzed in blinded fashion compared standard assays. Quality control (QC) metrics, sample types, genome, effective coverage classes locations then analyzed. In total, 154 clinically reported variations from 123 samples investigated. failed detect 10 (6.5%, 10/154) with assembly, including five copy number (CNVs), two submicroscopic balanced translocations, pericentric inversion one isochromosome (mosaicism). All passed pre-analytical analytical QC. With false-negative rate fell 4.5% (7/154). breakpoints CNVs, translocations inversions undetected located segmental duplication (SD) regions or no DLE-1 label. conclusion, besides centromeric breakpoints, structural (SVs) large repetitive sequences may be is recommended when performed. Our highlight necessity fully understanding limitation clinical practice.

Language: Английский

Citations

2
Combining optical genome mapping and RNA-seq for structural variants detection and interpretation in unsolved neurodevelopmental disorders DOI Creative Commons
Bing Xiao, Xiaomei Luo, Yi Liu

et al.

Genome Medicine, Journal Year: 2024, Volume and Issue: 16(1)

Published: Sept. 19, 2024

Language: Английский

Citations

2
Comparative Benchmarking of Optical Genome Mapping and Chromosomal Microarray Reveals High Technological Concordance in CNV Identification and Additional Structural Variant Refinement DOI Open Access
Hayk Barseghyan, Andy Wing Chun Pang, Ben Clifford

et al.

Genes, Journal Year: 2023, Volume and Issue: 14(10), P. 1868 - 1868

Published: Sept. 26, 2023

The recommended practice for individuals suspected of a genetic etiology disorders including unexplained developmental delay/intellectual disability (DD/ID), autism spectrum (ASD), and multiple congenital anomalies (MCA) involves testing workflow chromosomal microarray (CMA), Fragile-X testing, karyotype analysis, and/or sequencing-based gene panels. Since genomic imbalances are often found to be causative, CMA is as first tier many indications. Optical genome mapping (OGM) an emerging next generation cytogenomic technique that can detect not only copy number variants (CNVs), triploidy absence heterozygosity (AOH) like CMA, but also define the location duplications, other structural (SVs), balanced rearrangements repeat expansions/contractions. This study compares OGM clinically reported variants, some these samples have characterization by fluorescence in situ hybridization (FISH). was performed on IRB approved, de-identified specimens from 55 with abnormalities previously identified (61 abnormalities). SVs were filtered control database remove polymorphic against established list prioritize relevant findings before comparing FISH results. results showed 100% concordance pathogenic 98% concordant all pathogenic/likely pathogenic/variants uncertain significance (VUS), while providing additional insight into structure unable provide. demonstrates equivalent performance CNV AOH detection, enhanced its ability determine genome. work adds increasing body evidence analytical validity CMA. Moreover, identifies translocations, structures duplications complex CNVs intractable yielding clinical utility.

Language: Английский

Citations

6