Orthogonal NGS for High Throughput Clinical Diagnostics

Chennagiri, Niru; White, Eric J.; Frieden, Alexander; Lopez, Edgardo; Lieber, Daniel S.; Nikiforov, Anastasia; Ross, Tristen; Batorsky, Rebecca; Hansen, Sherry; Lip, Va; Luquette, Lovelace J.; Mauceli, Evan; Margulies, David M.; Milos, Patrice M.; Napolitano, Nichole M.; Nizzari, Marcia M.; Yu, Timothy W.; Thompson, John F.

doi:10.1038/srep24650

Cited by 14 publications

(13 citation statements)

References 30 publications

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“…Exome sequencing was performed by Claritas Genomics using an orthogonal next-generation sequencing platform approach 6 , combining Illumina Trusight One sequencing (targeting 11.9 Mb of human disease-relevant genes) on the MiSeq with Proton Ampliseq whole exome sequencing. On the MiSeq platform, 29.5 million total reads were generated (mean read length of 150 bp) for a mean coverage of 185x.…”

Section: Methodsmentioning

confidence: 99%

Increased Survival and Partly Preserved Cognition in a Patient WithACO2-Related Disease Secondary to a Novel Variant

et al. 2017

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ACO2 encodes aconitase 2, catalyzing the second step of the tricarboxylic acid. To date, there are only six reported families with five unique ACO2 mutations. Affected individuals can develop intellectual disability (ID), epilepsy, brain atrophy, hypotonia, ataxia, optic atrophy, and retinal degeneration. Here, we report an 18-year-old boy with a novel ACO2 variant discovered on whole-exome sequencing. He presented with childhood onset ataxia, impaired self-help skills comparable to severe-profound ID, intractable epilepsy, cerebellar atrophy, peripheral neuropathy, optic atrophy, and pigmentary retinopathy. His variant is the sixth unique ACO2 mutation. In addition, compared to mild cases (isolated optic atrophy) and severe cases (infantile death), our patient may be moderately affected, evident by increased survival and some preserved cognition (ability to speak full sentences and follow commands), which is a novel presentation. This case expands the disease spectrum to include increased survival with partly spared cognition.

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Section: Methodsmentioning

confidence: 99%

Increased Survival and Partly Preserved Cognition in a Patient WithACO2-Related Disease Secondary to a Novel Variant

et al. 2017

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“…NGS is a high-throughput method that can detect numerous genetic variations, such as single nucleotide variants, insertions and deletions, copy number variations, and gene fusions over larger genomic regions. It is also noted for its high sensitivity and specificity [12]. Consequently, NGS may be a good tool for guiding the treatment of NSCLC.…”

Section: Introductionmentioning

confidence: 99%

The Value of Next-Generation Sequencing for Treatment in Non-Small Cell Lung Cancer Patients: The Observational, Real-World Evidence in China

Zhang

Shen

Zhou

et al. 2020

BioMed Research International

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Background. Great success has been made in the targeting therapy of advanced non-small cell lung cancer (NSCLC). Nowadays, next generation sequencing (NGS) is acquirable and affordable in developed area of China. Using this feasible and accurate method of detecting therapeutic genes would help to select optimal treatments to extend patients survival. Here, we identified somatic mutations by NGS and analyzed the value for treatment of NSCLC in a real-world clinical setting. Methods. NGS was carried out on biopsy samples obtained from 66 advanced unresectable NSCLC patients who had not received any treatment. 23 patients received liquid biopsy after failure of first-line targeted treatment. The mutation profiling as well as associations between mutations and clinicopathological characters was analyzed. The study also assessed the values of NGS for choosing treatment options and predicting prognosis in NSCLC patients. Results. 152 somatic mutations were identified in 45 (68.18%) tissue samples. The most frequently mutated genes were EGFR (42.42%), TP53 (31.82%) and KRAS (15.15%). Specifically, the most frequent EGFR mutation subtypes were exon 19 deletion (60.71%) and L858R in exon 21 (46.43%). 83.33% mutated patients received targeted therapy. Among the adenocarcinoma cases, patients with EGFR exon 19 deletion mutation have longer overall survival (OS) than the wide-type (36.0 months versus 19.0 months p=0.046). In addition, in the smoking group, patients with EGFR exon 19 deletion mutation tended to have longer OS (38.0 months versus 16.5 months p<0.01). After the failure of first-line targeted therapy, 23 EGFR mutated patients received liquid biopsy, and the positive rate of T790M mutation in EGFR exon 20 was 47.83%. T790M positive patients have longer progression-free survival (PFS) than the others (15 months versus 9.5 months p=0.025). Conclusions. The observational study from real-world demonstrated that using NGS in routine clinical detection may be useful in guiding the therapy decisions and benefit more Chinese NSCLC patients.

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“…The relatively high raw base-calling error rate and variable performance of next generation sequencing (NGS) platforms is well recognized. 30 Our study highlights the added value of a dual platform approach employing complementary NGS protocols 31 to improve variant yield and reduce false-negative calls.…”

Section: Discussionmentioning

confidence: 90%

Charcot–Marie–Tooth disease type 2G redefined by a novel mutation in LRSAM1

Peeters

Palaima

Pelayo‐Negro

et al. 2016

Annals of Neurology

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Our findings demonstrate that the isolated genetic entity CMT2G is caused by a missense mutation in LRSAM1 and should be reclassified as CMT2P. MRI of lower-limb musculature can be used to detect minimal signs of the disease. Transcriptome analysis of patients' cells highlights novel molecular players associated with LRSAM1 dysfunction, and reveals pathways and therapeutic targets shared with amyotrophic lateral sclerosis and Alzheimer disease. Ann Neurol 2016;80:823-833.

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Orthogonal NGS for High Throughput Clinical Diagnostics

Cited by 14 publications

References 30 publications

Increased Survival and Partly Preserved Cognition in a Patient WithACO2-Related Disease Secondary to a Novel Variant

Increased Survival and Partly Preserved Cognition in a Patient WithACO2-Related Disease Secondary to a Novel Variant

The Value of Next-Generation Sequencing for Treatment in Non-Small Cell Lung Cancer Patients: The Observational, Real-World Evidence in China

Charcot–Marie–Tooth disease type 2G redefined by a novel mutation in LRSAM1

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