scholarly journals Validation of a Customized Bioinformatics Pipeline for a Clinical Next-Generation Sequencing Test Targeting Solid Tumor–Associated Variants

2018 ◽  
Vol 20 (3) ◽  
pp. 355-365 ◽  
Author(s):  
Thomas Schneider ◽  
Geoffrey H. Smith ◽  
Michael R. Rossi ◽  
Charles E. Hill ◽  
Linsheng Zhang
Keyword(s):  
Next Generation Sequencing ◽  
Solid Tumor ◽  
Next Generation ◽  
Bioinformatics Pipeline ◽  
Generation Sequencing

scholarly journals Early solid tumor diagnosis through next-generation sequencing of cell-free DNA

2018 ◽  
Vol 12 (11) ◽  
pp. 1197-1201
Author(s):  
Demosthenes E Ziogas ◽  
Ioannis D Kyrochristos ◽  
Efstathios G Lykoudis ◽  
Dimitrios H Roukos
Keyword(s):  
Next Generation Sequencing ◽  
Solid Tumor ◽  
Tumor Diagnosis ◽  
Next Generation ◽  
Cell Free Dna ◽  
Free Dna ◽  
Generation Sequencing

scholarly journals Next generation sequencing of RB1gene for the molecular diagnosis of ethnic minority with retinoblastoma in Yunnan

2020 ◽  
Author(s):  
Huaiyu Gu ◽  
Zhen Zhang ◽  
Yi-shuang Xiao ◽  
Ru Shen ◽  
Hong-chao Jiang ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Next Generation Sequencing ◽  
Low Income ◽  
Eastern China ◽  
Low Income Countries ◽  
Next Generation ◽  
Single Nucleotide Variants ◽  
Bioinformatics Pipeline ◽  
Generation Sequencing

Abstract Background: Retinoblastoma is a rare intraocular malignancy and typically initiated by inactivating biallelic mutations of RB1 gene. Each year, ~8,000 children worldwide are diagnosed for retinoblastoma. In high-income countries, patient survival is over 95% while low-income countries is ~30%.If disease is diagnosed early and treated in centers specializing in retinoblastoma, the survival might exceed 95% and many eyes could be safely treated and support a lifetime of good vision. In China, approximate 1,100 newly diagnosed cases are expected annually and 28 hospitals covering 25 provinces established centers classified by expertise and resources for better treatment options and follow-up. Comparing with other province of eastern China, Yunnan province is remote geographically. This might result that healthcare staff have low awareness of the role of genetic testing in management and screening in families.Methods: The patients with retinoblastoma were selected in Yunnan. DNA from blood was used for targeted gene sequencing. Then, an in-house bioinformatics pipeline was done to detect both single nucleotide variants and small insertions/deletions. The pathogenic mutations were identified and further confirmed by conventional methods and cosegregation in families.Results: Using our approach, targeted next generation sequencing was used to detect the mutation of these 12 probands. Bioinformatic predictions showed that nine mutations were found in our study and four were novel pathogenic variants in these nine mutations.Conclusions: It’s the first report to describe RB1 mutations in Yunnan children with retinoblastoma. This study would improve role of genetic testing for management and family screening.

scholarly journals New Era for Next-Generation Sequencing in Japan

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 742 ◽  
Author(s):  
Masayuki Takeda ◽  
Kazuko Sakai ◽  
Takayuki Takahama ◽  
Kazuya Fukuoka ◽  
Kazuhiko Nakagawa ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Next Generation Sequencing ◽  
Solid Tumor ◽  
Recent Progress ◽  
Medical Curriculum ◽  
Next Generation ◽  
Multiple Cancer ◽  
New Era ◽  
Gene Panels ◽  
Generation Sequencing

Recent progress in understanding the molecular basis of cancer—including the discovery of cancer-associated genes such as oncogenes and tumor suppressor genes—has suggested that cancer can become a treatable disease. The identification of driver oncogenes such as EGFR, ALK, ROS1, BRAF and HER2 has already been successfully translated into clinical practice for individuals with solid tumor. Next-generation sequencing (NGS) technologies have led to the ability to test for multiple cancer-related genes at once with a small amount of cells and tissues. In Japan, several hospitals have started NGS-based mutational profiling screening in patients with solid tumor in order to guide patients to relevant clinical trials. The Ministry of Health, Labor, and Welfare of Japan has also approved several cancer gene panels for use in clinical practice. However, there is an urgent need to develop a medical curriculum of clinical variant interpretation and reporting. We review recent progress in the implementation of NGS in Japan.

Solid tumor profiling via next-generation sequencing to identify tumor-specific actionable variants.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 1539-1539
Author(s):  
Sara E. Patterson ◽  
Christopher S. Potter ◽  
Grace A. Stafford ◽  
Xing Yi Woo ◽  
Vanessa Spotlow ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Solid Tumor ◽  
Next Generation ◽  
Generation Sequencing ◽  
Actionable Variants ◽  
Tumor Profiling

scholarly journals Analytical validation and performance characteristics of a 48-gene next-generation sequencing panel for detecting potentially actionable genomic alterations in myeloid neoplasms

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0243683
Author(s):  
Sun Hee Rosenthal ◽  
Anna Gerasimova ◽  
Charles Ma ◽  
Hai-Rong Li ◽  
Andrew Grupe ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Myeloproliferative Neoplasms ◽  
Simultaneous Detection ◽  
Molecular Testing ◽  
Next Generation ◽  
Analytical Validation ◽  
Bioinformatics Pipeline ◽  
Myeloid Neoplasms ◽  
Clinically Significant ◽  
Generation Sequencing

Identification of genomic mutations by molecular testing plays an important role in diagnosis, prognosis, and treatment of myeloid neoplasms. Next-generation sequencing (NGS) is an efficient method for simultaneous detection of clinically significant genomic mutations with high sensitivity. Various NGS based in-house developed and commercial myeloid neoplasm panels have been integrated into routine clinical practice. However, some genes frequently mutated in myeloid malignancies are particularly difficult to sequence with NGS panels (e.g., CEBPA, CARL, and FLT3). We report development and validation of a 48-gene NGS panel that includes genes that are technically challenging for molecular profiling of myeloid neoplasms including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and myeloproliferative neoplasms (MPN). Target regions were captured by hybridization with complementary biotinylated DNA baits, and NGS was performed on an Illumina NextSeq500 instrument. A bioinformatics pipeline that was developed in-house was used to detect single nucleotide variations (SNVs), insertions/deletions (indels), and FLT3 internal tandem duplications (FLT3-ITD). An analytical validation study was performed on 184 unique specimens for variants with allele frequencies ≥5%. Variants identified by the 48-gene panel were compared to those identified by a 35-gene hematologic neoplasms panel using an additional 137 unique specimens. The developed assay was applied to a large cohort (n = 2,053) of patients with suspected myeloid neoplasms. Analytical validation yielded 99.6% sensitivity (95% CI: 98.9–99.9%) and 100% specificity (95% CI: 100%). Concordance of variants detected by the 2 tested panels was 100%. Among patients with suspected myeloid neoplasms (n = 2,053), 54.5% patients harbored at least one clinically significant mutation: 77% in AML patients, 48% in MDS, and 45% in MPN. Together, these findings demonstrate that the assay can identify mutations associated with diagnosis, prognosis, and treatment options of myeloid neoplasms even in technically challenging genes.

Identifying large indels in targeted next generation sequencing assays for myeloid neoplasms: a cautionary tale of the ZRSR1 pseudogene

2017 ◽  
Vol 70 (12) ◽  
pp. 1069-1073 ◽  
Author(s):  
Isaac KS Ng ◽  
Christopher Ng ◽  
Jia Jin Low ◽  
Lily Chiu ◽  
Elaine Seah ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Clinical Diagnostics ◽  
Great Promise ◽  
Next Generation ◽  
Bioinformatics Pipeline ◽  
Targeted Next Generation Sequencing ◽  
Molecular Features ◽  
Myeloid Neoplasms ◽  
Large Indels ◽  
Generation Sequencing

Targeted next generation sequencing platforms have been increasingly utilised for identification of novel mutations in myeloid neoplasms, such as acute myeloid leukaemia (AML), and hold great promise for use in routine clinical diagnostics. In this study, we evaluated the utility of an open source variant caller in detecting large indels in a targeted sequencing of AML samples. While we found that this bioinformatics pipeline has the potential to accurately capture large indels (>20 bp) in patient samples, we highlighted the pitfall of a confounding ZRSR1 pseudogene that led to an erroneous ZRSR2 variant call. We further discuss possible clinical implications of the ZRSR1 pseudogene in myeloid neoplasms based on its molecular features. Knowledge of the confounding ZRSR1 pseudogene in ZRSR2 sequencing assays could be particularly important in AML diagnostics because the detection of ZRSR2 in AML patients is highly specific for an s-AML diagnosis.

scholarly journals A bioinformatics pipeline for rare genetic diseases in South African patients

2019 ◽  
Vol 115 (3/4) ◽  
Author(s):  
Maryke Schoonen ◽  
Albertus S. Seyffert ◽  
Francois H. van Der Westhuizen ◽  
Izelle Smuts
Keyword(s):  
South Africa ◽  
Next Generation Sequencing ◽  
South African ◽  
Rare Diseases ◽  
Next Generation Sequencing Data ◽  
Common Disease ◽  
Next Generation ◽  
Sequencing Data ◽  
Bioinformatics Pipeline ◽  
Generation Sequencing

The research fields of bioinformatics and computational biology are growing rapidly in South Africa. Bioinformatics pipelines play an integral part in handling sequencing data, which are used to investigate the aetiology of common and rare diseases. Bioinformatics platforms for common disease aetiology are well supported and continuously being developed in South Africa. However, the same is not the case for rare diseases aetiology research. Investigations into the latter rely on international cloud-based tools for data analyses and ultimately confirmation of a genetic disease. However, these tools are not necessarily optimised for ethnically diverse population groups. We present an in-house developed bioinformatics pipeline to enable researchers to annotate and filter variants in either exome or amplicon next-generation sequencing data. This pipeline was developed using next-generation sequencing data of a predominantly African cohort of patients diagnosed with rare disease. Significance: We demonstrate the feasibility of in-country development of ethnicity-sensitive, automated bioinformatics pipelines using free software in a South African context. We provide a roadmap for development of similarly ethnicity-sensitive bioinformatics pipelines.

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