scholarly journals The clinical value of metagenomic next-generation sequencing in the microbiological diagnosis of skin and soft tissue infections

2020 ◽  
Vol 100 ◽  
pp. 414-420 ◽  
Author(s):  
Qingqing Wang ◽  
Qing Miao ◽  
Jue Pan ◽  
Wenting Jin ◽  
Yuyan Ma ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Soft Tissue ◽  
Soft Tissue Infections ◽  
Microbiological Diagnosis ◽  
Next Generation ◽  
Clinical Value ◽  
Generation Sequencing

Clinical value of Next Generation Sequencing in Chinese pediatric soft tissue sarcoma: A multicenter data.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e22005-e22005
Author(s):  
Suying Lu ◽  
Feifei Sun ◽  
Xiuli Yuan ◽  
Junting Huang ◽  
Juan Wang ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Genomic Analysis ◽  
Parp Inhibition ◽  
Cancer Center ◽  
Next Generation ◽  
Clinical Value ◽  
Mesenchymal Tumors ◽  
Generation Sequencing

e22005 Background: To uncover the genomic characteristics as well as to, within the scope of pediatric soft tissue sarcoma (psts), assess the clinical value of Next Generation Sequencing (NGS), we present the first report of genomic profiles in Chinese psts. Methods: Tumor tissue, as well as peripheral blood from 41 psts patients, were collected in Sun Yat-Sen University Cancer Center, Shenzhen Children's Hospital and Nanfang Hospital. Samples were sequenced in a CLIA/CAP-accredited laboratory with a targeted NGS panel (Onco PanScan plus; GenetronHealth.inc) consisted of all exons of 831 cancer-related genes and mRNA of 395 genes. Bioinformatics analysis was conducted using a build-in computational pipeline. Results: A total of 41 samples consisted of five major histology types including rhabdomyosarcoma (RMS) (n = 11), fibrosarcoma (n = 4), Ewing's sarcoma (n = 4), INI1-deficient mesenchymal tumor (n = 4), and other mesenchymal tumors (n = 18). All patients were with doubtful diagnosis,advanced, relapsed, or refractory sarcoma, of which 85% samples were from initial diagnoses. In totally, we identified 116 somatic aberrations and 4 pathogenic or likely pathogenic germline mutations, with a median tumor mutational burden of 0.47/Mb (0–6.57). Genomic analysis revealed frequent alterations in TP53 (10%), NTRK fusion (10%), PAX3/7 fusion (8%), and ARID1A (7%). ARID1A (18% vs. 0%) and TP53 (18% vs. 3%) mutations were found with higher frequency compared with pediatric RMS data in a previous study (Jack et al 2014). ARID1A mutation was only reported in a RMS case report (Cramer et al 2017). Furthermore, the mutation of ARID1A potentially match PARP inhibitors, which may provide more therapeutic options. In addition, NGS aided pathologic diagnosis in 63% (26/41) patients. The proportion of confirmed diagnosis, differential diagnosis, and the excluded diagnosis was 41.5%, 12.2%, and 9.7%, respectively. Druggable alterations were detected in 39% patients (Table). Four patients received the treatment recommended by genetic testing, three of them with NTRK fusion were recruited in a matched clinical trial could be evaluated and showed partial remission upon Larotrectinib. Conclusions: We discovered ARID1A mutations, which potentially sensitive to PARP-inhibition, were at a higher incidence in Chinese RMS. This study demonstrated the value of NGS test in guiding the clinical practice of psts in Chinese population. [Table: see text]

scholarly journals Clinical Application of Next-Generation Sequencing of Plasma Cell-Free DNA for Genotyping Untreated Advanced Non-Small Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2707
Author(s):  
Maria Gabriela O. Fernandes ◽  
Natália Cruz-Martins ◽  
Conceição Souto Moura ◽  
Susana Guimarães ◽  
Joana Pereira Reis ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Next Generation Sequencing ◽  
Clinical Outcomes ◽  
Test Performance ◽  
Molecular Diagnostic ◽  
Test Accuracy ◽  
Newly Diagnosed ◽  
Next Generation ◽  
Clinical Value ◽  
Generation Sequencing

Background: Analysis of circulating tumor DNA (ctDNA) has remarkable potential as a non-invasive lung cancer molecular diagnostic method. This prospective study addressed the clinical value of a targeted-gene amplicon-based plasma next-generation sequencing (NGS) assay to detect actionable mutations in ctDNA in patients with newly diagnosed advanced lung adenocarcinoma. Methods: ctDNA test performance and concordance with tissue NGS were determined, and the correlation between ctDNA findings, clinical features, and clinical outcomes was evaluated in 115 patients with paired plasma and tissue samples. Results: Targeted-gene NGS-based ctDNA and NGS-based tissue analysis detected 54 and 63 genomic alterations, respectively; 11 patients presented co-mutations, totalizing 66 hotspot mutations detected, 51 on both tissue and plasma, 12 exclusively on tissue, and 3 exclusively on plasma. NGS-based ctDNA revealed a diagnostic performance with 81.0% sensitivity, 95.3% specificity, 94.4% PPV, 83.6% NPV, test accuracy of 88.2%, and Cohen’s Kappa 0.764. PFS and OS assessed by both assays did not significantly differ. Detection of ctDNA alterations was statistically associated with metastatic disease (p = 0.013), extra-thoracic metastasis (p = 0.004) and the number of organs involved (p = 0.010). Conclusions: This study highlights the potential use of ctDNA for mutation detection in newly diagnosed NSCLC patients due to its high accuracy and correlation with clinical outcomes.

scholarly journals Simultaneous Detection of Pathogens and Tumors in Patients With Suspected Infections by Next-Generation Sequencing

2021 ◽  
Author(s):  
Jiachun Su ◽  
Xu Han ◽  
Xiaogang Xu ◽  
Wenchao Ding ◽  
Ming Li ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Chromosomal Abnormalities ◽  
Malignant Tumors ◽  
Simultaneous Detection ◽  
Prior History ◽  
Next Generation ◽  
Clinical Value ◽  
Microbiological Testing ◽  
Number Variation ◽  
Generation Sequencing

Abstract Background: Differential diagnosis of patients with suspected infections is particularly difficult, but necessary for prompt diagnosis and rational use of antibiotics. A substantial proportion of these patients have non-infectious diseases that include malignant tumors. Metagenomic next-generation sequencing (mNGS) technologies are used with increasing frequency to aid clinical diagnosis of patients with suspected infections. Methods: Based upon mNGS technologies and chromosomal copy number variation (CNV) analysis on abundant human genome, a new workflow named Onco-mNGS was established to simultaneously detect pathogens and malignant tumors in patients with suspected infections. Results: Of 140 patients screened by Onco-mNGS testing at four hospitals in Shanghai, 115 patients were diagnosed with infections; 17 had obvious abnormal CNV signals indicating malignant tumors that were confirmed clinically. The sensitivity and specificity of mNGS testing for diagnosis of a clinically relevant infection was 53.0% (61/115) and 60% (15/25), respectively, vs 20.9% (24/115) and 96.0% (24/25), respectively, for conventional microbiological testing (both P<0.01). Klebsiella pneumoniae was the most common pathogen detected by mNGS, followed by E. coli and viruses. The chromosomal abnormalities of the 17 cases included genome-wide variations and local variations of a certain chromosome. Five of 17 patients had a final confirmed with malignant tumors, including three lung adenocarcinomas and two hematological tumors; one patient was highly suspected to have lymphoma; and 11 patients had a prior history of malignant tumor.Conclusions: This preliminary study demonstrates the feasibility and clinical value of using Onco-mNGS to simultaneously search for potential pathogens and malignant tumors in patients with suspected infections.

scholarly journals What Does 16S rRNA Gene-Targeted Next Generation Sequencing Contribute to the Study of Infective Endocarditis in Heart-Valve Tissue?

Pathogens ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 34
Author(s):  
Paula Santibáñez ◽  
Concepción García-García ◽  
Aránzazu Portillo ◽  
Sonia Santibáñez ◽  
Lara García-Álvarez ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Infective Endocarditis ◽  
16S Rrna ◽  
16S Rrna Gene ◽  
Heart Valve ◽  
Rrna Gene ◽  
Microbiological Diagnosis ◽  
Next Generation ◽  
Targeted Ngs ◽  
Generation Sequencing

Infective endocarditis (IE) is a severe and life-threatening disease. Identification of infectious etiology is essential for establishing the appropriate antimicrobial treatment and decreasing mortality. The aim of this study was to explore the potential utility of metataxonomics for improving microbiological diagnosis of IE. Here, next-generation sequencing (NGS) of the V3–V4 region of the 16S rRNA gene was performed in 27 heart valve tissues (18 natives, 5 intravascular devices, and 4 prosthetics) from 27 patients diagnosed with IE (4 of them with negative blood cultures). Metataxonomics matched with conventional diagnostic techniques in 24/27 cases (88.9%). The same bacterial family was assigned to 24 cases; the same genus, to 23 cases; and the same species, to 13 cases. In 22 of them, the etiological agent was represented by percentages > 99% of the reads and in two cases, by ~70%. Staphylococcus aureus was detected in a previously microbiological undiagnosed patient. Thus, microbiological diagnosis with 16S rRNA gene targeted-NGS was possible in one more sample than using traditional techniques. The remaining two patients showed no coincidence between traditional and 16S rRNA gene-targeted NGS microbiological diagnoses. In addition, 16S rRNA gene-targeted NGS allowed us to suggest coinfections that were supported by clinical data in one patient, and minority records also verified mixed infections in three cases. In our series, metataxonomics was valid for the identification of the causative agents, although more studies are needed before implementation of 16S rRNA gene-targeted NGS for the diagnosis of IE.

scholarly journals Assessment of the Application and Clinical Value of Next-Generation Sequencing for the Diagnosis of Inherited Thrombocytopenia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4993-4993
Author(s):  
Miao Jiang ◽  
Qi Wang ◽  
Yiming Zhao ◽  
Ziqiang Yu ◽  
Suning Chen ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Conflicts Of Interest ◽  
Gene Sequencing ◽  
Hereditary Diseases ◽  
Next Generation ◽  
Clinical Value ◽  
Sequencing Platform ◽  
Pathogenic Variants ◽  
Inherited Thrombocytopenia ◽  
Generation Sequencing

Abstract Inherited thrombocytopenia is a group of hereditary diseases with a reduction in platelet count as the main clinical manifestation. Clinically, there is an urgent need for a convenient and rapid diagnosis method. We introduced a high-throughput next-generation sequencing (NGS) platform into the routine diagnosis of patients with unexplained thrombocytopenia and analyzed the gene sequencing results to evaluate the value of NGS technology in the screening and diagnosis of inherited thrombocytopenia. From a cohort of 182 patients with thrombocytopenia, we screened 78 patients with hereditary features. For the blood samples of these 78 patients, a gene sequencing platform for hemorrhagic and thrombotic diseases comprising 89 genes was used to perform gene detection using NGS technology. When we combined the screening results with clinical features and other findings, 23 of 78 patients (29.5%) were diagnosed with inherited thrombocytopenia. In addition, 29 pathogenic variants, including 11 previously unreported variants, were identified in these patients. In summary, NGS could play more important role in the molecular pathology diagnosis of inherited thrombocytopenia. Through the use of this detection platform, we expect to establish a more effective diagnostic approach to such disorders. Disclosures No relevant conflicts of interest to declare.

Molecular profiling of soft tissue sarcomas using next-generation sequencing: a pilot study toward precision therapeutics

2014 ◽  
Vol 45 (8) ◽  
pp. 1563-1571 ◽  
Author(s):  
George Jour ◽  
John D. Scarborough ◽  
Robin L. Jones ◽  
Elizabeth Loggers ◽  
Seth M. Pollack ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Pilot Study ◽  
Soft Tissue ◽  
Soft Tissue Sarcomas ◽  
Molecular Profiling ◽  
Next Generation ◽  
Generation Sequencing ◽  
Precision Therapeutics

Clinical benefit of next generation sequencing in soft tissue and bone sarcoma: Rush University Medical Center’s experience.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e22552-e22552
Author(s):  
Mia C. Weiss ◽  
Alan Blank ◽  
Steven Gitelis ◽  
Mary J. Fidler ◽  
Marta Batus
Keyword(s):  
Overall Survival ◽  
Next Generation Sequencing ◽  
Soft Tissue ◽  
Clinical Decision Making ◽  
Soft Tissue Sarcomas ◽  
Bone Sarcoma ◽  
Next Generation ◽  
Undifferentiated Sarcoma ◽  
The Impact ◽  
Generation Sequencing

e22552 Background: The overall survival for metastatic sarcoma has remained at only 18-20%. In the era of next generation sequencing (NGS), much research is ongoing on identifying optimal treatments. The MULTISARC trial aims to determine if NGS can lead to improved overall survival by randomizing patients with metastatic STS to receive NGS (followed by possible NGS-guided therapy) or not. We present our center’s experience with NGS in sarcomas patients. Methods: Patients with soft tissue and bone sarcomas at Rush that had the Foundation Medicine assay sent on tumor samples between August 2017 and August 2018 were analyzed retrospectively. The impact of NGS on clinical decision making was determined based on patients being prescribed off-label FDA-approved therapy targeting identified mutation. Results: Thirty-four patients with bone/soft tissue sarcomas that had NGS sent on specimens were identified. Median age at diagnosis: 43 (18-78 years); 18 males, 16 females. Histologic subtypes: synovial sarcoma, myxofibrosarcoma, leiomyosarcoma, chondrosarcoma, sclerosing epitheloid fibrosarcoma, PEcoma, pleomorphic undifferentiated sarcoma, MPNST, liposarcoma- well and de-differentiated, angiosarcoma, osteosarcoma. 16/34 patients had targetable mutations with approved therapies in tumor types other than sarcoma. Four of these patients had therapy changed based on NGS results, 1 patient with metastatic chondrosarcoma (PTEN mutation, everolimus added), 1 patient with metastatic liposarcoma (CDK4 mutation, palbociclib added), 1 patient with metastatic osteosarcoma (CCD1/CDK4 and a PDGFRA mutation for which palbociclib followed by imatinib was added), and 1 patient with metastatic pleomorphic undifferentiated sarcoma (CDK4 mutation, palbociclib added). Targetable mutations for which clinical trials are available were identified in 25/34 (73%) of the cases. Conclusions: NGS was readily able to identify actionable mutations in close to 50% of patients with clinical trial opportunities in close to 75%. Four patients had therapy changed as a result of NGS testing. Although our study size is small, our data show potential for the use of genomic profiling to identify actionable targets, tailor therapy, and hopefully improve outcomes. [Table: see text]

The Value of Next-Generation Sequencing in the Screening and Evaluation of Hematologic Neoplasms in Clinical Practice

2019 ◽  
Vol 153 (5) ◽  
pp. 639-645 ◽  
Author(s):  
Victoria Northrup ◽  
Allison Maybank ◽  
Nancy Carson ◽  
Tarek Rahmeh
Keyword(s):  
Next Generation Sequencing ◽  
Next Generation ◽  
Hematologic Neoplasms ◽  
Clinical Value ◽  
Variants Of Unknown Significance ◽  
Myeloid Neoplasms ◽  
Unknown Significance ◽  
Conventional Cytogenetics ◽  
Generation Sequencing

Abstract Objectives The implementation of next-generation sequencing (NGS) in routine clinical hematology practice remains limited. We evaluate the clinical value of NGS in the screening, diagnosis, and follow-up in hematologic neoplasms. Methods A targeted NGS panel was used to assess a total of 178 patients for questionable or previously diagnosed myeloid neoplasms. Results Gene variants were identified in 53% of patients. Novel variants were identified in 29% of patients and variants of unknown significance in 34%. Bone marrow samples yielded a higher number of variants than in peripheral blood. NGS is a more sensitive test than conventional cytogenetics. In several cases, NGS played a key role in the screening, diagnostics, prognostic stratification, and the clinical follow-up of a wide variety of myeloid neoplasms. Conclusions NGS is an effective tool in the evaluation of suspected and confirmed hematologic neoplasms and could become part of the routine workup of patients.

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