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A comparative study of curated contents by knowledge-based curation system in cancer clinical sequencing

机译:基于知识的策展系统在癌症临床测序中策展内容的比较研究

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摘要

Medical oncologists are challenged to personalize medicine with scientific evidence, drug approvals, and treatment guidelines based on sequencing of clinical samples using next generation sequencer (NGS). Knowledge-based curation systems have the potential to help address this challenge. We report here the results of examining the level of evidence regarding treatment approval and clinical trials between recommendations made by Watson for Genomics (WfG), QIAGEN Clinical Insight Interpret (QCII), and Oncomine knowledge-based reporter (OKR). The tumor samples obtained from the solid cancer patients between May to June 2018 at Kindai University Hospital. The formalin-fixed paraffin-embedded tumor samples (n = 31) were sequenced using Oncomine Comprehensive Assay v3. Variants including copy number alteration and gene fusions identified by the Ion reporter software were used commonly on three curation systems. Curation process of data were provided for 25 solid cancers using three curation systems independently. Concordance and distribution of curated evidence levels of variants were analyzed. As a result of sequencing analysis, nonsynonymous mutation (n = 58), gene fusion (n = 2) or copy number variants (n = 12) were detected in 25 cases, and subsequently subjected to knowledge-based curation systems (WfG, OKR, and QCII). The number of curated information in any systems was 51/72 variants. Concordance of evidence levels was 65.3% between WfG and OKR, 56.9% between WfG and QCII, and 66.7% between OKR and QCII. WfG provided great number of clinical trials for the variants. The annotation of resistance information was also observed. Larger differences were observed in clinical trial matching which could be due to differences in the filtering process among three curation systems. This study demonstrates knowledge-based curation systems (WfG, OKR, and QCII) could be helpful tool for solid cancer treatment decision making. Difference in non-concordant evidence levels was observed between three curation systems, especially in the information of clinical trials. This point will be improved by standardized filtering procedure and enriched database of clinical trials in Japan.
机译:肿瘤医学专家面临着使用下一代测序仪(NGS)对临床样品进行测序的科学证据,药物批准和治疗指南,以个性化医学的挑战。基于知识的策展系统有潜力帮助应对这一挑战。我们在这里报告了有关沃森基因组学(WfG),QIAGEN Clinical Insight Interpret(QCII)和基于Oncomine知识的记者(OKR)提出的建议之间有关治疗批准和临床试验的证据水平的检验结果。 2018年5月至2018年6月在金代大学医院从实体癌症患者获得的肿瘤样本。使用Oncomine综合检测v3对福尔马林固定石蜡包埋的肿瘤样品(n = 31)进行测序。由三个离子系统共同使用的变体包括拷贝数变化和通过离子报告软件鉴定的基因融合。使用三种管理系统分别提供了25种实体癌的数据处理过程。分析了变体精选证据水平的一致性和分布。测序分析的结果是,在25例中检测到非同义突变(n = 58),基因融合(n = 2)或拷贝数变异(n = 12),随后接受了基于知识的管理系统(WfG,OKR和QCII)。在任何系统中,精选信息的数量均为51/72。 WfG和OKR之间的证据水平一致性为65.3%,WfG和QCII之间的证据水平一致性为56.9%,OKR和QCII之间的证据水平一致性为66.7%。 WfG为这些变体提供了大量的临床试验。还观察到了电阻信息的注释。在临床试验匹配中观察到较大的差异,这可能是由于三个策展系统之间的过滤过程不同所致。这项研究表明,基于知识的管理系统(WfG,OKR和QCII)可能是制定实体癌症治疗决策的有用工具。在三个策展系统之间,尤其是在临床试验信息中,观察到不一致的证据水平存在差异。通过标准化过滤程序和丰富的日本临床试验数据库,这一点将得到改善。

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