通过高效的 NGS 数据过滤系统优先选择具有临床意义的肺癌体细胞突变进行靶向治疗

Jinlian Wang, Hui Li, Hongfang Liu
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引用次数: 0

摘要

在肺癌治疗领域,遗传异质性带来了严峻的挑战,精准肿瘤学需要一种精确的方法来识别和分层分类具有临床意义的体细胞突变。目前的下一代测序(NGS)数据筛选管道虽然利用了各种外部数据库进行突变筛选,但往往缺乏所需的全面整合性和灵活性,无法跟上临床数据不断发展的步伐。我们的研究介绍了一种先进的 NGS 数据筛选系统,它不仅能聚合不同的数据源,还能有效协同,包括基因变异、基因功能、临床证据和大量文献。该系统的独特之处在于它采用了一种独特的算法,可进行严格的多层过滤。这样就能从大型数据集中有效地优先筛选出 420 个基因和 1,193 个变异体,尤其是 80 个显示出高度临床可操作性的变异体。这些变异与 FDA 批准、NCCN 指南和经过全面审查的文献相一致,从而为肿瘤学家的靶向治疗决策提供了精良的武器。我们系统的创新之处在于其动态整合框架及其算法,该算法量身定制,强调临床实用性和可操作性--这是现有方法通常缺乏的一种细致入微的方法。我们在真实世界肺腺癌 NGS 数据集上的验证结果表明,该系统不仅提高了识别基因靶点的效率,还具有简化临床工作流程的潜力,从而推动了精准肿瘤学的发展。未来的改进计划包括扩大集成数据类型的范围和开发用户友好型界面,旨在方便数据访问,促进癌症治疗的定制化合作。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Prioritizing Clinically Significant Lung Cancer Somatic Mutations for Targeted Therapy Through Efficient NGS Data Filtering System.

In the realm of lung cancer treatment, where genetic heterogeneity presents formidable challenges, precision oncology demands an exacting approach to identify and hierarchically sort clinically significant somatic mutations. Current Next-Generation Sequencing (NGS) data filtering pipelines, while utilizing various external databases for mutation screening, often fall short in comprehensive integration and flexibility needed to keep pace with the evolving landscape of clinical data. Our study introduces a sophisticated NGS data filtering system, which not only aggregates but effectively synergizes diverse data sources, encompassing genetic variants, gene functions, clinical evidence, and an extensive body of literature. This system is distinguished by a unique algorithm that facilitates a rigorous, multi-tiered filtration process. This allows for the efficient prioritization of 420 genes and 1,193 variants from large datasets, with a particular focus on 80 variants demonstrating high clinical actionability. These variants have been aligned with FDA approvals, NCCN guidelines, and thoroughly reviewed literature, thereby equipping oncologists with a refined arsenal for targeted therapy decisions. The innovation of our system lies in its dynamic integration framework and its algorithm, tailored to emphasize clinical utility and actionability-a nuanced approach often lacking in existing methodologies. Our validation on real-world lung adenocarcinoma NGS datasets has shown not only an enhanced efficiency in identifying genetic targets but also the potential to streamline clinical workflows, thus propelling the advancement of precision oncology. Planned future enhancements include expanding the range of integrated data types and developing a user-friendly interface, aiming to facilitate easier access to data and promote collaborative efforts in tailoring cancer treatments.

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