Noninvasive prenatal testing (NIPT) consists of determining fetal aneuploidies by quantifying copy number alteration from the sequencing of cell-free DNA (cfDNA) from maternal blood. Due to the presence of cfDNA of fetal origin in maternal blood, in silico approaches have been developed to accurately predict fetal aneuploidies. Although NIPT is becoming a new standard in prenatal screening of chromosomal abnormalities, there are no integrated pipelines available to allow rapid, accurate and standardized data analysis in any clinical setting. Several tools have been developed, however often optimized only for research purposes or requiring enormous amount of retrospective data, making hard their implementation in a clinical context. Furthermore, no guidelines have been provided on how to accomplish each step of the data analysis to achieve reliable results. Finally, there is no integrated pipeline to perform all steps of NIPT analysis. To address these needs, we tested several tools for performing NIPT data analysis. We provide extensive benchmark of tools performances but also guidelines for running them. We selected the best performing tools that we benchmarked and gathered them in a computational pipeline. NiPTUNE is an open source python package that includes methods for fetal fraction estimation, a novel method for accurate gender prediction, a principal component analysis based strategy for quality control and fetal aneuploidies prediction. NiPTUNE is constituted by seven modules allowing the user to run the entire pipeline or each module independently. Using two cohorts composed by 1439 samples with 31 confirmed aneuploidies, we demonstrated that NiPTUNE is a valuable resource for NIPT analysis.

中文翻译：

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NiPTUNE：在准确、综合和灵活的框架中进行无创产前检测的自动化管道

无创产前检测 (NIPT) 包括通过量化来自母体血液的无细胞 DNA (cfDNA) 测序的拷贝数变化来确定胎儿非整倍体。由于母体血液中存在胎儿来源的 cfDNA，因此已开发出计算机方法来准确预测胎儿非整倍体。尽管 NIPT 正在成为染色体异常产前筛查的新标准，但没有可用于在任何临床环境中进行快速、准确和标准化数据分析的集成管道。已经开发了几种工具，但通常仅出于研究目的或需要大量回顾性数据进行优化，这使得它们难以在临床环境中实施。此外，没有提供关于如何完成数据分析的每个步骤以获得可靠结果的指南。最后，没有集成的管道来执行 NIPT 分析的所有步骤。为了满足这些需求，我们测试了几种用于执行 NIPT 数据分析的工具。我们提供广泛的工具性能基准测试以及运行它们的指南。我们选择了我们进行基准测试的性能最佳的工具，并将它们收集在一个计算管道中。NiPTUNE 是一个开源 python 包，包括胎儿分数估计方法、准确性别预测的新方法、基于主成分分析的质量控制策略和胎儿非整倍体预测。NiPTUNE 由七个模块组成，允许用户独立运行整个管道或每个模块。