MSIsensor-pro: Fast, Accurate, and Matched-normal-sample-free Detection of Microsatellite Instability
MSIsensor-pro: Fast, Accurate, and Matched-normal-sample-free Detection of Microsatellite Instability
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MSIsensor-pro：快速、准确、无匹配正态样本的微卫星不稳定性检测
DOI：
10.1016/j.gpb.2020.02.001
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发表时间：
2020-02-01
影响因子：
9.5
通讯作者：
Ye, Kai
中科院分区：
文献类型：
--
作者：
Jia, Peng;Yang, Xiaofei;Ye, Kai
微卫星不稳定性（MSI）是癌症治疗和预后的关键生物标志物。反式实验测定是费力且耗时的，并且由于需要匹配的正常样品，下一代基于测序的计算方法对白血病样品、石蜡包埋的样品或患者来源的异种移植物/类器官不起作用。在此，我们开发了MSISensor-pro，这是一种用于研究和临床应用的开源单样本MSI评分方法。MSISensor-pro引入了一个多项分布模型来量化每个肿瘤样本的聚合酶滑动，并引入了一种判别性位点选择方法来实现MSI检测，而无需匹配的正常样本。我们证明了MSISensor-pro是一种超快，准确和强大的MSI调用方法。使用具有不同测序深度和肿瘤纯度的样本，MSISensor-pro在准确性和计算成本方面均显著优于当前领先的方法。MSISensor-pro可在https://github.com/xjtu-omics/msisensor-pro上获得，可免费用于非商业用途，但可根据要求提供商业许可证。
Microsatellite instability (MSI) is a key biomarker for cancer therapy and prognosis. Tra-ditional experimental assays are laborious and time-consuming, and next-generation sequencing -based computational methods do not work on leukemia samples, paraffin-embedded samples, or patient-derived xenografts/organoids, due to the requirement of matched normal samples. Herein, we developed MSIsensor-pro, an open-source single sample MSI scoring method for research and clinical applications. MSIsensor-pro introduces a multinomial distribution model to quantify poly-merase slippages for each tumor sample and a discriminative site selection method to enable MSI detection without matched normal samples. We demonstrate that MSIsensor-pro is an ultrafast, accurate, and robust MSI calling method. Using samples with various sequencing depths and tumor purities, MSIsensor-pro significantly outperformed the current leading methods in both accuracy and computational cost. MSIsensor-pro is available at https://github.com/xjtu-omics/msisensor-pro and free for non-commercial use, while a commercial license is provided upon request.