MSIsensor-ct：使用 cfDNA 测序数据检测微卫星不稳定性。

MSIsensor-ct: microsatellite instability detection using cfDNA sequencing data.

机构信息

Computer Network Information Center, Chinese Academy of Sciences, Beijing 100190, China.

University of the Chinese Academy of Sciences, Beijing 100190, China.

出版信息

Brief Bioinform. 2021 Sep 2;22(5). doi: 10.1093/bib/bbaa402.

DOI:10.1093/bib/bbaa402

PMID:33461213

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8424396/

Abstract

MOTIVATION

Microsatellite instability (MSI) is a promising biomarker for cancer prognosis and chemosensitivity. Techniques are rapidly evolving for the detection of MSI from tumor-normal paired or tumor-only sequencing data. However, tumor tissues are often insufficient, unavailable, or otherwise difficult to procure. Increasing clinical evidence indicates the enormous potential of plasma circulating cell-free DNA (cfNDA) technology as a noninvasive MSI detection approach.

RESULTS

We developed MSIsensor-ct, a bioinformatics tool based on a machine learning protocol, dedicated to detecting MSI status using cfDNA sequencing data with a potential stable MSIscore threshold of 20%. Evaluation of MSIsensor-ct on independent testing datasets with various levels of circulating tumor DNA (ctDNA) and sequencing depth showed 100% accuracy within the limit of detection (LOD) of 0.05% ctDNA content. MSIsensor-ct requires only BAM files as input, rendering it user-friendly and readily integrated into next generation sequencing (NGS) analysis pipelines.

AVAILABILITY

MSIsensor-ct is freely available at https://github.com/niu-lab/MSIsensor-ct.

SUPPLEMENTARY INFORMATION

Supplementary data are available at Briefings in Bioinformatics online.

摘要

动机

微卫星不稳定性 (MSI) 是一种有前途的癌症预后和化疗敏感性生物标志物。从肿瘤-正常配对或仅肿瘤测序数据中检测 MSI 的技术正在迅速发展。然而，肿瘤组织通常不足、无法获得或难以获取。越来越多的临床证据表明，血浆循环无细胞 DNA (cfNDA) 技术作为一种非侵入性 MSI 检测方法具有巨大的潜力。

结果

我们开发了 MSIsensor-ct，这是一种基于机器学习协议的生物信息学工具，专门用于使用 cfDNA 测序数据检测 MSI 状态，潜在的稳定 MSIscore 阈值为 20%。在具有不同循环肿瘤 DNA (ctDNA) 和测序深度的独立测试数据集上评估 MSIsensor-ct 表明，在检测限 (LOD) 为 0.05% ctDNA 含量的范围内，准确率为 100%。MSIsensor-ct 仅需要 BAM 文件作为输入，使其易于使用，并可轻松集成到下一代测序 (NGS) 分析管道中。