MSIsensor-Pro: Fast, Accurate, and Matched-Normal-Sample-Free Detection of Microsatellite Instability

Genomics Proteomics & Bioinformatics, vol. 18, pp. 65–71

Abstract

Microsatellite instability (MSI) is a key biomarker for cancer therapy and prognosis. Traditional 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 polymerase 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.

Authors 8

1. Peng Jia

   Xi'an Jiaotong University

   Affiliation as printed

   MOE Key Laboratory for Intelligent Networks & Networks Security, Faculty of Electronic and Information Engineering, Xi’an Jiaotong University , Xi’an 710049 , China

   School of Automation Science and Engineering, Faculty of Electronic and Information Engineering, Xi’an Jiaotong University , Xi’an 710049 , China

2. Xiaofei Yang

   Xi'an Jiaotong University

   Affiliation as printed

   MOE Key Laboratory for Intelligent Networks & Networks Security, Faculty of Electronic and Information Engineering, Xi’an Jiaotong University , Xi’an 710049 , China

   School of Computer Science and Technology, Faculty of Electronic and Information Engineering, Xi’an Jiaotong University , Xi’an 710049 , China

3. Li Guo

   Xi'an Jiaotong University

   Affiliation as printed

   MOE Key Laboratory for Intelligent Networks & Networks Security, Faculty of Electronic and Information Engineering, Xi’an Jiaotong University , Xi’an 710049 , China

   School of Automation Science and Engineering, Faculty of Electronic and Information Engineering, Xi’an Jiaotong University , Xi’an 710049 , China

   School of Life Science and Technology, Xi’an Jiaotong University , Xi’an 710049 , China

4. Bowen Liu

   Xi'an Jiaotong University

   Affiliation as printed

   MOE Key Laboratory for Intelligent Networks & Networks Security, Faculty of Electronic and Information Engineering, Xi’an Jiaotong University , Xi’an 710049 , China

   School of Automation Science and Engineering, Faculty of Electronic and Information Engineering, Xi’an Jiaotong University , Xi’an 710049 , China

5. Jiadong Lin Aachen Leiden Institute of Advanced Computer Science

   Leiden University · Xi'an Jiaotong University

   Affiliation as printed

   Leiden Institute of Advanced Computer Science, Leiden University , Leiden 2311 ZE , Netherlands

   MOE Key Laboratory for Intelligent Networks & Networks Security, Faculty of Electronic and Information Engineering, Xi’an Jiaotong University , Xi’an 710049 , China

   School of Automation Science and Engineering, Faculty of Electronic and Information Engineering, Xi’an Jiaotong University , Xi’an 710049 , China

6. Jianyong Sun

   Xi'an Jiaotong University

   Affiliation as printed

   School of Mathematics and Statistics, Xi’an Jiaotong University , Xi’an 710049 , China

7. Chengsheng Zhang

   First Affiliated Hospital of Xi'an Jiaotong University · The Jackson Laboratory for Genomic Medicine

   Affiliation as printed

   Jackson Laboratory for Genomic Medicine, Farmington , CT 06032 , USA

   Precision Medicine Center, the First Affiliated Hospital of Xi’an Jiaotong University , Xi’an 710061 , China

8. Kai Ye corresponding

   First Affiliated Hospital of Xi'an Jiaotong University · Xi'an Jiaotong University

   Affiliation as printed

   Genome Institute, the First Affiliated Hospital of Xi’an Jiaotong University , Xi’an 710061 , China

   MOE Key Laboratory for Intelligent Networks & Networks Security, Faculty of Electronic and Information Engineering, Xi’an Jiaotong University , Xi’an 710049 , China

   School of Automation Science and Engineering, Faculty of Electronic and Information Engineering, Xi’an Jiaotong University , Xi’an 710049 , China

   School of Life Science and Technology, Xi’an Jiaotong University , Xi’an 710049 , China