MSIsensor-ct: microsatellite instability detection using cfDNA sequencing data

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

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.

Keywords: MSI; cfDNA; ctDNA; machine learning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Circulating Tumor DNA / blood
  • Circulating Tumor DNA / genetics*
  • Computational Biology / methods
  • High-Throughput Nucleotide Sequencing / statistics & numerical data
  • Humans
  • Limit of Detection
  • Machine Learning*
  • Microsatellite Instability*
  • Microsatellite Repeats
  • Neoplasms / blood
  • Neoplasms / diagnosis
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Sequence Analysis, DNA
  • Software*

Substances

  • Circulating Tumor DNA