MSIseq: Software for Assessing Microsatellite Instability from Catalogs of Somatic Mutations.

Published online

Journal Article

Microsatellite instability (MSI) is a form of hypermutation that occurs in some tumors due to defects in cellular DNA mismatch repair. MSI is characterized by frequent somatic mutations (i.e., cancer-specific mutations) that change the length of simple repeats (e.g., AAAAA…., GATAGATAGATA...). Clinical MSI tests evaluate the lengths of a handful of simple repeat sites, while next-generation sequencing can assay many more sites and offers a much more complete view of their somatic mutation frequencies. Using somatic mutation data from the exomes of a 361-tumor training set, we developed classifiers to determine MSI status based on four machine-learning frameworks. All frameworks had high accuracy, and after choosing one we determined that it had >98% concordance with clinical tests in a separate 163-tumor test set. Furthermore, this classifier retained high concordance even when classifying tumors based on subsets of whole-exome data. We have released a CRAN R package, MSIseq, based on this classifier. MSIseq is faster and simpler to use than software that requires large files of aligned sequenced reads. MSIseq will be useful for genomic studies in which clinical MSI test results are unavailable and for detecting possible misclassifications by clinical tests.

Full Text

Duke Authors

Cited Authors

  • Huang, MN; McPherson, JR; Cutcutache, I; Teh, BT; Tan, P; Rozen, SG

Published Date

  • August 26, 2015

Published In

Volume / Issue

  • 5 /

Start / End Page

  • 13321 -

PubMed ID

  • 26306458

Pubmed Central ID

  • 26306458

Electronic International Standard Serial Number (EISSN)

  • 2045-2322

Digital Object Identifier (DOI)

  • 10.1038/srep13321

Language

  • eng

Conference Location

  • England