eKLIPse: a sensitive tool for the detection and quantification of mitochondrial DNA deletions from next-generation sequencing data

Genet Med. 2019 Jun;21(6):1407-1416. doi: 10.1038/s41436-018-0350-8. Epub 2018 Nov 5.


Purpose: Accurate detection of mitochondrial DNA (mtDNA) alterations is essential for the diagnosis of mitochondrial diseases. The development of high-throughput sequencing technologies has enhanced the detection sensitivity of mtDNA pathogenic variants, but the detection of mtDNA rearrangements, especially multiple deletions, is still poorly processed. Here, we present eKLIPse, a sensitive and specific tool allowing the detection and quantification of large mtDNA rearrangements from single and paired-end sequencing data.

Methods: The methodology was first validated using a set of simulated data to assess the detection sensitivity and specificity, and second with a series of sequencing data from mitochondrial disease patients carrying either single or multiple deletions, related to pathogenic variants in nuclear genes involved in mtDNA maintenance.

Results: eKLIPse provides the precise breakpoint positions and the cumulated percentage of mtDNA rearrangements at a given gene location with a detection sensitivity lower than 0.5% mutant. eKLIPse software is available either as a script to be integrated in a bioinformatics pipeline, or as user-friendly graphical interface to visualize the results through a Circos representation ( https://github.com/dooguypapua/eKLIPse ).

Conclusion: Thus, eKLIPse represents a useful resource to study the causes and consequences of mtDNA rearrangements, for further genotype/phenotype correlations in mitochondrial disorders.

Keywords: mitochondrial diseases; mitochondrial genome; mtDNA deletions; next-generation sequencing; soft clipping.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence / genetics
  • DNA, Mitochondrial / genetics*
  • Genetic Association Studies
  • High-Throughput Nucleotide Sequencing / methods
  • Humans
  • Mitochondria / genetics
  • Mitochondrial Diseases / diagnosis
  • Sequence Analysis, DNA / methods*
  • Sequence Deletion / genetics*
  • Software


  • DNA, Mitochondrial