"NanoDel": identification of large-scale mitochondrial DNA deletions using long-read sequencing.

Long-read, splice-aware alignment pipeline to identify and quantify breakpoints of mitochondrial DNA deletions without a priori information.

NanoDel is a long-read pipeline combining a splice-aware alignment tool with Oxford Nanopore sequencing to detect large-scale mitochondrial DNA deletions (LSMDs) without a priori information. On artificial datasets, it was more sensitive and accurate than the other pipelines compared. In samples from patients with mitochondrial disease, it identified both known and previously uncharacterised LSMDs, including mixtures. Analysis of selected deletions points to a vulnerability of mtDNA shaped by sequence motifs (repeats, putative G-quadruplex motifs) and the contact zone. The pipeline is open source (GitHub, archived on Zenodo) and paired with a one-amplicon LR-PCR.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

A useful tool for mitochondrial diagnostics, since it removes the need for a priori information and handles mixtures of deletions. The authors themselves describe the study as a proof of concept: superiority over other pipelines is shown on artificial data, and validation in larger cohorts is still needed. The open-source code allows independent evaluation.

Analysis by Dr Thibaut Benquey