William L. Macken, Micol Falabella, Chiara Pizzamiglio, Cathy E. Woodward, Elizabeth Scotchman, Lyn S. Chitty, James M. Polke, Enrico Bugiardini, Michael G. Hanna, Jana Vandrovcova, Natalie Chandler, Robyn Labrum, Robert D.S. Pitceathly
Abstract
Primary mitochondrial diseases (PMDs) comprise a large and heterogeneous group of genetic diseases that result from pathogenic variants in either nuclear DNA (nDNA) or mitochondrial DNA (mtDNA). Widespread adoption of next-generation sequencing (NGS) has improved the efficiency and accuracy of mtDNA diagnoses; however, several challenges remain.
In this review, we briefly summarize the current state of the art in molecular diagnostics for mtDNA and consider the implications of improved whole genome sequencing (WGS), bioinformatic techniques, and the adoption of long-read sequencing, for PMD diagnostics.
We anticipate that the application of PCR-free WGS from blood DNA will increase in diagnostic laboratories, while for adults with myopathic presentations, WGS from muscle DNA may become more widespread. Improved bioinformatic strategies will enhance WGS data interrogation, with more accurate delineation of mtDNA and NUMTs (nuclear mitochondrial DNA segments) in WGS data, superior coverage uniformity, indirect measurement of mtDNA copy number, and more accurate interpretation of heteroplasmic large-scale rearrangements (LSRs). Separately, the adoption of diagnostic long-read sequencing could offer greater resolution of complex LSRs and the opportunity to phase heteroplasmic variants.
This research output has an Altmetric Attention Score of 18. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 18 June 2024.
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#2,143,917
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#33
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#37,125
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Outputs of similar age from Expert Review of Molecular Diagnostics
#3
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Altmetric has tracked 26,233,985 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 91st percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,056 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.2. This one has done particularly well, scoring higher than 96% of its peers.
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We're also able to compare this research output to 13 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 76% of its contemporaries.
