Common mitochondrial deletions in RNA-Seq: evaluation of bulk, single-cell, and spatial transcriptomic datasets

Audrey A. Omidsalar, Carmel G. McCullough, Lili Xu, Stanley Boedijono, Daniel Gerke, Michelle G. Webb, Zarko Manojlovic, Adolfo Sequeira, Mark F. Lew, Marco Santorelli, Geidy E. Serrano, Thomas G. Beach, Agenor Limon, Marquis P. Vawter, Brooke E. Hjelm

Research output: Contribution to journalArticlepeer-review


Common mitochondrial DNA (mtDNA) deletions are large structural variants in the mitochondrial genome that accumulate in metabolically active tissues with age and have been investigated in various diseases. We applied the Splice-Break2 pipeline (designed for high-throughput quantification of mtDNA deletions) to human RNA-Seq datasets and describe the methodological considerations for evaluating common deletions in bulk, single-cell, and spatial transcriptomics datasets. A robust evaluation of 1570 samples from 14 RNA-Seq studies showed: (i) the abundance of some common deletions detected in PCR-amplified mtDNA correlates with levels observed in RNA-Seq data; (ii) RNA-Seq library preparation method has a strong effect on deletion detection; (iii) deletions had a significant, positive correlation with age in brain and muscle; (iv) deletions were enriched in cortical grey matter, specifically in layers 3 and 5; and (v) brain regions with dopaminergic neurons (i.e., substantia nigra, ventral tegmental area, and caudate nucleus) had remarkable enrichment of common mtDNA deletions.

Original languageEnglish (US)
Article number200
JournalCommunications Biology
Issue number1
StatePublished - Dec 2024
Externally publishedYes

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • General Biochemistry, Genetics and Molecular Biology
  • General Agricultural and Biological Sciences


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