mtDNA-Server: next-generation sequencing data analysis of human mitochondrial DNA in the cloud
Open accessAbstract
Next generation sequencing (NGS) allows investigating mitochondrial DNA (mtDNA) characteristics such as heteroplasmy (i.e. intra-individual sequence variation) to a higher level of detail. While several pipelines for analyzing heteroplasmies exist, issues in usability, accuracy of results and interpreting final data limit their usage. Here we present mtDNA-Server, a scalable web server for the analysis of mtDNA studies of any size with a special focus on usability as well as reliable identification and quantification of heteroplasmic variants. The mtDNA-Server workflow includes parallel read alignment, heteroplasmy detection, artefact or contamination identification, variant annotation as well as several quality control metrics, often neglected in current mtDNA NGS studies. All computational steps are parallelized with Hadoop MapReduce and executed graphically with Cloudgene. We validated the underlying heteroplasmy and contamination detection model by generating four artificial sample mix-ups on two different NGS devices. Our evaluation data shows that mtDNA-Server detects heteroplasmies and artificial recombinations down to the 1% level with perfect specificity and outperforms existing approaches regarding sensitivity. mtDNA-Server is currently able to analyze the 1000G Phase 3 data (n = 2,504) in less than 5 h and is freely accessible at https://mtdna-server.uibk.ac.at.
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All five Sidon_BA individuals had different mitochondrial DNA haplotypes, belonging to paragroups common in present-day Lebanon and nearby regions but with additional derived variants not observed in the present-day Lebanese dataset.
“All five Sidon_BA individuals had different mitochondrial DNA haplotypes49 (Table 1), belonging to paragroups common in present-day Lebanon and nearby regions (Table S5) but with additional derived variants not observed in our present-day Lebanese dataset.”
From Continuity and Admixture in the Last Five Millennia of Levantine History from Ancient Canaanite and Present-Day Lebanese Genome Sequences (2017) · cites this paper as [49]
The Materials and Methods section describes mtDNA-Server’s variant detection, and the Results (Data output) section describes its haplogroup reports. Neither reports findings for Sidon_BA individuals or compares their haplotypes with a present-day Lebanese dataset. Searches for Sidon_BA and for Lebanese paragroups and derived variants found no passage addressing the claim. (LLM, conf=0.77)
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- Authors
- Weissensteiner, H., Forer, L., Fuchsberger, C., Schöpf, B., Kloss-Brandstätter, A., Specht, G., Kronenberg, F., & Schönherr, S.
- Affiliations
- Innsbruck Medical University (AT)
- Universität Innsbruck (AT)
- Corresponding author
- Weissensteiner, Hansi
- Forer, Lukas
- Schönherr, Sebastian
- ORCID
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-04-15
- Volume
- 44
- Issue
- W1
- Pages
- W64-W69
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC4987870
- OpenAlex
- W2339839936
- Cited by
- 188
- References
- 32
- Citations by year
- 2026: 11 · 2025: 12 · 2024: 36 · 2023: 21 · 2022: 19 · 2021: 24 · 2020: 21 · 2019: 20 · 2018: 12 · 2017: 10 · 2016: 2
- FWCI
- 7.63
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleic Acids Research (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Forensic and Genetic Research
- Keywords
- mitochondrial DNA, heteroplasmy, web server, cloud computing, Hadoop MapReduce, contamination detection, artifact detection, variant annotation, quality control metrics, 1000 Genomes Project
- MeSH terms
- Computer Graphics, DNA, Mitochondrial, Humans, Mitochondria, Sensitivity and Specificity, User-Computer Interface, Genetic Variation, Sequence Alignment, Sequence Analysis, DNA, Internet, Molecular Sequence Annotation, High-Throughput Nucleotide Sequencing
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