Bioinformatics Tools and Databases to Assess the Pathogenicity of Mitochondrial DNA Variants in the Field of Next Generation Sequencing

@article{Bris2018BioinformaticsTA,
  title={Bioinformatics Tools and Databases to Assess the Pathogenicity of Mitochondrial DNA Variants in the Field of Next Generation Sequencing},
  author={C{\'e}line Bris and David Gouden{\`e}ge and V Desquiret-Dumas and Majida Charif and Estelle Colin and Dominique Bonneau and Patrizia Amati‐Bonneau and Guy Lenaers and Pascal Reynier and Vincent Procaccio},
  journal={Frontiers in Genetics},
  year={2018},
  volume={9}
}
The development of next generation sequencing (NGS) has greatly enhanced the diagnosis of mitochondrial disorders, with a systematic analysis of the whole mitochondrial DNA (mtDNA) sequence and better detection sensitivity. However, the exponential growth of sequencing data renders complex the interpretation of the identified variants, thereby posing new challenges for the molecular diagnosis of mitochondrial diseases. Indeed, mtDNA sequencing by NGS requires specific bioinformatics tools and… 

Figures and Tables from this paper

Benchmarking the Effectiveness and Accuracy of Multiple Mitochondrial DNA Variant Callers: Practical Implications for Clinical Application

It is found that resources like population frequency databases and pathogenicity predictors are now available for variant annotation but still need refinement and improvement, and Mutserve showed the best performance using the synthetic benchmark dataset.

MitoMut: An Efficient Approach to Detecting Mitochondrial DNA Deletions from Paired-end Next-generation Sequencing Data

MitoMut is presented, a tool capable of efficiently and effectively analyzing mitochondrial deletions while maintaining user freedom and consistently outperforms alternate approaches in both time and space efficiency, as well as overall sensitivity.

Genetic basis of mitochondrial diseases

The current status of the genetic basis of mitochondrial diseases is covered, current challenges and perspectives are discussed, and the contribution of factors beyond the protein‐coding regions and monogenic inheritance in the expansion of the Genetic spectrum of disease is explored.

Specifications of the ACMG/AMP standards and guidelines for mitochondrial DNA variant interpretation

This group reviewed the 2015 American College of Medical Genetics and Association of Molecular Pathology standards and guidelines that are widely used for clinical interpretation of DNA sequence variants and provided further specifications for additional and specific guidance related to mtDNA variant classification.

Multi-Omics Approaches to Improve Mitochondrial Disease Diagnosis: Challenges, Advances, and Perspectives

A novel data-driven classification of mitochondrial diseases is proposed and how multi-omics will change and improve the diagnosis of MD is discussed, foreseeing that this work will contribute to set up good practices to performMulti-omics data integration to improve the prediction of phenotypic outcomes and the diagnostic power of MD.

From Forensics to Clinical Research: Expanding the Variant Calling Pipeline for the Precision ID mtDNA Whole Genome Panel

The PrecisionCallerPipeline (PCP) is presented, for processing samples with the correct rCRS output after Ion Torrent sequencing with the Precision ID library kit, and achieved overall improved performance metrics in comparison with the proprietary TSS.

Mitochondrial DNA Changes in Genes of Respiratory Complexes III, IV and V Could Be Related to Brain Tumours in Humans

The study investigated the effects of missense mutations on the biochemical properties, structure and functioning of the encoded protein, as well as their potential harmfulness, and assessed the G8959A (E145K) ATP6 missense mutation as harmful alterations that could be involved in oncogenesis.

A Novel Approach for the Identification of Pharmacogenetic Variants in MT-RNR1 through Next-Generation Sequencing Off-Target Data

This study shows that obtaining MT-RNR1 genotypes through off-target reads is an efficient strategy that can impulse preemptive pharmacogenetic screening of this mitochondrial gene.

References

SHOWING 1-10 OF 127 REFERENCES

Comprehensive one-step molecular analyses of mitochondrial genome by massively parallel sequencing.

This "deep" sequencing approach provides a 1-step comprehensive molecular analysis of the whole mitochondrial genome for patients in whom a mitochondrial disease is suspected.

Transition to Next Generation Analysis of the Whole Mitochondrial Genome: A Summary of Molecular Defects

A new era of more efficient molecular diagnosis of mtDNA mutations has arrived as the recently developed “Next‐Generation Sequencing” (NGS) technology offers a robust high‐throughput platform for comprehensive mtDNA analysis.

Mitochondrial DNA Variant Discovery and Evaluation in Human Cardiomyopathies through Next-Generation Sequencing

A potential role of next-generation sequencing in the discovery of novel mtDNA variants with heteroplasmy below the level reliably detected with Sanger sequencing is supported.

Mitochondrial genome variation and the origin of modern humans

The global mtDNA diversity in humans is described based on analyses of the complete mtDNA sequence of 53 humans of diverse origins, providing a concurrent view on human evolution with respect to the age of modern humans.

Analysis of the whole mitochondrial genome: translation of the Ion Torrent Personal Genome Machine system to the diagnostic bench?

The majority of all nucleotide alterations were identified, but three false-negative results were also encountered in the data set, and the poor performance of the PGM instrument in regions associated with homopolymeric stretches generated many false-positive miscalls demanding additional manual curation of the data.

Surveyor™ Nuclease: A new strategy for a rapid identification of heteroplasmic mitochondrial DNA mutations in patients with respiratory chain defects

This method can be effectively used to rapidly and completely screen the entire human mitochondrial genome for heteroplasmic mutations and in this context represents an important advance for the diagnosis of mitochondrial diseases.

mtDNA-Server: next-generation sequencing data analysis of human mitochondrial DNA in the cloud

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

Accurate mitochondrial DNA sequencing using off-target reads provides a single test to identify pathogenic point mutations

This work compared the mitochondrial DNA sequence derived from off-target exome reads with conventional mitochondrial DNA Sanger sequencing in 46 subjects to offer the prospect of using whole-exome sequence in a diagnostic setting to screen not only all protein coding nuclear genes but also all mitochondrial DNA genes for pathogenic mutations.

mit‐o‐matic: A Comprehensive Computational Pipeline for Clinical Evaluation of Mitochondrial Variations from Next‐Generation Sequencing Datasets

A computational and experimental pipeline to decipher the human mitochondrial DNA variations and examine them for their clinical correlation is reported and made available as a user‐friendly online tool to annotate variants and find haplogroup, disease association, and heteroplasmic sites.
...