title: Mitochondrial Disease Sequence Data Resource (MSeqDR): a global grass-roots consortium to facilitate deposition, curation, annotation, and integrated analysis of genomic data for the mitochondrial disease clinical and research communities.
abstract: Success rates for genomic analyses of highly heterogeneous disorders can be greatly improved if a large cohort of patient data is assembled to enhance collective capabilities for accurate sequence variant annotation, analysis, and interpretation. Indeed, molecular diagnostics requires the establishment of robust data resources to enable data sharing that informs accurate understanding of genes, variants, and phenotypes. The "Mitochondrial Disease Sequence Data Resource (MSeqDR) Consortium" is a grass-roots effort facilitated by the United Mitochondrial Disease Foundation to identify and prioritize specific genomic data analysis needs of the global mitochondrial disease clinical and research community. A central Web portal (https://mseqdr.org) facilitates the coherent compilation, organization, annotation, and analysis of sequence data from both nuclear and mitochondrial genomes of individuals and families with suspected mitochondrial disease. This Web portal provides users with a flexible and expandable suite of resources to enable variant-, gene-, and exome-level sequence analysis in a secure, Web-based, and user-friendly fashion. Users can also elect to share data with other MSeqDR Consortium members, or even the general public, either by custom annotation tracks or through the use of a convenient distributed annotation system (DAS) mechanism. A range of data visualization and analysis tools are provided to facilitate user interrogation and understanding of genomic, and ultimately phenotypic, data of relevance to mitochondrial biology and disease. Currently available tools for nuclear and mitochondrial gene analyses include an MSeqDR GBrowse instance that hosts optimized mitochondrial disease and mitochondrial DNA (mtDNA) specific annotation tracks, as well as an MSeqDR locus-specific database (LSDB) that curates variant data on more than 1300 genes that have been implicated in mitochondrial disease and/or encode mitochondria-localized proteins. MSeqDR is integrated with a diverse array of mtDNA data analysis tools that are both freestanding and incorporated into an online exome-level dataset curation and analysis resource (GEM.app) that is being optimized to support needs of the MSeqDR community. In addition, MSeqDR supports mitochondrial disease phenotyping and ontology tools, and provides variant pathogenicity assessment features that enable community review, feedback, and integration with the public ClinVar variant annotation resource. A centralized Web-based informed consent process is being developed, with implementation of a Global Unique Identifier (GUID) system to integrate data deposited on a given individual from different sources. Community-based data deposition into MSeqDR has already begun. Future efforts will enhance capabilities to incorporate phenotypic data that enhance genomic data analyses. MSeqDR will fill the existing void in bioinformatics tools and centralized knowledge that are necessary to enable efficient nuclear and mtDNA genomic data interpretation by a range of shareholders across both clinical diagnostic and research settings. Ultimately, MSeqDR is focused on empowering the global mitochondrial disease community to better define and explore mitochondrial diseases.
authors.affiliation: Division of Human Genetics, Department of Pediatrics, The Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, USA. Electronic address: falkm@email.chop.edu.
authors.forename: Marni J
authors.initials: MJ
authors.lastname: Falk
authors.affiliation: Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA.
authors.forename: Lishuang
authors.initials: L
authors.lastname: Shen
authors.affiliation: Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, FL, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Gonzalez
authors.affiliation: Center for Biomedical Informatics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Leipzig
authors.affiliation: Center for Mitochondrial and Epigenomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Marie T
authors.initials: MT
authors.lastname: Lott
authors.affiliation: Department of Clinical Genetics, Maastricht University Medical Centre, The Netherlands.
authors.forename: Alphons P M
authors.initials: AP
authors.lastname: Stassen
authors.affiliation: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy.
authors.forename: Maria Angela
authors.initials: MA
authors.lastname: Diroma
authors.affiliation: Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Navarro-Gomez
authors.affiliation: United Mitochondrial Disease Foundation, Pittsburgh, PA, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Yeske
authors.affiliation: GeneDx Inc., Gaithersburg, MD, USA.
authors.forename: Renkui
authors.initials: R
authors.lastname: Bai
authors.affiliation: Courtagen Life Sciences, Woburn, MA, USA.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Boles
authors.affiliation: Research Programs Unit, Molecular Neurology, Biomedicum Helsinki, University of Helsinki, Finland.
authors.forename: Virginia
authors.initials: V
authors.lastname: Brilhante
authors.affiliation: Transgenomic, Inc., New Haven, CT, USA.
authors.forename: David
authors.initials: D
authors.lastname: Ralph
authors.affiliation: Transgenomic, Inc., New Haven, CT, USA.
authors.forename: Jeana T
authors.initials: JT
authors.lastname: DaRe
authors.affiliation: Private Access, CA, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Shelton
authors.affiliation: Genetic Alliance, Bethesda, MD, USA.
authors.forename: Sharon F
authors.initials: SF
authors.lastname: Terry
authors.affiliation: Center for Biomedical Informatics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Copeland
authors.affiliation: Department of Forensic Molecular Biology, Erasmus MC - University Medical Center Rotterdam, The Netherlands.
authors.forename: Mannis
authors.initials: M
authors.lastname: van Oven
authors.affiliation: Institute of Human Genetics, Technical University Munich and Helmholtz Zentrum Munich, Munich, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Prokisch
authors.affiliation: Center for Mitochondrial and Epigenomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pathology, The Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Wallace
authors.affiliation: Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Attimonelli
authors.affiliation: National Institute of Child Health and Development, The National Institutes of Health, Bethesda, MD, USA.
authors.forename: Danuta
authors.initials: D
authors.lastname: Krotoski
authors.affiliation: Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, FL, USA.
authors.forename: Stephan
authors.initials: S
authors.lastname: Zuchner
authors.affiliation: Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA. Electronic address: Xiaowu_Gai@meei.harvard.edu.
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Gai
mesh_terms: D019295:Computational Biology; D030541:Databases, Genetic; D059472:Exome; D005260:Female; D054629:Genome, Mitochondrial; D023281:Genomics; D006801:Humans; D033181:Information Dissemination; D020407:Internet; D008297:Male; D028361:Mitochondrial Diseases / Q000235:genetics; D010641:Phenotype; D012984:Software; D014584:User-Computer Interface
keywords: Data sharing; Exome; Genomics; Mitochondrial disease