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.
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.
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DOI：
10.1016/j.ymgme.2014.11.016
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发表时间：
2015-03
影响因子：
3.8
通讯作者：
Claire Sheldon, Eric A. Shoubridge, Domenico Simone, Bert Smeets, Jan A. Smeitink, Christine Stanley, Anu Suomalainen, Mark Tarnopolsky, Isabelle Thiffault, David R. Thorburn, Johan Van Hove, Lynne Wolfe, and Lee-Jun Wong
中科院分区：
文献类型：
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作者：
Falk MJ;Shen L;Gonzalez M;Leipzig J;Lott MT;Stassen AP;Diroma MA;Navarro-Gomez D;Yeske P;Bai R;Boles RG;Brilhante V;Ralph D;DaRe JT;Shelton R;Terry SF;Zhang Z;Copeland WC;van Oven M;Prokisch H;Wallace DC;Attimonelli M;Krotoski D;Zuchner S;Gai X;MSeqDR Consortium Participants;MSeqDR Consortium participants: Sherri Bale, Jirair Bedoyan, Doron Behar, Penelope Bonnen, Lisa Brooks, Claudia Calabrese, Sarah Calvo, Patrick Chinnery, John Christodoulou, Deanna Church,;Rosanna Clima, Bruce H. Cohen, Richard G. Cotton, IFM de Coo, Olga Derbenevoa, Johan T. den Dunnen, David Dimmock, Gregory Enns, Giuseppe Gasparre,;Amy Goldstein, Iris Gonzalez, Katrina Gwinn, Sihoun Hahn, Richard H. Haas, Hakon Hakonarson, Michio Hirano, Douglas Kerr, Dong Li, Maria Lvova, Finley Macrae, Donna Maglott, Elizabeth McCormick, Grant Mitchell, Vamsi K. Mootha, Yasushi Okazaki,;Aurora Pujol, Melissa Parisi, Juan Carlos Perin, Eric A. Pierce, Vincent Procaccio, Shamima Rahman, Honey Reddi, Heidi Rehm, Erin Riggs, Richard Rodenburg, Yaffa Rubinstein, Russell Saneto, Mariangela Santorsola, Curt Scharfe,;Claire Sheldon, Eric A. Shoubridge, Domenico Simone, Bert Smeets, Jan A. Smeitink, Christine Stanley, Anu Suomalainen, Mark Tarnopolsky, Isabelle Thiffault, David R. Thorburn, Johan Van Hove, Lynne Wolfe, and Lee-Jun Wong
如果收集大量患者数据以增强准确序列变异注释、分析和解释的集体能力，则可以大大提高高度异质性疾病的基因组分析的成功率。事实上，分子诊断需要建立强大的数据资源，以实现数据共享，从而准确理解基因、变异和表型。“线粒体疾病序列数据资源（MSeqDR）联盟”是由联合线粒体疾病基金会推动的一项基层工作，旨在确定全球线粒体疾病临床和研究社区的特定基因组数据分析需求并对其进行优先排序。一个中央门户网站（https：mseqdr.org）有助于对来自疑似线粒体疾病的个体和家族的核和线粒体基因组的序列数据进行连贯的汇编、组织、注释和分析。该Web门户网站为用户提供了一套灵活且可扩展的资源，以安全、基于Web和用户友好的方式进行变异、基因和外显子组水平的序列分析。用户还可以选择与其他MSeqDR联盟成员甚至公众共享数据，无论是通过自定义注释跟踪还是通过使用方便的分布式注释系统（DAS）机制。提供了一系列数据可视化和分析工具，以便于用户询问和理解与线粒体生物学和疾病相关的基因组数据，以及最终的表型数据。目前可用的核和线粒体基因分析工具包括MSeqDR GBrowse实例，该实例托管优化的线粒体疾病和线粒体DNA（mtDNA）特定注释轨迹，以及MSeqDR位点特定数据库（LSDB），该数据库管理与线粒体疾病有关的1，300多个基因的变异数据和/或编码线粒体定位蛋白。MSeqDR与各种mtDNA数据分析工具集成，这些工具既独立又整合到在线外显子组级数据集管理和分析资源（GEM.app）中，该资源正在进行优化以支持MSeqDR社区的需求。此外，MSeqDR支持线粒体疾病表型和本体工具，并提供变异致病性评估功能，使社区审查，反馈和与公共ClinVar变异注释资源的集成。正在开发一个集中的基于网络的知情同意程序，并实施一个全球唯一标识符系统，以整合来自不同来源的关于特定个人的数据。基于社区的数据沉积到MSeqDR已经开始。未来的努力将提高纳入表型数据的能力，从而增强基因组数据分析。MSeqDR将填补生物信息学工具和集中知识的现有空白，这些工具和集中知识是使临床诊断和研究环境中的一系列股东能够有效解释核和mtDNA基因组数据所必需的。最终，MSeqDR致力于使全球线粒体疾病社区能够更好地定义和探索线粒体疾病。
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 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 1,300 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 disease.