Characterizing the genetic systems of autism through multi-disease analysis

通过多种疾病分析表征自闭症遗传系统

基本信息

批准号：
8402638
负责人：
Dennis Paul Wall
金额：
$ 50.33万
依托单位：
HARVARD MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-03-05 至 2013-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8402638
关键词：
Address Algorithms Autistic Disorder Behavior Behavioral Binding Bioinformatics Biological Process Boston Breathing Candidate Disease Gene Cells Characteristics Communities Companions Complex Data Databases Development Disease Ensure Foundations Genes Genetic Genetic Predisposition to Disease Genetic Variation Genomics Genotype Housing Imagery Individual Intention Internet Investigation Knowledge Light Link Maps Measurement Medical Libraries Methods Mining Molecular Molecular Profiling National Institute of Neurological Disorders and Stroke Navigation System Online Systems Pathway Analysis Pediatric Hospitals Phenotype Phylogenetic Analysis Pilot Projects Positioning Attribute Proteins Publishing Research Research Personnel Resources Role Sampling Site Solutions Source System Testing Text Therapeutic Intervention Trust Update Variant Vertebral column Weight Work abstracting base comparative data integration gene interaction genetic analysis genetic variant genome-wide grasp improved mRNA Expression medical schools member nervous system disorder open source protein protein interaction public health relevance relational database research study text searching tool trend web site

Address Algorithms Autistic Disorder Behavior Behavioral Binding Bioinformatics Biological Process Boston Breathing Candidate Disease Gene Cells Characteristics Communities Companions Complex Data Databases Development Disease Ensure Foundations Genes Genetic Genetic Predisposition to Disease Genetic Variation Genomics Genotype Housing Imagery Individual Intention Internet Investigation Knowledge Light Link Maps Measurement Medical Libraries Methods Mining Molecular Molecular Profiling National Institute of Neurological Disorders and Stroke Navigation System Online Systems Pathway Analysis Pediatric Hospitals Phenotype Phylogenetic Analysis Pilot Projects Positioning Attribute Proteins Publishing Research Research Personnel Resources Role Sampling Site Solutions Source System Testing Text Therapeutic Intervention Trust Update Variant Vertebral column Weight Work abstracting base comparative data integration gene interaction genetic analysis genetic variant genome-wide grasp improved mRNA Expression medical schools member nervous system disorder open source protein protein interaction public health relevance relational database research study text searching tool trend web site

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项目摘要

DESCRIPTION (provided by applicant): Autism is a complex disorder with a wide spectrum of phenotypes. Although it is clearly heritable, the molecular agents responsible remain elusive. More than 100 genes have been tied to Autism, each of which is involved in numerous different biological processes and in a variety of different molecular interactions. No single researcher can completely grasp the complexity of this Autism gene space, and perhaps for this reason, few genes have emerged as promising markers or targets for therapeutic intervention. Our plan is provide a way to grasp this complexity by shifting the focus from single genes to the entire genetic system of Autism. Thus, we will build the complete network of molecular interactions for all Autism candidate genes using bioinformatic methods that integrate multiple sources of genomic and bibliomic information. While this network will be a powerful enabler of new discoveries in Autism, it will not be enough to fully grasp the genetic underpinnings of the various behaviors indicative of the disorder. Hope for that however lies in the behavioral similarities between Autism and numerous other neurological disorders. These behavioral similarities suggest that there are common molecular mechanisms that if understood could help provide a clearer genotype-phenotype map of the Autism spectrum. Our plan is to capitalize on these similarities by conducting a comprehensive comparative analysis of the Autism network with the networks of more than 400 neurological disorders. Our work will result in a systems level view of Autism and its most similar neurological disorders that will not only help to see emergent trends that clarify the genetic basis of the spectrum, but will also help to prioritize known Autism candidates and reveal new candidates worthy of investigation. All of our work will be made freely accessible in a web-based tool that allows complete navigation through the Autism network and the networks of all other related neurological disorders. Wall & Kohane Abstract 1

描述（由申请人提供）：自闭症是一种具有广泛表型的复杂疾病。尽管显然是可以遗传的，但负责的分子剂仍然难以捉摸。超过100个基因与自闭症有关，每种基因都参与了许多不同的生物学过程和各种不同的分子相互作用。没有一个单一的研究人员能够完全掌握这种自闭症基因空间的复杂性，也许因此，很少有基因作为治疗干预的有希望的标记或靶标。我们的计划是通过将焦点从单个基因转移到整个自闭症遗传体系来掌握这种复杂性的方法。因此，我们将使用整合多种基因组和文献信息来源的生物信息学方法来为所有自闭症候选基因建立完整的分子相互作用网络。尽管该网络将是自闭症新发现的强大推动力，但它不足以完全掌握指示该疾病的各种行为的遗传基础。对此的希望在于自闭症与许多其他神经系统疾病之间的行为相似之处。这些行为相似性表明，有一些共同的分子机制，如果理解可以帮助提供自闭症谱系的更清晰的基因型 - 表型图。我们的计划是通过对400多个神经系统疾病的网络对自闭症网络进行全面的比较分析来利用这些相似性。我们的工作将导致自闭症及其最相似的神经系统疾病的系统级别的观点，这不仅将有助于看到阐明频谱遗传基础的新兴趋势，而且还将有助于优先考虑已知的自闭症候选者并揭示值得进行调查的新候选人。我们所有的工作都可以在基于Web的工具中自由访问，该工具允许通过自闭症网络和所有其他相关神经系统疾病的网络进行完整导航。 Wall＆Kohane摘要1