Characterizing the genetic systems of autism through multi-disease analysis

描述(申请人提供)：自闭症是一种复杂的疾病，具有广泛的表型。尽管它显然是可遗传的，但负责的分子因素仍然难以捉摸。有100多个基因与自闭症有关，每个基因都参与了许多不同的生物过程和各种不同的分子相互作用。没有一位研究人员能够完全掌握自闭症基因空间的复杂性，也许正是因为这个原因，很少有基因成为治疗干预的有希望的标记或靶点。我们的计划是提供一种方法，通过将焦点从单基因转移到自闭症的整个遗传系统来理解这种复杂性。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，为所有自闭症候选基因建立完整的分子相互作用网络。虽然这个网络将成为自闭症新发现的强大推动者，但它还不足以完全掌握导致自闭症的各种行为的基因基础。然而，希望在于自闭症和许多其他神经疾病之间的行为相似之处。这些行为相似性表明，存在共同的分子机制，如果了解这些机制，可以帮助提供更清晰的自闭症谱系的基因-表型图谱。我们的计划是利用这些相似之处，对自闭症网络和400多个神经紊乱网络进行全面的比较分析。我们的工作将导致对自闭症及其最相似的神经疾病的系统水平的看法，这不仅将有助于看到阐明频谱遗传基础的新趋势，而且还将有助于优先考虑已知的自闭症候选人，并揭示值得研究的新候选人。我们的所有工作都将在一个基于网络的工具中免费访问，该工具允许在自闭症网络和所有其他相关神经障碍的网络中进行完整的导航。WALL&KOHANE摘要1

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