Enabling new discoveries in pharmacogenomics through a genomic date-driven nosolo

描述（由申请人提供）：在18世纪中期，卡尔·林奈发明了二项命名法，将生物分为等级或分类学。我们现代使用的DNA测序通过提供物种之间的定量距离测量，使物种在已建立的分类树中的位置重组成为可能。林奈也是系统疾病分类学的创始人之一。我们假设基因组数据、医学知识和结构化词汇已经发展到我们可以开始使疾病分类现代化的程度，就像DNA测序使分类学现代化一样。基于基因组学的疾病分类学的含义是多方面的。这样的分类将作为病理学连续尺度的开始，在那里我们可以量化一种疾病与另一种疾病的相似程度。长期以来，疾病都是根据共同的症状来组织的，最近，在已知的病理生理学中也有共同的症状。有了基于基因组学的疾病分类学，我们可以扩展古老的分类学方法，通过对许多常见疾病的基因表达进行定量测量，将疾病联系起来。此外，基因组分类学可用于确定新的治疗机会。本提案的中心假设是：(1)在基因组实验领域存在足够的数据，可以形成基因组数据驱动的疾病分类学；(2)目前最大的疾病分类学，SNOMED-CT，类似于基因组分类学；(3)基因组分类学可以发现新的可测试的药物基因组学关系。为了建立能够实现这些目标的工具和数据库，我们建议在国家生物医学本体中心（NCBO, PI: Mark Musen）和药物遗传和药物基因组知识库（PharmGKB, PI: Russ Altman）之间开展一项新的合作。该项目汇集了生物信息学、医学信息学、本体论和药物基因组学方面的研究人员，他们在生物信息学方面有长期的方法贡献记录，以及由美国国立卫生研究院路线图资助的7个国家生物医学计算中心中的3个的首席研究员组成的咨询委员会。开发一种新的方法来创建第一个药物基因组分类，并应用这种分类学来发现药物和基因之间的新关系。

DESCRIPTION (provided by applicant): In the mid 1700s, Carl Linnaeus devised the binomial nomenclature to classify living things into a hierarchy, or taxonomy. Our modern day use of DNA sequencing has enabled the reorganization of the position of species within established taxonomical trees by providing a quantitative distance measure between species. Linnaeus was also the co-founder of systematic nosology, or the classification of disease. We hypothesize that genomic data, medical knowledge, and structured vocabularies have advanced to the point that we can begin to modernize the classification of disease, similar to how DNA sequencing has modernized taxonomy. The implications of a genomics-based nosology are many. Such a classification would serve as the beginnings of a continuous scale for pathology, where we could quantitate how similar one disease is to another. Diseases have long been organized based on common symptoms, and more recently, commonalities in known pathophysiology. With a genomics-based nosology, we can extend the age-old approach of taxonomy to relate diseases by the quantitative measurements of gene expression now available for many common disorders. In addition, a genomic nosology could be used to identify new therapeutic opportunities. The central hypotheses for this proposal are (1) sufficient data in the realm of genomic experiments exists to enable the formation of a genomic-data driven nosology, (2) that the largest current disease nosology, SNOMED-CT, resembles a genomic nosology, and (3) a genomic nosology can enable the discovery of novel testable pharmacogenomic relations. To build the tools and databases that address these aims, we are proposing a novel collaboration between the National Center for Biomedical Ontology (NCBO, PI: Mark Musen) and the Pharmacogenetic and pharmacogenomic Knowledge Base (PharmGKB, PI: Russ Altman). This project brings together researchers in bioinformatics, medical informatics, ontology's, and pharmacogenomics with a long track record of methodological contributions to bioinformatics, together with an advisory board with Principal Investigators from 3 of the 7 NIH-roadmap funded National Centers for Biomedical Computing, to develop a novel methodological approach to create the first genomic classification of medicine and apply this nosology to discover new relations between drugs and genes.