Repositioning drugs for the treatment of small cell lung cancer

描述（由申请人提供）：许多形式的生物分子（例如，基因表达、遗传学、蛋白质组学）和临床（例如，临床生物标志物、药物靶点和适应症）与许多不同疾病有关的数据现在可以容易地从公开可用的数据储存库和知识库获得。现在有机会将这些数据整合到一个统一的，全球一致的人类疾病或疾病分类学的代表。这种疾病分类学将表达疾病如何在多个分子和临床轴上相互关联。在这次竞争性的更新中，我们计划对该项目进行重大扩建。我们计划从更新的公共数据库中捕获更多类型的分子测量数据。包括遗传和蛋白质测量将使疾病和疾病相似性的建模更加丰富，而不仅仅是mRNA测量。为了帮助将疾病中观察到的分子变化与遗传差异联系起来，我们计划将表达定量性状基因座（eQTL）纳入我们的疾病模型中，该模型是通过同时进行遗传和表达测量而构建的。为了扩大我们的疾病分类学在个性化医疗中的实用性，我们计划将更多的定量流行病学测量纳入疾病，并使用概率关系模型对疾病状态之间的转换进行建模。我们将比较我们的疾病分类与众所周知的ICD-10以及ICD-11，正在开发中。我们将开发新的可视化方法，在疾病分类中看到的复杂的边缘和节点。我们还计划在小细胞肺癌和免疫学与疾病的两个驱动生物项目中测试我们的疾病分类学，特别是为临床试验准备的新诊断和治疗方法。

DESCRIPTION (provided by applicant): Many forms of biomolecular (e.g., gene expression, genetics, proteomics) and clinical (e.g., clinical biomarkers, drug targets and indications) data pertaining to many different diseases are now readily available from publicly- available data repositories and knowledge-bases. There is now an opportunity to integrate these data into a unified, globally coherent representation of human disease, or nosology. Such a nosology would express how diseases are related to one another across multiple molecular and clinical axes. In this competitive renewal, we are planning a major expansion for this project. We plan to capture data from newer public repositories with more types of molecular measurements. Inclusion of genetic and protein measurements will enable a richer modeling of diseases and disease similarity, beyond mRNA measurements. To help link the molecular changes seen in disease to genetic differences, we plan to incorporate Expression Quantitative Trait Loci (eQTLs) into our disease models, built from simultaneous genetic and expression measurements. To expand the utility of our nosology in personalized medicine, we plan to incorporate more quantitative epidemiological measurements on disease, and to model transitions between disease states using probabilistic relational modeling. We will compare our nosology with the well-known ICD-10 as well as ICD-11, under development. We will develop novel visualization methods for the complex of edges and nodes seen in nosologies. We also plan to test our nosology in two Driving Biological Projects, in small cell lung cancer and immunology and disease, specifically yielding novel diagnostics and therapeutics ready for clinical trials.