Submitted thesis 03/02/2021 - now has corrections - resubmission deadline Nov-2022

提交的论文03/02/2021-NOW有更正-重新提交截止日期11月-2022发现旧药物的新适应症(重新用途)所需的信息可能来自不同的来源。药物不良事件的电子健康记录和数据库将提供有关“现实生活”药物使用的信息。Gwas将提供有关基因-表型关联的信息。从生物学上，我们可能知道是什么编码了什么蛋白质，以及这些蛋白质参与的一些生物学途径。从实验中，我们知道每个分子(药物)都附着在(或可能附着)什么蛋白质上。所有这些信息都存储在不同的数据库中，而且数据往往是不可链接的，因为我们在所有数据库中并没有关于同一个人的信息。我们将提取相关关联的信息，并以一种方式组合这些信息，以便我们能够提供可衡量的证据或对某种药物对特定疾病的潜在影响的“信念”(即提供关于疾病-基因-蛋白质-药物的特定联系的证据)。这里的关键问题是定义一种表示每条信息中证据或信念的程度的方法，并提出逻辑上一致的规则来组合它们。拨款552247取代了旧的章节拨款513157

Submitted thesis 03/02/2021 - now has corrections - resubmission deadline Nov-2022The information needed for the discovery of a new indication of an old drug (repurposing) might come from different sources. Electronic health records and databases of drugs adverse events will give information about "real life" use of drugs. GWAS will provide information on gene-phenotype association. From biology we might know what code what proteins, and some of the biological pathways in which these proteins participate. From experiments we know to what proteins each molecule (drug) attaches (or might attach to). All these pieces of information are stored in different databases, and often the data is not linkable, in the sense that we do not have the information for the same individual in all the databases.We will extract information on relevant associations and combine this information in such a way that we can provide a measurable degree of evidence or "belief" on the potential effect of a drug on a particular disease (i.e. provide evidence on a particular connection of disease-gene-protein-drug). The key problem here is to define a way of representing the degree of evidence or belief in each of the pieces of information, and come up with logically consistent rules to combine them.Grant 552247 replaces old CHAPTER grant 513157