Integrating innovative technologies for genotyping and phenotyping in stratified medicine

与疾病如何发展和进展或对治疗的反应相关的机制并不相同，而是取决于人类受试者。被定义为分层医学的策略是基于对具有不同疾病机制或对治疗有特定反应的患者进行分组，以便确定和应用对特定患者群体有效的治疗方法。这提供了快速确定或改变患者管理和早期治疗的机会，为患者提供了最大的利益。为实现这一目标，有必要将细胞和尿液等生物液体的化学成分数据与年龄、性别和其他特征相关的数据结合起来，以提供关于如何诊断疾病、快速确定正确治疗方法和根据复发风险监测患者的信息。这一战略的目的是提供一个针对个别病人的监测和治疗系统。我们建议在伯明翰建立世界领先的临床和研究环境，通过主要的基础设施投资创建西米德兰兹分层医学创新和翻译设施，与一个雄心勃勃的研究计划相一致，这将提高我们的机械知识以及诊断和临床能力。研究将特别侧重于免疫介导的炎症性疾病（如关节炎和肝病）和血癌（如白血病），这两种疾病在英国的发病率正在上升，部分原因是人口老龄化。我们的跨学科研究计划将侧重于每种疾病中不同细胞类型的分子研究和特征以及患者相关的分子变化。它将开发和测试多种诊断方法的整合，包括大规模细胞术、代谢表型、单细胞基因组学和功能基因组学。我们将获得关于疾病如何发展和进展的机制的新见解，以及他们对治疗的反应，目的是通过建立分层诊断和靶向治疗来推动创新发现进入临床实践。这不仅将建立在当地投资的基础上，如2400万英镑的转化医学研究所（由政府与我们的NHS合作伙伴伯明翰大学医院共同资助）和新的410万英镑的计算生物学中心，而且还将同时建立在新技术上的国家投资，如CyTOF细胞分选和最近的MRC-NIHR国家表型中心，我们正在与所有这些人合作，以实现国家分层医学研究能力的逐步改变。

The mechanisms associated with how a disease develops and progresses, or response to a treatment, are not identical but are dependent on the human subject. The strategy defined as stratified medicine is based on grouping patients with distinct mechanisms of disease, or particular responses to treatments in order to identify and apply treatments that are effective for particular groups of patients. This provides the opportunity to rapidly define or alter patient management and treatments early, providing a maximum benefit to the patient. To achieve this, it is necessary to combine data on the chemical composition of cells and biofluids like urine, with data related to age, gender and other characteristics to provide information on how to diagnose a disease, to identify the correct treatment rapidly, and to monitor patients based on risk of relapse. The aim is this strategy is to deliver a system of monitoring and treatment which is tailored towards the individual patient. We are proposing to build upon the world-leading clinical and research environment within Birmingham by creating a West Midlands Stratified Medicine Innovation & Translation Facility through major infrastructure investment, aligned to an ambitious research programme which will enhance our mechanistic knowledge as well as diagnostic and clinical capabilities. Research will particularly focus on immune-mediated inflammatory diseases (e.g. arthritis and liver disease) and blood cancers (e.g. leukaemia), which are increasing in prevalence in the UK, partly as a consequence of an aging population. Our interdisciplinary research programme will focus on the molecular study and characterisation of different cell types within each disease and the associated molecular changes in the patient. It will develop and test the integration of multiple diagnostic strands including methods called mass cytometry, metabolic phenotyping and single-cell genomics and functional genomics. We will obtain new insight into the mechanisms of how diseases develop and progress, and their responsiveness to treatment, with the aim to drive innovative discoveries into clinical practice through the establishment of stratified diagnostics and targeted therapies. This will not only build on local investments such as the £24m Institute for Translational Medicine (co-funded by government, along with our NHS partners University Hospitals Birmingham) and the new £4.1m Centre for Computational Biology, but also concurrent national investments in new technology such as CyTOF cell sorting and the recent MRC-NIHR National Phenome Centre, all of whom we are collaborating with to enable a step-change in national capabilities in stratified medicine research.