Smokescreen Translational (TL) Analysis Platform

项目摘要 烟草引起的疾病仍然是最大的潜在可改变的死亡原因。战略以减少 吸烟率包括开发更有效的戒烟治疗方法。尼古丁代谢 和依赖性是吸烟行为的预测因子，包括对戒烟治疗的反应。 这个第二阶段项目的目标是开发尼古丁代谢、尼古丁依赖的预测模型， 和戒烟的临床和基因数据。一套优化的模型将在 “Smokescreen®翻译（TL）分析平台”，并应用于寻求治疗的临床队列 吸烟者。 我们之前设计了Smokescreen®GTA，这是一种全基因组阵列，可以深入捕获 超过1，000个成瘾基因，包括尼古丁代谢和尼古丁依赖的最重要位点。 我们已经鉴定了艾德多种代谢和调节基因，这些基因用相对较少的标记物就可以预测一种代谢和调节基因。 个体的尼古丁代谢活性。我们将使用现有的队列和吸烟者的临床治疗试验 为了发现和测试综合模型，目的是提供尼古丁代谢的估计， 依赖性和终止概率。这些模型将结合祖先，临床，基因组和社会瓦里， 能够最大限度地预测戒烟。我们将开发一种用于基因分型的紧凑型实验室检测方法 带有特定标记的DNA样本和用于分析临床和基因组数据的软件。Smokescreen®TL将 在临床护理中对吸烟者进行验证。结果将以灵活的报告格式提供。最后， Smokescreen®TL将可供有兴趣帮助寻求治疗的医疗保健提供者使用 吸烟者戒烟。

Project Summary Tobacco-attributable disease remains the largest potentially modifiable cause of mortality. Strategies to reduce smoking prevalence include developing more effective smoking cessation treatments. Nicotine metabolism and dependence are predictors of smoking behaviors, including response to smoking cessation treatments. The goal of this Phase II project is to develop prediction models of nicotine metabolism, nicotine dependence and smoking cessation from clinical and genomic data. An optimized set of models will be implemented in the “Smokescreen®Translational (TL) Analysis Platform”, and applied to clinical cohorts of treatment-seeking smokers. We have previously designed Smokescreen®GTA, a genome-wide array that deeply captures variation in over 1,000 addiction genes, including the most important loci for nicotine metabolism and nicotine dependence. We have identified multiple metabolic and regulatory genes, that with relatively few markers, can predict an individual's nicotine metabolic activity. We will use existing cohorts and a clinical treatment trial of smokers to discover and test integrated models with the goal of providing estimates of nicotine metabolism, nicotine dependence and cessation probability. These models will incorporate ancestry, clinical, genomic and social vari- ables to maximize prediction of smoking cessation. We will develop a compact laboratory assay for genotyping DNA samples with specific markers and software to analyze clinical and genomic data. Smokescreen®TL will be validated in smokers in clinical care. The results will be delivered in flexible reporting formats. Ultimately, Smokescreen®TL will be available for use by health care providers interested in helping treatment seeking smokers quit.