Colorado Clinical and Transational Sciences Institute

科罗拉多州临床和翻译科学研究所(CCTSI)的这一行政副刊的目标是通过完成对唐氏综合症患者的泛组学队列研究的试点阶段，显著加快唐氏综合症(DS)领域的临床和翻译科学的步伐。在共同研究员华金·埃斯皮诺萨博士的领导下，CCTSI与科罗拉多大学的Linda Crnic研究所唐氏综合症研究所合作，将使用本补充材料的资金来完成人口统计学和临床数据的提取，以及为300名已经登记参加Crnic Institute的人类三体项目的参与者生成关键组学数据集，该项目是一项具有深入临床元数据和匹配生物库的泛组学队列研究。利用已有的生物样本，本补编将能够创建丰富的多维数据集，并将通过研究人员门户网站公开访问，该门户网站目前处于开发的高级阶段。在本补充资料的支持下，该领域的研究人员将可以访问用户友好、直观的在线界面来研究以下数据集： ·300名研究参与者(其中200人患有DS)和100名年龄和性别匹配的典型对照的深度注释、未识别的人口统计数据和临床数据，涵盖了DS患者的整个寿命和更常见的一系列共病。 ·上面提到的所有300名参与者的大量白细胞转录数据。 ·所有300名参与者的5000多个表位的血浆蛋白质组学数据。 ·所有300名参与者的54种炎性细胞因子和趋化因子的血浆水平。 ·所有300名参与者的100个免疫细胞亚型的循环水平，由质量细胞仪定义。 ·通过质谱仪确定所有300名参与者的100+注释代谢物的血浆水平。 毫无疑问，这些努力将刺激该领域的额外活动，使研究人员能够快速测试和完善关于驱动DS共生条件的分子和细胞机制的假说。此外，所有人口统计数据和临床数据都将与DS-ConnectTM注册表兼容，所有组学数据也将通过公共储存库提供。 这项建议直接涉及INCLUDE项目的第二部分(即“通过队列研究对DS进行分子快照”)，完全符合父奖项关于推进临床和翻译科学的声明目标，同时也解决了NCATS的优先事项，即在翻译过程的所有阶段让患者和社区参与进来，在整个生命周期内将未得到充分服务的人群整合到翻译研究中，开发创新过程以提高翻译研究的质量和效率，并使用尖端信息学。

The goal of this Administrative Supplement to the Colorado Clinical and Translational Sciences Institute (CCTSI) is to significantly accelerate the pace of clinical and translational sciences in the field of Down syndrome (DS) by completing the pilot phase of a pan-omics cohort study of people with DS. Working in collaboration with the Linda Crnic Institute for Down Syndrome at the University of Colorado, under the leadership of co- Investigator Dr. Joaquin Espinosa, the CCTSI will use the funding from this supplement to complete abstraction of demographics and clinical data, as well as generation of key -omics datasets for 300 participants already enrolled in the Crnic Institute’s Human Trisome Project, a pan-omics cohort study with deep clinical metadata and a matching biobank. Using biological samples already available, this supplement will enable the creation of a rich multidimensional dataset, which will be made publicly accessible through a Researcher Gateway web portal that is currently in advanced stages of development. Enabled by this supplement, researchers in the field will have access to a user-friendly, intuitive, online interface to investigate the following datasets: • Deeply annotated, de-identified demographics and clinical data for 300 research participants, 200 of them with DS, and 100 age- and gender-matched typical controls, covering the entire lifespan and a wide range of co- morbidities more frequent in people with DS. • Transcriptomics data for bulk white blood cells for all 300 participants mentioned above. • Plasma proteomics data for 5000+ epitopes for all 300 participants. • Plasma levels of 54 inflammatory cytokines and chemokines for all 300 participants. • Circulating levels of 100 immune cell subtypes defined by mass-cytometry for all 300 participants. • Plasma levels of 100+ annotated metabolites identified by mass-spectrometry for all 300 participants. Undoubtedly, these efforts will stimulate additional activity in the field by enabling researchers to rapidly test and refine hypotheses about the molecular and cellular mechanisms driving co-occurring conditions in DS. Furthermore, all demographics and clinical data will be made compatible with the DS-ConnectTM registry, and all -omics data will be also made available through public repositories. This proposal, which directly addresses Component 2 of the INCLUDE project (i.e. ‘molecular snapshot of DS through a cohort study’), falls well within the stated goal of the parent award of advancing clinical and translational sciences, while also addressing NCATS priorities of engaging patients and communities in all phases of the translational process, integrating an underserved population in translational research across the lifespan, developing innovative processes to increase the quality and efficiency of translational research, and using cutting-edge informatics.