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.