Trans-omics integration of multi-omics studies for male osteoporosis

项目摘要 COVID-19是一场全球性大流行病，导致医疗和社会经济危机。有很大的变化， SARS-CoV-2感染的个体反应的症状/结果。一个关键问题是： （衰老/环境/医疗/药物/生活方式/饮食/宏基因组）和内在（例如，基因组/转录本- 组学/代谢组学）因素是COVID-19易感性、严重程度和结局个体差异的基础？ 我们建议在此及时解决上述问题。我们将利用现有的1，055个独特的队列 高加索人和非洲裔美国人招募/表型分析/分析与尖端的多组学技术， 大新奥尔良（GNO）地区，用于我们正在进行的U19母项目（U19 AG 055373）和更大的LOS （路易斯安那州骨质疏松症研究）队列，> 16，400名受试者（所有种族，男女，年龄17-97岁）。 GNO是美国受COVID-19影响最严重的地区之一。我们处于一个独特的位置，以满足以下要求： 受试者招募和数据收集：从U19和LOS队列中，我们将招募>400名受试者， COVID-19和匹配的对照，均具有确认的感染状态，并从他们身上获得所需的生物标本。 我们还将招募和收集600名COVID-19患者的表型信息和生物标本， 奥克斯纳卫生系统，路易斯安那州最大的医疗保健系统。对于U19和LOS队列，我们将在一个 利用其现有的感染前（基线）多组学特征的独特地位。对于所有被招募的 COVID 19受试者，我们将评估他们感染后的多组学特征，以追求以下目标： 目的1：确定人类宿主和肠道微生物组中的潜在基因/细菌种类/分子途径 通过对COVID-19感染者的比较多组学分析， 具有感染前多组学数据的受试者及其匹配对照。 目的2：通过以下方式确定与疾病严重程度相关的衰老/环境/遗传/分子因素： 比较个体状况（年龄、性别、种族、饮食、医疗、药物、生活方式等）和感染后 在> 1，000名具有各种疾病严重程度/结果的COVID 19感染受试者中的多组学特征。 目的3：通过比较感染前（基线），确定疾病严重程度的潜在致病分子因素 COVID 19感染者的多组学特征和多组学特征的变化（感染后与感染前） 具有各种疾病严重程度/结局的受试者。 目的4：对药物再利用进行生物信息学分析，以识别现有药物， 治疗COVID-19，基于从多组学数据中获得的人体体内分子机制。 这项研究将获得关于COVID个体差异的基本机制的重要信息， 19易感性/严重性/结果，并为个性化药物（特别是针对各种 年龄组/医疗条件）使用现有药物作为紧急应对措施。获得的数据/样本/队列将 在未来的后续研究中，对于研究COVID-19对健康，特别是衰老的长期影响非常宝贵。

PROJECT SUMMARY COVID-19 is a global pandemic, causing a medical and social-economic crisis. There are large variations of symptoms/outcomes in individual responses to SARS-CoV-2 infection. A key question is: what extrinsic (aging/environmental/medical/medication/lifestyle/diet/metagenomic) and intrinsic (e.g., genomic/transcript- omic/metabolomic) factors underlie individual variation in COVID-19 susceptibility, severity and outcomes? We propose to timely address the above question here. We will leverage on an existing unique cohort of 1,055 Caucasian and African American recruited/phenotyped/profiled with cutting-edge multi-omics technologies in the Greater New Orleans (GNO) area for our ongoing U19 parent project (U19AG055373) and the larger LOS (Louisiana Osteoporosis Study) cohort with >16,400 subjects (all ethnicities, both sexes, aged 17-97 years old). GNO is one of the hardest hit areas in US by COVID-19. We are in a unique position to fulfill the following: Subject Recruitment and Data Collection: From the U19 and LOS cohorts, we will recruit >400 subjects with COVID-19 and matched controls, all with confirmed infection status, and obtain the needed biospecimens from them. We will also recruit and collect phenotypic information and biospecimens from 600 COVID-19 patients through Ochsner Health System, Louisiana’s largest healthcare system. For the U19 and LOS cohorts, we will be in a unique position to leverage their existing pre-infection (baseline) multi-omics profiles. For all the recruited COVID19 subjects, we will assess their post-infection multi-omics profiles, to pursue the following: Aim 1: Identify potential genes/bacteria species/molecular pathways in human hosts and gut microbiome that influence susceptibility of COVID-19, by comparative multi-omics analyses of those COVID19 infected subjects with pre-infection multi-omics data and their matched controls. Aim 2: Identify aging/environmental/genetic/molecular factors associated with disease severity, by comparing individual conditions (aging, gender, ethnicity, diet, medical, medication, lifestyle, etc.) and post-infection multi-omics profiles among >1,000 COVID19 infected subjects with various disease severities/outcomes. Aim 3: Identify potential causal molecular factors for disease severity, by comparing the pre-infection (baseline) multi-omics profiles and changes in multi-omics profiles (post- vs. pre-infection) among the COVID19 infected subjects with various disease severities/outcomes. Aim 4: Perform bioinformatic analyses for drug repurposing to identify existing drugs that would effectively treat COVID-19, based on the molecular mechanisms gained in vivo in humans from the multi-omics data. This study will gain significant information on the fundamental mechanisms underlying individual variation in COVID- 19 susceptibility/severity/outcomes, and pave the way for personalized medicine (especially those targeting various age groups/medical conditions) using existing drugs as urgent responses. The data/samples/cohorts obtained will be invaluable for studying the long-term effects of COVID-19 on health, especially aging, in future follow-up studies.