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

项目总结

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.