Multi-Omics Initiatives in MESA Study
Conducted by Jerome I. Rotter, the Multi-Ethnic Study of Atherosclerosis (MESA) explores multi-omics data integration, including genomics, transcriptomics, methylomics, and metabolomics. The study involves longitudinal sampling and aims to analyze changes in omics over time, link omics changes with phenotype change, and identify associations between multi-omics data and phenotypic variations in a diverse cohort. Examination of 4,620 MESA participants for a squared dataset creation, focusing on RNA sequencing, methylomics, and metabolomics, adds valuable insights into methodological practices and the significance of multiple time points in understanding biological pathways.
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Multi2 Multi-Omics in MESA (Multi-Ethnic Study of Atherosclerosis) By Jerome I. Rotter Genomics and Other Omics Initiatives MESA In Person Steering Committee April 20, 2017 1
TOPMed Multi-Omics Pilot 1. Assigned Scope of Work 1. 3000 RNA-Seq Broad (Gabriel), University of Washington (Nickerson) 2. 2,200 Methylomics Broad (Clish), Beth Israel (Gerszten) 3. 2,000 Metabolomics USC (Van den Berg) 2. Important Methodologic Questions - How samples stored - Extraction/preparation methods - Amounts of material needed for core assays 3. Value of Multiple Time Points 2
Final Considerations for the TOPMed Multi-Omics Pilot Questions to be addressed (in a multi-ethnic cohort) 1. Longitudinal sampling, change in omics over time 2. Association of omics change with phenotypic change 3. Multi-omics (genomic, transcriptomic, methylomic, metabolomic) associated with change in phenotypic Sample selection from 4,620 MESA TOPMed participants, creating a squared data set of 850 to 1000 sampled in MESA Exam 1 and Exam 5, with WGS Testing RNAseq (PBMCs), methylomics (whole blood), metabolomics (plasma) 4. QC for RNA extraction from cryo-preserved PBMC (Exam 1) and PBMC/monocytes (Exam 5), and for DNA extraction 3
MESA Multi-Omics Pilot, as of 9/30/2016 Study Design Diagram Metabolomics (Plasma) 850 a RNA Methyl-DNA (whole blood) 850 a 850 a Exam 1 (cryopreserved= PBMC s) (cryopreserved= PBMC s) (whole blood) (OH methyl)c 100 b +100 100 b 50 d 100 b (PBMC s) (whole blood) 850 a 850 a 100 b 850 a 100 b Exam 5 (PBMC s) (OH methyl)c ---- b +100 50 d 200 500 500 (PBMC s) (Monocytes) (T-cells) 34 33 33 (PBMC s) Total Samples Total Number of Subjects 3000 2200 2000 950 950 1000 a(Same 850 individuals). b(100 Chinese; selected with availability of sample in Exam 5 and Combio-Bio. Note, no Chinese available in Exam 5 epigenomics study). C(Same individuals within the 950, i.e. a plus b , and select for as many individuals as possible who have events). 4 d(50 additional individuals, the same individuals in Exam 1 and 5, with Combio-Bio data).
MESA Multi-Omics Pilot, as of 9/30/2016 Study Design Diagram Metabolomics (Plasma) 850 a RNA Methyl-DNA (whole blood) 850 a 850 a Exam 1 (cryopreserved= PBMC s) (cryopreserved= PBMC s) (whole blood) (OH methyl)c 100 b +100 100 b 50 d 100 b (PBMC s) (whole blood) 850 a 850 a 100 b 850 a 100 b Exam 5 (PBMC s) (OH methyl)c ---- b +100 50 d 200 500 500 (PBMC s) (Monocytes) (T-cells) 34 33 33 (PBMC s) Total Samples Total Number of Subjects 3000 2200 2000 950 950 1000 a(Same 850 individuals). b(100 Chinese; selected with availability of sample in Exam 5 and Combio-Bio. Note, no Chinese available in Exam 5 epigenomics study). C(Same individuals within the 950, i.e. a plus b , and select for as many individuals as possible who have events). 5 d(50 additional individuals, the same individuals in Exam 1 and 5, with Combio-Bio data).
MESA Multi-Omics Pilot, as of 9/30/2016 Study Design Diagram Metabolomics (Plasma) 850 a RNA Methyl-DNA (whole blood) 850 a 850 a Exam 1 (cryopreserved= PBMC s) (cryopreserved= PBMC s) (whole blood) (OH methyl)c 100 b +100 100 b 50 d 100 b (PBMC s) (whole blood) 850 a 850 a 100 b 850 a 100 b Exam 5 (PBMC s) (OH methyl)c ---- b +100 50 d 200 500 500 (PBMC s) (Monocytes) (T-cells) 34 33 33 (PBMC s) Total Samples Total Number of Subjects 3000 2200 2000 950 950 1000 a(Same 850 individuals). b(100 Chinese; selected with availability of sample in Exam 5 and Combio-Bio. Note, no Chinese available in Exam 5 epigenomics study). C(Same individuals within the 950, i.e. a plus b , and select for as many individuals as possible who have events). 6 d(50 additional individuals, the same individuals in Exam 1 and 5, with Combio-Bio data).
MESA Multi-Omics Pilot, as of 9/30/2016 Study Design Diagram Metabolomics (Plasma) 850 a RNA Methyl-DNA (whole blood) 850 a 850 a Exam 1 (cryopreserved= PBMC s) (cryopreserved= PBMC s) (whole blood) (OH methyl)c 100 b +100 100 b 50 d 100 b (PBMC s) (whole blood) 850 a 850 a 100 b 850 a 100 b Exam 5 (PBMC s) (OH methyl)c ---- b +100 50 d 200 500 500 (PBMC s) (Monocytes) (T-cells) 34 33 33 (PBMC s) Total Samples Total Number of Subjects 3000 2200 2000 950 950 1000 a(Same 850 individuals). b(100 Chinese; selected with availability of sample in Exam 5 and Combio-Bio. Note, no Chinese available in Exam 5 epigenomics study). C(Same individuals within the 950, i.e. a plus b , and select for as many individuals as possible who have events). 7 d(50 additional individuals, the same individuals in Exam 1 and 5, with Combio-Bio data).
MESA Multi-Omics Pilot, as of 9/30/2016 Study Design Diagram Metabolomics (Plasma) 850 a RNA Methyl-DNA (whole blood) 850 a 850 a Exam 1 (cryopreserved= PBMC s) (cryopreserved= PBMC s) (whole blood) (OH methyl)c 100 b +100 100 b 50 d 100 b (PBMC s) (whole blood) 850 a 850 a 100 b 850 a 100 b Exam 5 (PBMC s) (OH methyl)c ---- b +100 50 d 200 500 500 (PBMC s) (Monocytes) (T-cells) 34 33 33 (PBMC s) Total Samples Total Number of Subjects 3000 2200 2000 950 950 1000 a(Same 850 individuals). b(100 Chinese; selected with availability of sample in Exam 5 and Combio-Bio. Note, no Chinese available in Exam 5 epigenomics study). C(Same individuals within the 950, i.e. a plus b , and select for as many individuals as possible who have events). 8 d(50 additional individuals, the same individuals in Exam 1 and 5, with Combio-Bio data).
Current Status April, 2017 Pre-Pilot Pre-Pilots were conducted to assess sample preparation methods and sample utility (e.g. Exam 1 vs 5) - RNA Seq - Methylomics Pilot Metabolomics 2000 samples sent to Broad and Beth Israel Deacones Methylomics, thus far 1900 (of 2000) samples sent to USC RNA-Seq, thus far Over 2200 (of 3000) samples sent to Broad and UW/NWGC 9
Acknowledgements: TOPMed MESA Multi-Omics Pilot MESA MESA DCC (UW) Craig Johnson, Kayleen Williams MESA Central Lab (UV) Peter Durda, Elaine Cornell, Russ Tracy MESA Genetics (UF) Yongmei Liu, Tracey Young MESA Genetics (UA) Steve Rich MESA Genetics (LABioMed/Harbor) Kent Taylor, Jerry Rotter TOPMed DCC Cathy Laurie, Quenna Wong, Michael Bowers, Bruce Psaty IRC Tom Blackwell RNA Sequencing Broad Stacey Gabriel, Namrata Gupta, Kristin Ardlie, Francois Aguet, Katie Larsson UW NWGC Debbie Nickerson, Stephanie Krauter, Cris Frazar, Daniel McGoldrick, Colleen Davis, Josh Smith Methylomics USC David Van den Berg Metabolomics Beth Israel Deaconess Medical Center Robert Gerszten Broad Clary Clish NHLBI George Papanicolaou, Lorraine Silsbee, Panjaj Qashba, Rebecca Beer, Pothur Srinivas 10
