Multiomic profiling of the liver across diets and age in a diverse mouse population
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Multiomic profiling of the liver across diets and age in a diverse mouse population. / Williams, Evan G.; Pfister, Niklas; Roy, Suheeta; Statzer, Cyril; Haverty, Jack; Ingels, Jesse; Bohl, Casey; Hasan, Moaraj; Čuklina, Jelena; Bühlmann, Peter; Zamboni, Nicola; Lu, Lu; Ewald, Collin Y.; Williams, Robert W.; Aebersold, Ruedi.
I: Cell Systems, Bind 13, Nr. 1, 2022, s. 43-57, e1-6.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Multiomic profiling of the liver across diets and age in a diverse mouse population
AU - Williams, Evan G.
AU - Pfister, Niklas
AU - Roy, Suheeta
AU - Statzer, Cyril
AU - Haverty, Jack
AU - Ingels, Jesse
AU - Bohl, Casey
AU - Hasan, Moaraj
AU - Čuklina, Jelena
AU - Bühlmann, Peter
AU - Zamboni, Nicola
AU - Lu, Lu
AU - Ewald, Collin Y.
AU - Williams, Robert W.
AU - Aebersold, Ruedi
N1 - Publisher Copyright: © 2021 Elsevier Inc.
PY - 2022
Y1 - 2022
N2 - We profiled the liver transcriptome, proteome, and metabolome in 347 individuals from 58 isogenic strains of the BXD mouse population across age (7 to 24 months) and diet (low or high fat) to link molecular variations to metabolic traits. Several hundred genes are affected by diet and/or age at the transcript and protein levels. Orthologs of two aging-associated genes, St7 and Ctsd, were knocked down in C. elegans, reducing longevity in wild-type and mutant long-lived strains. The multiomics data were analyzed as segregating gene networks according to each independent variable, providing causal insight into dietary and aging effects. Candidates were cross-examined in an independent diversity outbred mouse liver dataset segregating for similar diets, with ∼80%–90% of diet-related candidate genes found in common across datasets. Together, we have developed a large multiomics resource for multivariate analysis of complex traits and demonstrate a methodology for moving from observational associations to causal connections.
AB - We profiled the liver transcriptome, proteome, and metabolome in 347 individuals from 58 isogenic strains of the BXD mouse population across age (7 to 24 months) and diet (low or high fat) to link molecular variations to metabolic traits. Several hundred genes are affected by diet and/or age at the transcript and protein levels. Orthologs of two aging-associated genes, St7 and Ctsd, were knocked down in C. elegans, reducing longevity in wild-type and mutant long-lived strains. The multiomics data were analyzed as segregating gene networks according to each independent variable, providing causal insight into dietary and aging effects. Candidates were cross-examined in an independent diversity outbred mouse liver dataset segregating for similar diets, with ∼80%–90% of diet-related candidate genes found in common across datasets. Together, we have developed a large multiomics resource for multivariate analysis of complex traits and demonstrate a methodology for moving from observational associations to causal connections.
KW - aging
KW - causal inference
KW - gene-by-environment interaction
KW - genetic reference population
KW - GxE
KW - liver
KW - multiomics
KW - multivariate analysis
KW - network biology
KW - proteomics
KW - time course
U2 - 10.1016/j.cels.2021.09.005
DO - 10.1016/j.cels.2021.09.005
M3 - Journal article
C2 - 34666007
AN - SCOPUS:85122747917
VL - 13
SP - 43-57, e1-6
JO - Cell Systems
JF - Cell Systems
SN - 2405-4712
IS - 1
ER -
ID: 304515902