Core liver homeostatic co-expression networks are preserved between mouse and human but respond to perturbations in an organism- and disease-specific manner

Chronic complex diseases are difficult to model in animals and to reproducibly translate the findings to human disease. We argued that organs have core networks that are preserved between species and are predictably altered when homeostasis is disrupted. We altered hepatic homeostasis in mice by dietary challenge and compared the liver transcriptome to that in metabolic associated fatty liver disease (MAFLD) and liver cancer. Total liver RNA was extracted using RNAeasy (Qiagen). RNA purity and integrity were confirmed using an Agilent Bioanalyzer. Libraries were prepared from 100 ng total RNA (TruSeq Stranded Total RNA kit, Illumina) and singled-ended sequencing performed on the Illumina HiSeq 2500 using bar-coded multiplexing and a 50 bp read length, yielding a median of 10.7 M reads per sample. Read alignment and junction finding was accomplished using STAR using the ‘quantmode GeneCounts’ option and an Ensemble mm10 annotation in GTF format.