Defining the consequences of genetic variation on a proteome-wide scale

Genetic variation governs protein expression through both transcriptional and post-transcriptional processes. To investigate this relationship, we combined a multiplexed, mass spectrometry-based method for protein quantification with an emerging mouse model harboring extensive genetic variation from 8 founder strains. We collected genome-wide mRNA and protein profiling measurements to link genetic variation to protein expression differences in livers from 192 Diversity Outcross mice. Illumina 100bp single-end liver RNA-seq from 192 male and female Diversity Outbred 26-week old mice raised on standard chow or high fat diet. Each sample was sequenced in 2x technical replicates across multiple flowcells. Samples were randomly assigned lanes and multiplexed at 12-24x.遗传变异通过转录及转录后过程调控蛋白质表达。为探究该调控关系，我们将基于质谱的多重蛋白质定量方法，与一种携带来自8个创始品系广泛遗传变异的新型小鼠模型相结合。我们针对192只多样性远交（Diversity Outcross）小鼠的肝脏组织，开展全基因组范围的mRNA与蛋白质表达谱检测，以关联遗传变异与蛋白质表达差异。本研究对192只饲喂标准饲料或高脂饲料的26周龄多样性远交（Diversity Outbred）雌雄小鼠的肝脏组织，开展了Illumina 100bp单端RNA测序（RNA-seq）。每份样本在多个测序流动池上完成了2次技术重复测序。样本被随机分配至测序泳道，并以12-24倍多重度进行样本混合测序。