Transcriptome features of striated muscle aging and predictability of protein level changes.
Transcriptome features of striated muscle aging and predictability of protein level changes.
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DOI：
10.1039/d1mo00178g
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发表时间：
2021-10-11
期刊：
影响因子：
2.9
通讯作者：
Lau E
中科院分区：
文献类型：
--
作者：
Han Y;Li LZ;Kastury NL;Thomas CT;Lam MPY;Lau E
我们进行了总RNA测序和多组学分析，比较了年轻成年（4个月）与早期衰老（20个月）小鼠的骨骼肌和心肌，以研究横纹肌衰老的分子机制。我们观察到，老化的心肌和骨骼肌都引起先天免疫系统和线粒体途径的转录组学变化，但在细胞外基质过程中出现分歧。在个体基因水平上，我们在骨骼肌和心肌中鉴定了611个与年龄相关的特征，包括许多肌因子和心因子编码基因。由于RNA和蛋白质水平仅部分相关，我们认为准确反映其蛋白质对应物的差异表达转录本将是蛋白质组变化和扩展生理状态的更有价值的代理。我们应用计算数据分析工作流程来估计哪些转录组学变化更可能与使用大型蛋白质基因组学数据集的蛋白质水平调控相关。我们估计大约48%的衰老相关转录本能够很好地预测蛋白质水平（r ≥ 0.5）。与此同时，将所鉴定的衰老调节基因与公开的人类转录组学数据进行比较，结果显示，只有35-45%的所鉴定的基因在相应的人类组织中显示出年龄依赖性表达。因此，整合RNA-蛋白质相关性和人类保护跨数据源，我们提名了134个优先老化横纹肌签名，这些签名被预测与蛋白质水平密切相关，并且在人类中显示出年龄依赖性表达。这里的结果揭示了衰老如何在转录和蛋白质水平上重塑横纹肌基因表达的新细节。
We performed total RNA sequencing and multi-omics analysis comparing skeletal muscle and cardiac muscle in young adult (4 months) vs. early aging (20 months) mice to examine the molecular mechanisms of striated muscle aging. We observed that aging cardiac and skeletal muscles both invoke transcriptomic changes in the innate immune system and mitochondria pathways but diverge in extracellular matrix processes. On an individual gene level, we identified 611 age-associated signatures in skeletal and cardiac muscles, including a number of myokine and cardiokine encoding genes. Because RNA and protein levels correlate only partially, we reason that differentially expressed transcripts that accurately reflect their protein counterparts will be more valuable proxies for proteomic changes and by extension physiological states. We applied a computational data analysis workflow to estimate which transcriptomic changes are more likely relevant to protein-level regulation using large proteogenomics data sets. We estimate about 48% of the aging-associated transcripts predict protein levels well (r ≥ 0.5). In parallel, a comparison of the identified aging-regulated genes with public human transcriptomics data showed that only 35–45% of the identified genes show an age-dependent expression in corresponding human tissues. Thus, integrating both RNA-protein correlation and human conservation across data sources, we nominate 134 prioritized aging striated muscle signatures that are predicted to correlate strongly with protein levels and that show age-dependent expression in humans. The results here reveal new details into how aging reshapes gene expression in striated muscles at the transcript and protein levels.
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影响因子：
48
作者：
Huber W;Carey VJ;Gentleman R;Anders S;Carlson M;Carvalho BS;Bravo HC;Davis S;Gatto L;Girke T;Gottardo R;Hahne F;Hansen KD;Irizarry RA;Lawrence M;Love MI;MacDonald J;Obenchain V;Oleś AK;Pagès H;Reyes A;Shannon P;Smyth GK;Tenenbaum D;Waldron L;Morgan M
通讯作者：
Morgan M
影响因子：
64.5
作者：
Jiang L;Wang M;Lin S;Jian R;Li X;Chan J;Dong G;Fang H;Robinson AE;GTEx Consortium;Snyder MP
通讯作者：
Snyder MP
DOI：
10.1007/978-1-4939-3572-7_13
发表时间：
2016-01-01
期刊：
DATA MINING TECHNIQUES FOR THE LIFE SCIENCES
影响因子：
--
作者：
Dobin, Alexander;Gingeras, Thomas R.
通讯作者：
Gingeras, Thomas R.
影响因子：
64.5
作者：
Gillette, Michael A.;Satpathy, Shankha;Carr, Steven A.
通讯作者：
Carr, Steven A.
影响因子：
4.4
作者：
Hulstaert, Niels;Shofstahl, Jim;Perez-Riverol, Yasset
通讯作者：
Perez-Riverol, Yasset