Journal: Molecular Systems Biology
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Abbreviation
Mol Syst Biol
Publisher
Wiley-Blackwell
3 results
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Publications 1 - 3 of 3
- Small hairpin RNA as a small molecule sensorItem type: Journal Article
Molecular Systems BiologyBenenson, Yaakov (2008) - Quantitative variability of 342 plasma proteins in a human twin populationItem type: Journal Article
Molecular Systems BiologyLiu, Yansheng; Buil, Alfonso; Collins, Ben C.; et al. (2015)The degree and the origins of quantitative variability of most human plasma proteins are largely unknown. Because the twin study design provides a natural opportunity to estimate the relative contribution of heritability and environment to different traits in human population, we applied here the highly accurate and reproducible SWATH mass spectrometry technique to quantify 1,904 peptides defining 342 unique plasma proteins in 232 plasma samples collected longitudinally from pairs of monozygotic and dizygotic twins at intervals of 2–7 years, and proportioned the observed total quantitative variability to its root causes, genes, and environmental and longitudinal factors. The data indicate that different proteins show vastly different patterns of abundance variability among humans and that genetic control and longitudinal variation affect protein levels and biological processes to different degrees. The data further strongly suggest that the plasma concentrations of clinical biomarkers need to be calibrated against genetic and temporal factors. Moreover, we identified 13 cis‐SNPs significantly influencing the level of specific plasma proteins. These results therefore have immediate implications for the effective design of blood‐based biomarker studies. - Inferring causal metabolic signals that regulate the dynamic TORC1-dependent transcriptomeItem type: Journal Article
Molecular Systems BiologyOliveira, Ana P.; Dimopoulos, Sotiris; Busetto, Alberto G.; et al. (2015)Cells react to nutritional cues in changing environments via the integrated action of signaling, transcriptional, and metabolic networks. Mechanistic insight into signaling processes is often complicated because ubiquitous feedback loops obscure causal relationships. Consequently, the endogenous inputs of many nutrient signaling pathways remain unknown. Recent advances for system‐wide experimental data generation have facilitated the quantification of signaling systems, but the integration of multi‐level dynamic data remains challenging. Here, we co‐designed dynamic experiments and a probabilistic, model‐based method to infer causal relationships between metabolism, signaling, and gene regulation. We analyzed the dynamic regulation of nitrogen metabolism by the target of rapamycin complex 1 (TORC1) pathway in budding yeast. Dynamic transcriptomic, proteomic, and metabolomic measurements along shifts in nitrogen quality yielded a consistent dataset that demonstrated extensive re‐wiring of cellular networks during adaptation. Our inference method identified putative downstream targets of TORC1 and putative metabolic inputs of TORC1, including the hypothesized glutamine signal. The work provides a basis for further mechanistic studies of nitrogen metabolism and a general computational framework to study cellular processes.
Publications 1 - 3 of 3