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Multiplexed assays of variant effects contribute to a growing genotypephenotype atlas

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We modeled the aging effects using the following data: expression fold changes of enzymes and transporters from the Tabula Muris Senis (TMS) dataset (26, 27) applied as scaling factors to levels of corresponding enzymes and transporters scaled initial concentrations of blood glucose, lactate, and -hydroxybutyrate according to the literature data on difference in their levels in aging (approximation, because effect size depends on the literature source) total NAD + and NADH concentration pool scaling (approximation), because it decreases in aging according to qualitative literature synaptic glutamate release pool (approximation, but synaptic input is set as the same for comparability of the results) scaling of reducing equivalents shuttles between cytosol and mitochondria: the NADH shuttle is a generalized rate equation based on the activity of multiple enzymes of malate-aspartate and glycerol-phosphate shuttles, for which we followed the literature to model it (24)

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