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Fig. 1 | Molecular Autism

Fig. 1

From: Translatome analysis of tuberous sclerosis complex 1 patient-derived neural progenitor cells reveals rapamycin-dependent and independent alterations

Fig. 1

TSC1-associated alterations in mRNA abundance and translation. A Overview of the polysome-profiling approach in NPCs to identify TSC1-associated changes in gene expression. B Overview of modes for gene expression alterations identified by anota2seq where changes in mRNA levels and their ribosome association are indicated by curled lines (mRNA) and gray circles (ribosomes), respectively (left). Scatter plot from anota2seq analysis comparing polysome-associated to cytosolic mRNA log2 fold changes for the TSC1−/− NPC versus TSC1+/+ NPC comparison (right). Genes identified as differentially regulated by anota2seq (see “Methods” section for applied thresholds) in each gene expression mode are visualized in the scatter, and the total number of genes is indicated in brackets. C Kernel densities of p values or FDRs (from anota2seq analysis) for the comparison of TSC1−/− versus TSC1+/+ NPCs. Densities are shown for analysis of polysome-associated RNA, cytosolic RNA, translation and offsetting. D Scatter plot of log2 fold changes comparing TSC1−/− versus TSC1+/+ NPCs estimated using NanoString nCounter assays. Each gene is represented by an arrow where the start of the arrow shows the fold changes estimated by RNA sequencing (i.e., B) and the end of the arrow indicates the fold change obtained by NanoString nCounter assays. E Scatter plot from anota2seq analysis comparing polysome-associated to cytosolic mRNA log2 fold changes for the TSC1−/− NPC versus TSC1+/+ NPC comparison (left panel) showing genes randomly selected for validation by RT-qPCR (purple) relative to background (gray). The right panel indicates changes in translational efficiencies (i.e., polysome-associated mRNA normalized to cytosolic mRNA) according to RT-qPCR for the same genes. F Gene-set enrichment analysis for proteins encoded by mRNAs whose translation increase or decrease in TSC1−/− versus TSC1+/+ NPCs. Each node corresponds to a process or pathway and edges connect nodes that were identified from overlapping genes (see “Methods” section for details)

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Molecular Autism

ISSN: 2040-2392