Fig 1: Pseudotime Analysis Temporally Orders the Core Set of 60 Functionally Similar Genes DE in Both the Bulk and Single-Cell RNA-Seq between Control and PD GBA-N370S Patients(A) Refined transcriptomic disease axis analysis of the core gene set of 60 genes. The control-disease single-cell transcriptomic axis was re-inferred with the 60 genes alone using a parametric factor analysis model that associated each gene with a point along the axis at which it was upregulated or downregulated.(B) The phenotypic linkage network demonstrates a higher functional similarity of the 60-gene set with each other compared to a background control set (p < 2.2e-16). This higher functional similarity was also identified between the 60-gene set and a group of known PD loci, compared to a background control set (p = 8.52e-08). The high functional similarity of PD genes to each other is used as a positive control.(C) Along the axis of disease, the downregulation of HDAC4-controlled genes (PRKCB, RTN1, ATP1A3, and TSPAN7) at 22 DIV precedes the upregulation of ER stress genes (ERO1A, FKBP9, and PDI) at 38 DIV. Data are represented as mean ± SD (*p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001). The locations of the HDAC4 and ER genes analyzed from the core 60 set are marked on (A).