Visium SPG AD project (n = 10) using Visium Spatial Proteogenomics (Visium-SPG) on dissections from the inferior temporal cortex (ITC) from Alzheimer's disease cases and controls.
[x] Confirm with Leo logcounts vs log(counts) vs expression(logcounts)
Nat Neuro
PsychENCODE
currently on our Visium_SPG_AD
[x] Confirm with Leo the figure captions about the Harmony-based batch correction.
Figure S10. Harmony-based batch correction of Visium SRT data
(A) UMAP representation of Visium spots aggregated across 10 tissue sections illustrates the effects of donor and technical variability, colored by sample IDs.
(B) Harmony was employed to minimize donor effects and technical variations across multiple Visium-SPG experiments.
[x] Confirm with Leo the figure captions about the volcano plots.
Fig.2 Identification of transcriptomic signatures in local microenvironments harboring AD-related neuropathology
(D) Volcano plots depicting differentially expressed genes (DEGs) between Aβ pathology (Aβ) or adjacent Aβ pathology (Next_Aβ) versus rest of pathological categories. Each dot represents a DEG, plotted with its fold change (x-axis) and p-value (y-axis) for the magnitude and significance of the difference in gene expression. The dashed line represents a p-value threshold (<0.01), with DEGs below the line considered not significant (gray, Not sig.) Significant DEGs that passed the FDR threshold (>0.1) were labeled red and classified by their enrichment (>rest) and depletion (<rest) in gene expression according to the ‘enrichment’ model.
Figure S12. Inspecting biological functions and pathways of AD-associated microenvironments
A) Volcano plots depicting DEGs in 5 other AD-related pathological categories based on the enrichment model. Each dot represents a DEG, plotted with its fold change (x-axis) and p-value (y-axis) for the magnitude and significance of the difference in gene expression, respectively. No DEGs (gray) passed the p-value and FDR threshold for these 5 pathological categories.
[ ] Confirm with Leo the figure captions about the GSEA results
Figure S13. Enrichment of neurodegeneration- and dementia-related gene sets in Aβ-associated microenvironments.
(A) MAGMA associations of GWAS datasets for Alzheimer’s disease (AD, Jansen et al. 2019), frontotemporal dementia (FTD, Ferrari et al. 2014), and Parkinson’s disease (PD, Nalls et al. 2019) with Aβ-associated microenvironments profiled in human ITC. The results were presented in a heatmap, with the color scale indicating −log10 (p-value) and the numbers in the boxes indicating odd ratios for the enrichment. The p-value was thresholded at p = XXXX, allowing for the visualization of the most significant associations.
(B) Spatial gene set enrichment analysis with a bulk RNA-seq dataset of dorsolateral prefrontal cortex (DLPFC) collected from the ROSMAP cohort (Mstafavi et al. 2018). M109_Total refers to a gene module of 390 coexpressed genes strongly associated with cognitive decline and Aβ pathology in AD. M109_Top 112 is a subset of M109 containing top 112 interesting genes selected by an initial Baysian network, while M109_Valid 21 is a gene set containing 21 validated genes. These gene sets were compared and tested for their associations with Aβ-associated microenvironments profiled for enriched (top) and depleted (bottom) gene sets in the human ITC. The results were presented in a heatmap, with the color scale indicating −log10 (p-value) and the numbers in the boxes indicating odd ratios for the enrichment. The p-value was thresholded at p = XXXX, allowing for the visualization of the most significant associations.
(C) Spatial gene set enrichment analysis with a scRNA-seq dataset for AD (Grubman et al. 2019). Grubman et. al. identified AD-associated DEGs between case and control across 6 different cell types in the human entorhinal cortex, which were found to overlap with those identified in human DLPFC (Mathys et al. 2019). These cell type-specific gene sets were compared and tested for their associations with the Aβ-associated microenvironment in the human ITC, separated by enriched (top) and depleted (bottom) gene sets. The results are presented in a heatmap, with the color scale indicating −log10 (p-value) and the numbers in the boxes indicating odd ratios for the enrichment. The p-value was thresholded at p = XXXX, allowing for the visualization of the most significant associations.
[x] Confirm with Leo the description about TREM2 and PSEN2 regarding their enrichment profiles.
Figure S14. Spatial expression of Aβ-associated genes and AD risk genes.
.....TREM2 and PSEN2 had low tissue-wide gene expression and did not meet criteria for performing differential expression analysis (N/A). For brevity, Next was shortened to N. For spotplots, color scale indicates spot-level gene expression in log(counts).
shkwon17
commented
1 year ago
[x] Confirm with Leo logcounts vs log(counts) vs expression(logcounts)
Nat Neuro
PsychENCODE
currently on our Visium_SPG_AD
[x] Confirm with Leo the figure captions about the Harmony-based batch correction.
Figure S10. Harmony-based batch correction of Visium SRT data
(A) UMAP representation of Visium spots aggregated across 10 tissue sections illustrates the effects of donor and technical variability, colored by sample IDs. (B) Harmony was employed to minimize donor effects and technical variations across multiple Visium-SPG experiments.
[x] Confirm with Leo the figure captions about the volcano plots.
Fig.2 Identification of transcriptomic signatures in local microenvironments harboring AD-related neuropathology (D) Volcano plots depicting differentially expressed genes (DEGs) between Aβ pathology (Aβ) or adjacent Aβ pathology (Next_Aβ) versus rest of pathological categories. Each dot represents a DEG, plotted with its fold change (x-axis) and p-value (y-axis) for the magnitude and significance of the difference in gene expression. The dashed line represents a p-value threshold (<0.01), with DEGs below the line considered not significant (gray, Not sig.) Significant DEGs that passed the FDR threshold (>0.1) were labeled red and classified by their enrichment (>rest) and depletion (<rest) in gene expression according to the ‘enrichment’ model.
Figure S12. Inspecting biological functions and pathways of AD-associated microenvironments A) Volcano plots depicting DEGs in 5 other AD-related pathological categories based on the enrichment model. Each dot represents a DEG, plotted with its fold change (x-axis) and p-value (y-axis) for the magnitude and significance of the difference in gene expression, respectively. No DEGs (gray) passed the p-value and FDR threshold for these 5 pathological categories.
[ ] Confirm with Leo the figure captions about the GSEA results Figure S13. Enrichment of neurodegeneration- and dementia-related gene sets in Aβ-associated microenvironments.
(A) MAGMA associations of GWAS datasets for Alzheimer’s disease (AD, Jansen et al. 2019), frontotemporal dementia (FTD, Ferrari et al. 2014), and Parkinson’s disease (PD, Nalls et al. 2019) with Aβ-associated microenvironments profiled in human ITC. The results were presented in a heatmap, with the color scale indicating −log10 (p-value) and the numbers in the boxes indicating odd ratios for the enrichment. The p-value was thresholded at p = XXXX, allowing for the visualization of the most significant associations.
(B) Spatial gene set enrichment analysis with a bulk RNA-seq dataset of dorsolateral prefrontal cortex (DLPFC) collected from the ROSMAP cohort (Mstafavi et al. 2018). M109_Total refers to a gene module of 390 coexpressed genes strongly associated with cognitive decline and Aβ pathology in AD. M109_Top 112 is a subset of M109 containing top 112 interesting genes selected by an initial Baysian network, while M109_Valid 21 is a gene set containing 21 validated genes. These gene sets were compared and tested for their associations with Aβ-associated microenvironments profiled for enriched (top) and depleted (bottom) gene sets in the human ITC. The results were presented in a heatmap, with the color scale indicating −log10 (p-value) and the numbers in the boxes indicating odd ratios for the enrichment. The p-value was thresholded at p = XXXX, allowing for the visualization of the most significant associations.
(C) Spatial gene set enrichment analysis with a scRNA-seq dataset for AD (Grubman et al. 2019). Grubman et. al. identified AD-associated DEGs between case and control across 6 different cell types in the human entorhinal cortex, which were found to overlap with those identified in human DLPFC (Mathys et al. 2019). These cell type-specific gene sets were compared and tested for their associations with the Aβ-associated microenvironment in the human ITC, separated by enriched (top) and depleted (bottom) gene sets. The results are presented in a heatmap, with the color scale indicating −log10 (p-value) and the numbers in the boxes indicating odd ratios for the enrichment. The p-value was thresholded at p = XXXX, allowing for the visualization of the most significant associations.
[x] Confirm with Leo the description about TREM2 and PSEN2 regarding their enrichment profiles. Figure S14. Spatial expression of Aβ-associated genes and AD risk genes. .....TREM2 and PSEN2 had low tissue-wide gene expression and did not meet criteria for performing differential expression analysis (N/A). For brevity, Next was shortened to N. For spotplots, color scale indicates spot-level gene expression in log(counts).