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SCmultiomics Analysis in PASC

18 Cross-modal Integration

18.1 WNN graph construction 


combined <- FindMultiModalNeighbors(combined ,
                                  reduction.list = list("rna.integration", "umap.atac"),
                                  dims.list = list(1:ncol(Embeddings(combined,"rna.integration")),
                                                   1:ncol(Embeddings(combined,"rna.integration"))),
                                  modality.weight.name = c("RNA.weight","ATAC.weight"),
                                  verbose = TRUE)


combined <- RunUMAP(combined,
                    nn.name        = "weighted.nn",
                    assay          = "RNA",
                    reduction.name = "integration.wnn",
                    reduction.key  = "WNN_")

resolution <- 2
combined   <- FindClusters(combined,
                           graph.name = "wsnn",
                           resolution = seq(0.1, resolution, 0.1))

18.2 WNN UMAP 

DimPlot(combined, reduction = 'integration.wnn', group.by = "sample")
DimPlot(combined, reduction = 'integration.wnn', group.by = "sample_donor")
DimPlot(combined, reduction = 'integration.wnn', group.by = "individual_condition")
DimPlot(combined, reduction = 'integration.wnn', group.by = "SingleR.labels")

18.3 WNN UMAP — cell types split by condition 

DimPlot(combined,
        reduction = 'integration.wnn',
        group.by  = "SingleR.labels",
        split.by  = "individual_condition")

18.4 Modality weights

The RNA and ATAC weights per cell reflect how much each modality contributes to defining each cell’s neighbourhood. Cells where one modality dominates (weight close to 1) may have poor quality in the other modality.

VlnPlot(combined, features = "RNA.weight",  group.by = "SingleR.labels", pt.size = 0) + NoLegend()
VlnPlot(combined, features = "ATAC.weight", group.by = "SingleR.labels", pt.size = 0) + NoLegend()

18.5 Clustree — WNN resolution sweep 

clustree(combined, prefix = 'wsnn_res.', show_axis = TRUE) +
  theme(legend.key.size = unit(0.20, 'cm'))
SaveSeuratRds(combined, "data/seurat_object_cross_modal_integration.rds")