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This function calculates gene-set scores from the specified database (db) for each lineage using the specified scoring method (score_method). It then treats these scores as expression values and uses them as input to the RunDynamicFeatures function to identify dynamically enriched terms along the lineage.

Usage

RunDynamicEnrichment(
  srt,
  lineages,
  score_method = "AUCell",
  layer = "data",
  assay = NULL,
  min_expcells = 20,
  r.sq = 0.2,
  dev.expl = 0.2,
  padjust = 0.05,
  IDtype = "symbol",
  species = "Homo_sapiens",
  db = "GO_BP",
  db_update = FALSE,
  db_version = "latest",
  convert_species = TRUE,
  Ensembl_version = NULL,
  mirror = NULL,
  TERM2GENE = NULL,
  TERM2NAME = NULL,
  minGSSize = 10,
  maxGSSize = 500,
  cores = 1,
  verbose = TRUE,
  seed = 11
)

Arguments

srt

A Seurat object containing the results of differential expression analysis (RunDEtest). If specified, the genes and groups will be extracted from the Seurat object automatically. If not specified, the geneID and geneID_groups arguments must be provided.

lineages

A character vector specifying the lineages to plot.

score_method

The method to use for scoring. Can be "Seurat", "AUCell", or "UCell". Default is "Seurat".

layer

A character vector specifying the layer in the Seurat object to use. Default is "counts".

assay

A character vector specifying the assay in the Seurat object to use. Default is NULL.

min_expcells

The minimum number of expected cells. Default is 20.

r.sq

The R-squared threshold. Default is 0.2.

dev.expl

The deviance explained threshold. Default is 0.2.

padjust

The p-value adjustment threshold. Default is 0.05.

IDtype

A character vector specifying the type of gene IDs in the srt object or geneID argument. This argument is used to convert the gene IDs to a different type if IDtype is different from result_IDtype.

species

A character vector specifying the species for which the analysis is performed.

db

A character vector specifying the name of the database to be used for enrichment analysis.

db_update

Whether the gene annotation databases should be forcefully updated. If set to FALSE, the function will attempt to load the cached databases instead. Default is FALSE.

db_version

A character vector specifying the version of the database to be used. This argument is ignored if db_update is TRUE. Default is "latest".

convert_species

Whether to use a species-converted database when the annotation is missing for the specified species. Default is TRUE.

Ensembl_version

Ensembl database version. If NULL, use the current release version.

mirror

Specify an Ensembl mirror to connect to. The valid options here are "www", "uswest", "useast", "asia".

TERM2GENE

A data frame specifying the gene-term mapping for a custom database. The first column should contain the term IDs, and the second column should contain the gene IDs.

TERM2NAME

A data frame specifying the term-name mapping for a custom database. The first column should contain the term IDs, and the second column should contain the corresponding term names.

minGSSize

The minimum size of a gene set to be considered in the enrichment analysis.

maxGSSize

The maximum size of a gene set to be considered in the enrichment analysis.

cores

The number of cores to use for parallelization with foreach::foreach. Default is 1.

verbose

Whether to print the message. Default is TRUE.

seed

An integer specifying the random seed. Default is 11.

Examples

data(pancreas_sub)
pancreas_sub <- standard_scop(pancreas_sub)
#> StandardPC_ 1 
#> Positive:  Aplp1, Cpe, Gnas, Fam183b, Map1b, Hmgn3, Pcsk1n, Chga, Tuba1a, Bex2 
#> 	   Syt13, Isl1, 1700086L19Rik, Pax6, Chgb, Scgn, Rbp4, Scg3, Gch1, Camk2n1 
#> 	   Cryba2, Pcsk2, Pyy, Tspan7, Mafb, Hist3h2ba, Dbpht2, Abcc8, Rap1b, Slc38a5 
#> Negative:  Spp1, Anxa2, Sparc, Dbi, 1700011H14Rik, Wfdc2, Gsta3, Adamts1, Clu, Mgst1 
#> 	   Bicc1, Ldha, Vim, Cldn3, Cyr61, Rps2, Mt1, Ptn, Phgdh, Nudt19 
#> 	   Smtnl2, Smco4, Habp2, Mt2, Col18a1, Rpl12, Galk1, Cldn10, Acot1, Ccnd1 
#> StandardPC_ 2 
#> Positive:  Rbp4, Tagln2, Tuba1b, Fkbp2, Pyy, Pcsk2, Iapp, Tmem27, Meis2, Tubb4b 
#> 	   Pcsk1n, Dbpht2, Rap1b, Dynll1, Tubb2a, Sdf2l1, Scgn, 1700086L19Rik, Scg2, Abcc8 
#> 	   Atp1b1, Hspa5, Fam183b, Papss2, Slc38a5, Scg3, Mageh1, Tspan7, Ppp1r1a, Ociad2 
#> Negative:  Neurog3, Btbd17, Gadd45a, Ppp1r14a, Neurod2, Sox4, Smarcd2, Mdk, Pax4, Btg2 
#> 	   Sult2b1, Hes6, Grasp, Igfbpl1, Gpx2, Cbfa2t3, Foxa3, Shf, Mfng, Tmsb4x 
#> 	   Amotl2, Gdpd1, Cdc14b, Epb42, Rcor2, Cotl1, Upk3bl, Rbfox3, Cldn6, Cer1 
#> StandardPC_ 3 
#> Positive:  Nusap1, Top2a, Birc5, Aurkb, Cdca8, Pbk, Mki67, Tpx2, Plk1, Ccnb1 
#> 	   2810417H13Rik, Incenp, Cenpf, Ccna2, Prc1, Racgap1, Cdk1, Aurka, Cdca3, Hmmr 
#> 	   Spc24, Kif23, Sgol1, Cenpe, Cdc20, Hist1h1b, Cdca2, Mxd3, Kif22, Ska1 
#> Negative:  Anxa5, Pdzk1ip1, Acot1, Tpm1, Anxa2, Dcdc2a, Capg, Sparc, Ttr, Pamr1 
#> 	   Clu, Cxcl12, Ndrg2, Hnf1aos1, Gas6, Gsta3, Krt18, Ces1d, Atp1b1, Muc1 
#> 	   Hhex, Acadm, Spp1, Enpp2, Bcl2l14, Sat1, Smtnl2, 1700011H14Rik, Tgm2, Fam159a 
#> StandardPC_ 4 
#> Positive:  Glud1, Tm4sf4, Akr1c19, Cldn4, Runx1t1, Fev, Pou3f4, Gm43861, Pgrmc1, Arx 
#> 	   Cd200, Lrpprc, Hmgn3, Ppp1r14c, Pam, Etv1, Tsc22d1, Slc25a5, Akap17b, Pgf 
#> 	   Fam43a, Emb, Jun, Krt8, Dnajc12, Mid1ip1, Ids, Rgs17, Uchl1, Alcam 
#> Negative:  Ins2, Ins1, Ppp1r1a, Nnat, Calr, Sytl4, Sdf2l1, Iapp, Pdia6, Mapt 
#> 	   G6pc2, C2cd4b, Npy, Gng12, P2ry1, Ero1lb, Adra2a, Papss2, Arhgap36, Fam151a 
#> 	   Dlk1, Creld2, Gip, Tmem215, Gm27033, Cntfr, Prss53, C2cd4a, Lyve1, Ociad2 
#> StandardPC_ 5 
#> Positive:  Pdx1, Nkx6-1, Npepl1, Cldn4, Cryba2, Fev, Jun, Chgb, Gng12, Adra2a 
#> 	   Mnx1, Sytl4, Pdk3, Gm27033, Nnat, Chga, Ins2, 1110012L19Rik, Enho, Krt7 
#> 	   Mlxipl, Tmsb10, Flrt1, Pax4, Tubb3, Prrg2, Gars, Frzb, BC023829, Gm2694 
#> Negative:  Irx2, Irx1, Gcg, Ctxn2, Tmem27, Ctsz, Tmsb15l, Nap1l5, Pou6f2, Gria2 
#> 	   Ghrl, Peg10, Smarca1, Arx, Lrpap1, Rgs4, Ttr, Gast, Tmsb15b2, Serpina1b 
#> 	   Slc16a10, Wnk3, Ly6e, Auts2, Sct, Arg1, Dusp10, Sphkap, Dock11, Edn3 
pancreas_sub <- RunSlingshot(
  pancreas_sub,
  group.by = "SubCellType",
  reduction = "UMAP"
)
#> Error in loadNamespace(x): there is no package called ‘slingshot’
pancreas_sub <- RunDynamicFeatures(
  pancreas_sub,
  lineages = "Lineage1",
  n_candidates = 200
)
#> Error in subset(srt, cell = rownames(srt@meta.data)[is.finite(srt@meta.data[[l]])]): No cells found
ht1 <- DynamicHeatmap(
  pancreas_sub,
  lineages = "Lineage1",
  cell_annotation = "SubCellType",
  n_split = 4
)
#> Error in DynamicHeatmap(pancreas_sub, lineages = "Lineage1", cell_annotation = "SubCellType",     n_split = 4): Lineages: Lineage1 is not in the meta data of the Seurat object
ht1$plot
#> Error: object 'ht1' not found

pancreas_sub <- RunDynamicEnrichment(
  pancreas_sub,
  lineages = "Lineage1",
  score_method = "UCell",
  db = "GO_BP",
  species = "Mus_musculus"
)
#> Error in RunDynamicEnrichment(pancreas_sub, lineages = "Lineage1", score_method = "UCell",     db = "GO_BP", species = "Mus_musculus"): "Lineage1" info not found in the srt object. Should perform
#> `RunDynamicFeatures()` first
ht2 <- DynamicHeatmap(
  pancreas_sub,
  assay = "GO_BP",
  lineages = "Lineage1_GO_BP",
  cell_annotation = "SubCellType",
  n_split = 4,
  split_method = "kmeans-peaktime"
)
#> Error in DynamicHeatmap(pancreas_sub, assay = "GO_BP", lineages = "Lineage1_GO_BP",     cell_annotation = "SubCellType", n_split = 4, split_method = "kmeans-peaktime"): Lineages: Lineage1_GO_BP is not in the meta data of the Seurat object
ht2$plot
#> Error: object 'ht2' not found