Clustering and metaclustering

library(tidytof)
library(dplyr)

Often, clustering single-cell data to identify communities of cells with shared characteristics is a major goal of high-dimensional cytometry data analysis.

To do this, {tidytof} provides the tof_cluster() verb. Several clustering methods are implemented in {tidytof}, including the following:

Each of these methods are wrapped by tof_cluster().

Clustering with tof_cluster()

To demonstrate, we can apply the PhenoGraph clustering algorithm to {tidytof}’s built-in phenograph_data. Note that phenograph_data contains 3000 total cells (1000 each from 3 clusters identified in the original PhenoGraph publication). For demonstration purposes, we also metacluster our PhenoGraph clusters using k-means clustering.

data(phenograph_data)

set.seed(203L)

phenograph_clusters <-
    phenograph_data |>
    tof_preprocess() |>
    tof_cluster(
        cluster_cols = starts_with("cd"),
        num_neighbors = 50L,
        distance_function = "cosine",
        method = "phenograph"
    ) |>
    tof_metacluster(
        cluster_col = .phenograph_cluster,
        metacluster_cols = starts_with("cd"),
        num_metaclusters = 3L,
        method = "kmeans"
    )

phenograph_clusters |>
    dplyr::select(sample_name, .phenograph_cluster, .kmeans_metacluster) |>
    head()
#> # A tibble: 6 × 3
#>   sample_name            .phenograph_cluster .kmeans_metacluster
#>   <chr>                  <chr>               <chr>              
#> 1 H1_PhenoGraph_cluster1 5                   2                  
#> 2 H1_PhenoGraph_cluster1 1                   2                  
#> 3 H1_PhenoGraph_cluster1 5                   2                  
#> 4 H1_PhenoGraph_cluster1 1                   2                  
#> 5 H1_PhenoGraph_cluster1 1                   2                  
#> 6 H1_PhenoGraph_cluster1 5                   2

The outputs of both tof_cluster() and tof_metacluster() are a tof_tbl identical to the input tibble, but now with the addition of an additional column (in this case, “.phenograph_cluster” and “.kmeans_metacluster”) that encodes the cluster id for each cell in the input tof_tbl. Note that all output columns added to a tibble or tof_tbl by {tidytof} begin with a full-stop (“.”) to reduce the likelihood of collisions with existing column names.

Because the output of tof_cluster is a tof_tbl, we can use dplyr’s count method to assess the accuracy of our clustering procedure compared to the original clustering from the PhenoGraph paper.

phenograph_clusters |>
    dplyr::count(phenograph_cluster, .kmeans_metacluster, sort = TRUE)
#> # A tibble: 4 × 3
#>   phenograph_cluster .kmeans_metacluster     n
#>   <chr>              <chr>               <int>
#> 1 cluster2           1                    1000
#> 2 cluster3           3                    1000
#> 3 cluster1           2                     995
#> 4 cluster1           3                       5

Here, we can see that our clustering procedure groups most cells from the same PhenoGraph cluster with one another (with a small number of mistakes).

To change which clustering algorithm tof_cluster uses, alter the method flag.

# use the kmeans algorithm
phenograph_data |>
    tof_preprocess() |>
    tof_cluster(
        cluster_cols = contains("cd"),
        method = "kmeans"
    )

# use the flowsom algorithm
phenograph_data |>
    tof_preprocess() |>
    tof_cluster(
        cluster_cols = contains("cd"),
        method = "flowsom"
    )

To change the columns used to compute the clusters, change the cluster_cols flag. And finally, if you want to return a one-column tibble that only includes the cluster labels (as opposed to the cluster labels added as a new column to the input tof_tbl), set augment to FALSE.

# will result in a tibble with only 1 column (the cluster labels)
phenograph_data |>
    tof_preprocess() |>
    tof_cluster(
        cluster_cols = contains("cd"),
        method = "kmeans",
        augment = FALSE
    ) |>
    head()
#> # A tibble: 6 × 1
#>   .kmeans_cluster
#>   <chr>          
#> 1 9              
#> 2 9              
#> 3 2              
#> 4 19             
#> 5 12             
#> 6 19

Session info

sessionInfo()
#> R version 4.6.0 (2026-04-24)
#> Platform: x86_64-pc-linux-gnu
#> Running under: Ubuntu 24.04.4 LTS
#> 
#> Matrix products: default
#> BLAS:   /usr/lib/x86_64-linux-gnu/openblas-pthread/libblas.so.3 
#> LAPACK: /usr/lib/x86_64-linux-gnu/openblas-pthread/libopenblasp-r0.3.26.so;  LAPACK version 3.12.0
#> 
#> locale:
#>  [1] LC_CTYPE=en_US.UTF-8       LC_NUMERIC=C              
#>  [3] LC_TIME=en_US.UTF-8        LC_COLLATE=en_US.UTF-8    
#>  [5] LC_MONETARY=en_US.UTF-8    LC_MESSAGES=en_US.UTF-8   
#>  [7] LC_PAPER=en_US.UTF-8       LC_NAME=C                 
#>  [9] LC_ADDRESS=C               LC_TELEPHONE=C            
#> [11] LC_MEASUREMENT=en_US.UTF-8 LC_IDENTIFICATION=C       
#> 
#> time zone: Etc/UTC
#> tzcode source: system (glibc)
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#> attached base packages:
#> [1] stats4    stats     graphics  grDevices utils     datasets  methods  
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#>  [1] HDCytoData_1.32.0           flowCore_2.24.0            
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#> [19] dplyr_1.2.1                 tidytof_1.6.0              
#> [21] rmarkdown_2.31             
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