SCORPIUS

SCORPIUS an unsupervised approach for inferring linear developmental chronologies from single-cell RNA sequencing data. In comparison to similar approaches, it has three main advantages:

• It accurately reconstructs linear dynamic processes. The performance was evaluated using a quantitative evaluation pipeline and ten single-cell RNA sequencing datasets.

• It automatically identifies marker genes, speeding up knowledge discovery.

• It is fully unsupervised. Prior knowledge of the relevant marker genes or cellular states of individual cells is not required.

News:

• See news(package = "SCORPIUS") for a full list of changes to the package.

• A preprint is available on bioRxiv. Run citation("SCORPIUS") to obtain the corresponding citation information.

• Check out our review on Trajectory Inference methods!

Installing SCORPIUS

You can install:

• the latest released version from CRAN with

  install.packages("SCORPIUS")

• the latest development version from GitHub with

  devtools::install_github("rcannood/SCORPIUS", build_vignettes = TRUE)

If you encounter a bug, please file a minimal reproducible example on the issues page.

Learning SCORPIUS

To get started, read the introductory example below, or read one of the vignettes containing more elaborate examples:

• Investigating dendritic cell maturation in dendritic cell progenitors:
  vignette("ginhoux", package="SCORPIUS")
• Trajectory inference from simulated data:
  vignette("simulated-data", package="SCORPIUS")

Introductory example

This section describes the main workflow of SCORPIUS without going in depth in the R code. For a more detailed explanation, see the vignettes listed below.

To start using SCORPIUS, simply write:

library(SCORPIUS)

The ginhoux dataset (See Schlitzer et al. 2015) contains 248 dendritic cell progenitors in one of three cellular cellular states: MDP, CDP or PreDC. Note that this is a reduced version of the dataset, for packaging reasons. See ?ginhoux for more info.

data(ginhoux)
expression <- ginhoux$expression
group_name <- ginhoux$sample_info$group_name

With the following code, SCORPIUS reduces the dimensionality of the dataset and provides a visual overview of the dataset. In this plot, cells that are similar in terms of expression values will be placed closer together than cells with dissimilar expression values.

space <- reduce_dimensionality(expression, "spearman")
draw_trajectory_plot(space, group_name, contour = TRUE)

To infer and visualise a trajectory through these cells, run:

traj <- infer_trajectory(space)
draw_trajectory_plot(space, group_name, traj$path, contour = TRUE)

To identify candidate marker genes, run:

# warning: setting num_permutations to 10 requires a long time (~30min) to run!
# set it to 0 and define a manual cutoff for the genes (e.g. top 200) for a much shorter execution time.
gimp <- gene_importances(
  expression, 
  traj$time, 
  num_permutations = 10, 
  num_threads = 8, 
  ntree = 10000,
  ntree_perm = 1000
) 

To select the most important genes and scale its expression, run:

gimp$qvalue <- p.adjust(gimp$pvalue, "BH", length(gimp$pvalue))
gene_sel <- gimp$gene[gimp$qvalue < .05]
expr_sel <- scale_quantile(expression[,gene_sel])

To visualise the expression of the selected genes, use the draw_trajectory_heatmap function.

draw_trajectory_heatmap(expr_sel, traj$time, group_name)

Finally, these genes can also be grouped into modules as follows:

modules <- extract_modules(scale_quantile(expr_sel), traj$time, verbose = F)
draw_trajectory_heatmap(expr_sel, traj$time, group_name, modules)

Latest changes

Check out news(package = "SCORPIUS") for a full list of changes.

Recent changes in SCORPIUS 1.0.4

Minor changes

• Added extra customisation parameters to draw_trajectory_plot() and draw_trajectory_heatmap().

Optimisation

• Fixed internal function check_numeric_matrix() such that it does not run for ages when applied to a large sparse matrix.

• Minor improvement in infer_initial_trajectory() when calculating the distance from points to along candidate segments.

Recent changes in SCORPIUS 1.0.3 (27-05-2019)

Optimisation

• infer_trajectory(): Use princurve’s approx_points parameter, which greatly speeds up for trajectory inference for large number of samples.

Major changes

• Use dynutils’ calculate_distance() instead of correlation_distance() and euclidean_distance().

Documentation

• Vignettes were updated.

• Added cran-comments.md.

• Added recent news (inst/NEWS.md).

• Added citation information (inst/CITATION).

• Added support for sparsity in extract_modules() and dimensionality_reduction().

Minor changes

• Use scaling functions from dynutils (scale_minmax(), scale_quantile(), scale_uniform()).

• Expanded unit tests.

• Renormalise the original ginhoux data using dynnormaliser and rerun all vignettes.

• Moved cmdscale_withlandmarks() to dyndimred.

Bug fixes

• extract_modules(): smooth.spline() now requires at least 4 unique values.

Deprecation

• Deprecated unused functions evaluate_trajectory() and evaluate_dim_red(). Use dyneval::evaluate_ti_method() instead.

References

Schlitzer, Andreas, V Sivakamasundari, Jinmiao Chen, Hermi Rizal Bin Sumatoh, Jaring Schreuder, Josephine Lum, Benoit Malleret, et al. 2015. “Identification of cDC1- and cDC2-committed DC progenitors reveals early lineage priming at the common DC progenitor stage in the bone marrow.” Nature Immunology 16 (7): 718–26. https://doi.org/10.1038/ni.3200.