Skip to content

Malignant meta-programs#

Motivation#

Meta-program analyses are powerful strategies for uncovering intratumor heterogeneity (ITH). We built our meta-program module based on data published by Gavish et al. These meta-programs encompass a range of cellular processes, covering both generic patterns (such as cell cycle and stress) and cancer lineage-specific ones, e.g., 11 ITH hallmarks.

Step-by-Step#

1. Running pipeline#

1.1. On the HPC#

HPC

  • workflow_level = Malignant
  • input_meta_programs_db = ./assets/meta_programs_database.csv
  • input_cell_category = Malignant
  • input_heatmap_annotation = source_name;seurat_clusters
nextflow run main.nf --workflow_level Malignant --project_name Training --sample_csv sample_table.csv --meta_data meta_data.csv --cancer_type Ovarian -resume -profile seadragon

1.2. On Cirro#

Alternatively, we execute this task on Cirro.

Cirro

  • Defining the pipeline entrypoints = Malignant
  • Input meta-program = Default
  • Meta-program cell category = Malignant
  • Meta-data columns to be displayed on heatmap = source_name;seurat_clusters

On Cirro, users should (Do not run):

  • Navigate to the Pipelines tab and enter "BTC scRNA Pipeline" in the search engine.
  • Change the Dataset to BTC Training dataset and the Copy Parameters From option to Run_01.
  • Double-check the aforementioned parameters and click Run.

2. Inspecting report#

For convenience the figures can be located in the Test_Malignant_meta_report.html report within the Run_02 dataset.

Info

The database for meta-programs is stored in the pipeline repository. You can access it here.

2.1. Meta-program and ITH prediction#

The heatmap offers a detailed overview of meta-programs associated with malignant cells. Moreover, users have the option to include annotations related to meta-data, such as source_name and seurat_clusters.

Image caption

2.2. ITH signatures#

Similar to the cell annotation module, we also offer a FeaturePlot panel that reports the Module score for each ITH meta-program across malignant cells.

Image caption

3. Exercise: Customizing the meta-program annotation#

Question

Considering meta-data for this dataset, is it possible to add or remove annotations on the heatmap? A: Run_Meta

Please note: When configuring the pipeline on Cirro, ensure that the Dataset is set to BTC Training dataset and select Run_02 for the Copy Parameters From option. Additionally, configure the Entrypoint parameter to Malignant.

Tip: Accelerate the process by skipping DEG analysis

Reference#

  1. Hallmarks of transcriptional intratumour heterogeneity across a thousand tumours