experiments

Subset of code and data to reproduce main results of the paper

Download the main data scDRS_data_release_092121 (3.6 GB) and scDRS score files for TMS FACS + 74 diseases/traits scDRS_data_release_092121.score_file_tmsfacs (36.3 GB).

Codes are at ./job.reproduce

Compute scDRS scores for TMS FACS + 74 diseases/traits

• Score files were already included in scDRS_data_release_092121.score_file_tmsfacs.
• You can also compute them yourself by the bash sript reproduce_compute_score.tms_facs_with_cov.magma_10kb_1000.sh
• Set DATA_PATH to your local folder of scDRS_data_release_092121 (containing TMS FACS data and .gs files) and run the script.

Cell type-level analysis (Fig. 3):

• You can reproduce the results using reproduce_celltype.ipynb
• Set DATA_PATH to your local folder of scDRS_data_release_092121 and run the notebook.

T cell analysis (Fig. 4A-C):

• You can reproduce the results using reproduce_tcell.ipynb
• Set DATA_PATH to your local folder of scDRS_data_release_092121, set SCORE_FILE_PATH to your local folder of scDRS_data_release_092121.score_file_tmsfacs and run the notebook.

T cell gene prioritization (Fig. 4D):

• You can reproduce the results using reproduce_tcell_gene.ipynb
• Set DATA_PATH to your local folder of scDRS_data_release_092121, set SCORE_FILE_PATH to your local folder of scDRS_data_release_092121.score_file_tmsfacs and run the notebook.

Neuron analysis (Fig. 5A,B):

• You can reproduce the results using reproduce_neuron.ipynb
• Set DATA_PATH to your local folder of scDRS_data_release_092121 and run the notebook.

Hepatocyte analysis (Fig. 5C,D):

• You can reproduce the results using reproduce_neuron.ipynb
• Set DATA_PATH to your local folder of scDRS_data_release_092121, set SCORE_FILE_PATH to your local folder of scDRS_data_release_092121.score_file_tmsfacs and run the notebook.

Complete code

Data curation: job.curate_data

Curate information for 74 diseases/traits:

• Curate information for the 74 diseases: job.curate_data/get_trait_list.ipynb

Curate gene set (.gs) files:

• .gs file for 74 diseases: job.curate_data/curate_gs_file.ipynb
• .gs file for T cell signatures: job.curate_data/curate_gs.tcell_signature.ipynb
• .gs file for ploidy signatures: job.curate_data/curate_ploidy_gs.ipynb
• .gs file for zonation signatures: job.curate_data/curate_zonation_gs.ipynb
• .gs file for metabolic pathways: job.curate_data/curate_gs.metabolic.ipynb

Curate scRNA-seq data sets:

• TS FACS: job.curate_data/curate_ts_data.ipynb
• Cano-Gamez & Soskic et al.: job.curate_data/curate_canogamez_tcell_data.ipynb
• Nathan et al.: job.curate_data/curate_nathan_tcell_data.ipynb
• Aizarani et al.: job.curate_data/curate_aizarani_liver_atlas_data.ipynb
• Halpern & Shenhav et al.: job.curate_data/curate_halpern_mouse_liver_data.ipynb
• Richter & Deligiannis et al.: job.curate_data/curate_richter_hepatocyte_data.ipynb

Compute scDRS scores: job.compute_score

• TMS FACS + 74 diseases: job.compute_score/compute_score.tms_facs_with_cov.magma_10kb_1000.sh
• TMS FACS + T cell signatures: job.compute_score/compute_score.tms_facs_with_cov.tcell_sig.sh
• TMS FACS + metabolic: job.compute_score/compute_score.tms_facs_with_cov.hep_metabolic.sh
• TMS droplet + 74 diseases: job.compute_score/compute_score.tms_droplet_with_cov.magma_10kb_1000.sh
• TS FACS + 74 diseases: job.compute_score/compute_score.ts_facs_with_cov.magma_10kb_1000.sh

Scehma (Fig. 1): job.schema

Make schematic figures.

Simulation (Fig. 2): job.simulation

Data generation:

• Generate the TMS FACS 10K subsampled data and null gene sets: job.simulation/generate_null_simulation_data.ipynb
• Generate causal gene sets and perturbation configurations: job.simulation/generate_causal_simulation_data.ipynb

Compute results:

• Compute scDRS scores for null simulations: job.simulation/compute_simu_score.sh
• Compute Seurat scores for null simulations: job.simulation/compute_simu_score_scanpy.sh
• Compute Vision scores for null simulations: job.simulation/compute_simu_score_vision.sh
• Compute VAM scores for null simulations: job.simulation/call_R_vam.sh
• Compute scores (scDRS/Seurat/Vision) for causal simulations (500 random causal cells): job.simulation/compute_perturb_simu_score.sh
• Compute scores (scDRS/Seurat/Vision) for causal simulations (B cells causal): job.simulation/compute_perturb_simu_score_Bcell.sh

Make figures:

• Make figures for null simulations: job.simulation/make_figure.null_simulation.ipynb
• Make figures for causal simulations (500 random causal cells): job.simulation/make_figure.causal_simulation.ipynb
• Make figures for causal simulations (B cells causal): job.simulation/make_figure.causal_simulation_Bcell.ipynb

Cell type-level results (Fig. 3): job.celltype_association

• Summary of the cell-type association results: job.celltype_association/summary_ct.ipynb
• Main analysis: job.celltype_association/main_figure.ipynb
• Comparison of cell-type association for three atlas datasets: TMS FACS, TMS droplet, TS FACS: job.celltype_association/atlas_compare.ipynb
• Relationship between scDRS power and heritability, polygenicity: job.celltype_association/optim_param.ipynb
• Comparison of cell-type association to LDSC-SEG: job.celltype_association/ldsc_compare.ipynb
• Effects of gene sets for scDRS power: job.celltype_association/vary_geneset.ipynb

T cell example (Fig. 4): job.case_tcell

• Reprocess TMS T cells and assign effectorness gradients: job.case_tcell/s1_reprocess_tms_tcell.ipynb
• Main analysis: job.case_tcell/s3_analysis_tcell.ipynb
• Replication in Cano-Gamez & Soskic et al. and Nathan et al. data: job.case_tcell/s4_analysis_tcell.replication.ipynb
• Cluster-level LDSC-SEG analysis: job.case_tcell/s5_compare_ldsc_cluster_4res.ipynb
• Disease gene prioritization: job.case_tcell/s6_gene_prioritization.ipynb

Neuron example (Fig. 5AB): job.ca1_pyramidal

• Main analysis (Fig. 5AB): job.ca1_pyramidal/main_figure.ipynb
• Analysis of neurons in TMS FACS dataset: job.ca1_pyramidal/tms.ipynb
• Analysis of Zeisel et al. 2015 dataset: job.ca1_pyramidal/zeisel.ipynb
• Verification of the inferred spatial coordinates: job.ca1_pyramidal/spatial_verify.ipynb

Hepatocyte example (Fig. 5CD): job.case_hepatocyte

• Reprocess TMS hepatocytes: job.case_hepatocyte/s1_reprocess_tms_hep.ipynb
• Main analysis: job.case_hepatocyte/s3_analysis_hep.ipynb