A method for investigating transmission distortion among human sperm

This repository contains the analyses performed for the study "A method for low-coverage single-gamete sequence analysis demonstrates adherence to Mendel’s first law across a large sample of human sperm". This paper is published in eLife.

Results

Evaluating performance on simulated data

Data generation

For each different combination of study design:

• analysis_scripts/sim-scripts/generative_model_for_rhapsodi.R run by analysis_scripts/sim-scripts/run_genModel.sh or analysis_scripts/sim-scripts/run_genModel_3args.sh

Followed by one of the following:

• analysis_scripts/sim-scripts/assess_with_rhapsodi.R run by analysis_scripts/sim-scripts/run_assess_with_rhapsodi.sh or analysis_scripts/sim-scripts/run_assess_with_rhapsodi_2args.sh
• analysis_scripts/sim-scripts/assess_with_rhapsodi_thread_arg.R run by analysis_scripts/sim-scripts/run_assess_with_rhapsodi_thread_arg.sh
• analysis_scripts/sim-scripts/assess_with_rhapsodi_mparams.R run by analysis_scripts/sim-scripts/run_assess_with_rhapsodi_mparams.sh

Statstics reported in text

• analysis_scripts/get_sim_stats.R

Plotting

Fig 2

• plotting/plot_rhapsodi_main_gen_fig.R
  • Rdata files for streamlined plotting in plotting/main_heatmap_rdata

Fig 2 Supplemental Fig 2

• plotting/plot_rhapsodi_supp_gen_fig.R
  • Rdata files for streamlined plotting in plotting/supp_heatmap_rdata

Fig 2 Supplemental Fig 3

Make Rdata files

• analysis_scripts/sim-scripts/save_true_nsnp_vals.R
  • Rdata file in rhapsodi_scripts/test_data_rhapsodi_gen
• plotting/supp_recomb/plot_supfig3_recombination_info.R
  • Rdata files plotting/supfig3_rdata

Plot

• plotting/supp_recomb/plot_bp_res.R and plotting/supp_recomb/plot_supfig3_recomb_fn_fp.R
  • Rdata files for streamlined plotting in plotting/supp_recomb

Fig 2 Supplemental Fig 4-7

• plotting/robustness/plot_rhapsodi_robust_fig.R
  • Rdata files for streamlined plotting in plotting/robustness

Benchmarking against existing methods: Hapi and HapCUT2

Data generation

• Same from data generation in "Evaluating performance on simulated data"
• analysis_scripts/hapi_benchmarking.R

Plotting

Fig 3, 3S1, 3S2

• plotting/rhapsodi_hapi_benchmarking_plot_scripts.R

Application to data from human sperm

Data generation

• analysis_scripts/sperm-data/subset_data.R run by analysis_scripts/sperm-data/subset_bash.sh
• analysis_scripts/sperm-data/filter_rhapsodi_TDscan.R run by analysis_scripts/sperm-data/slurm_filter_rhapsodi_TDscan.sh and analysis_scripts/sperm-data/submit_slurm_filter_rhapsodi_TDscan.sh

Statistics reported in text

• analysis_scripts/get_stats.R

Statistical power to detect moderate and strong TD

Plotting

Fig 4, 4S1

• plotting/power_analyses/power_analysis_sperm.R

Fig 4S2, 4S3

• plotting/TD_sim_plotting.R

Fig 4S4

• plotting/power_analyses/informative_transmissions_TDT.R

Strict adherence to Mendelian expectations across sperm genomes

Data generation

• Same from data generation in "Application to data from human sperm"

Plotting

Fig 5

• plotting/manhattan_all_donors_11052021.R

Fig 5S2

Fig 5S3

• plotting/identify_segmental_dups.R

Fig 5S4, 5S5

• plotting/plot_recombination_map.R
• Rdata files for streamlined plotting in plotting/supp_recomb

No global signal of biased transmission in human sperm

Data generation

• analysis_scripts/run_plink/make_ped_file.R run by analysis_scripts/run_plink/submit_slurm_make_ped.sh calling analysis_scripts/run_plink/slurm_make_ped.sh and analysis_scripts/run_plink/slurm_inf_make_ped.sh

• analysis_scripts/get_snps_prune.R
• analysis_scripts/sim-scripts/null_sim.R run by sim-scripts/sim_wrapper.sh

Plotting

Fig 6

• Panel A: plotting/qqplot.R
• Panel B: plotting/plot_global_sims.R