This repository contains the scripts used for data curation, analyses and figure generation in our manuscript "Natural variations of cardiac performance in Drosophila identify a central function for Pdp1/dHLF in cardiac aging".

In this study, we analysed cardiac senescence in a natural population of flies using the Drosophila Genetic Reference Panel (DRPG). This permitted the discovery of an unprecedented number of variants and associated genes significantly associated to the natural variation of cardiac aging. We focused on the function of the PAR-domain bZIP transcription factor Pdp1 for which several variants were found associated with natural variation of the aging of multiple cardiac functional traits. We demonstrated that Pdp1 cell autonomously plays a central role in cardiac senescence and might do so by regulating mitochondria homeostasis.

A supplementary Zenodo repository contains all the scripts used for the GWAS in DGRP flies. Some of the scripts here used data from that repository and will be noted with an asterisk (*).

Repository content

• A_Input files/
  VEP analysis output of all the variants from DGRP.
• A_Raw_data/
  GWAS analysis output filtered with a pvalue of 0.001 threshold.
• B_Script_files/
  • DM6 variants annotation scripts/
    • cleanup_VEP_file.R
      Script used to curate the input VEP file to select only predicted consequences next to/in genes or in intergenic regions.
    • filter_pipeline_pval_maf_vep.R
      Script used to curate for each GWAS the predicted consequences on genes using a prioritisation method.
    • merge_gwas_vep_files.R
      Script merging information from VEP to the GWAS data before curation.
  • control_random_generation.R
    Script used to randomly select variants in the DGRP to create a control group.
  • table_gene-phenotype.R
    Matrix listing all Drosophila genes and the presence of a variant in the GWAS (3e-8 threshold).
• C_Output_files/
  Contains output from the scripts in B_Script_files/
• D_Figure_generation/
  • correlation localization variants/
    Script used to analyse variant localisation in GWAS compared to random control.
  • correlation spearman phenotypes/ (*)
    Analysis of correlation between phenotypes using Spearman test.
  • dgrpline_barplot/ (*)
    Representation of the difference between 1 week and 4 weeks phenotype for each DGRP line.
  • manhattan plot/ (*)
    Manhattan plot representation of all variants for each phenotype.
  • overlap_index/
    Analysis of the overlap of genes with significative variants between phenotypes.
  • population_boxplot/ (*)
    Analysis of the population difference at 1 week and 4 weeks for each phenotype.
  • reactionnorm_strains/ (*)
    Representation of the difference between 1 week and 4 weeks of each DGRP line for each phenotype.
  • FigT3-humanorthologs_hyper.R
    Analysis of the proportion of human orthologs identified in cardiac disorders and coronary artery diseases in the GWAS.