Supplementary package (version 5, 28 October 2026)
Article: "Evolutionary Architecture of Longevity Regulators: Directional Conservation and Divergence from Yeast to Human Cells"
Journal: Biogerontology
Author: Davis W. Cheng, Rocky Institute of Biotechnology, Clovis, California, USA (dcheng@rockybiotech.org)

Contents
  Supplementary_Tables_S1-S10_v4.xlsx   Supplementary Tables S1-S10 (README sheet describes each)
  figures/                          Figures 1-6 (PNG, 300 dpi; PDF vector)
  outputs/                          Intermediate tables produced by the scripts
  code/                             Analysis scripts

Run order (Python 3; pandas, numpy, scipy, statsmodels, networkx, scikit-learn, matplotlib, requests, openpyxl, pillow).
Run each script from inside code/; data go to ../data, results to ../outputs and ../figures.
  00_download_data.sh      download public sources; keep human protein-coding ortholog targets only
  12_catalogue.py          controlled single-gene effects (SGD, GenAge Build 21, CellAge Build 3) -> human orthologs
                           (Alliance 9.0.0, stringent; GenAge genes matched by Entrez ID -> FB/WB/MGI ID, not by symbol)
  13_core.py               pairwise convergence, direction concordance, permutation test (seed 20261019), core genes
  13b_string.py            STRING v12.5 network (score >= 0.7, exact-symbol mapping), Louvain modules (seed 1)
  13c_gost.py              g:Profiler enrichment vs genome and vs all 3,399 aging genes
  13d_module_stability.py  module stability across 100 Louvain seeds
  14_where.py              HPA location, MGI developmental lethality, AP vs AR lethality
  15_bias_checks.py        study-intensity regression; genome-wide yeast screens only
  16_stages.py             GO functional categories (go-basic 2026-07-26; UniProt-GOA human 2026-10-11) and evolutionary depth
  17_figures2.py, 18_fig6.py   Figures 1-6
  19_supp_tables.py        Supplementary_Tables_S1-S8.xlsx
  20_autophagy_block.py    direction of effect of autophagy-core genes (run before 19)
  21_new_analyses.py       direction transfer: yeast RLS vs CLS, replication back-test and mouse predictions,
                           human-cell vs organismal direction by functional category (Tables S9, S10)
  22_fig_transfer.py       Figure 3 (direction transfer)

Changes from version 2 (19 October 2026)
  - Fly, worm and mouse genes are now mapped to orthologs by database identifier instead of gene symbol. GenAge
    symbols are partly outdated (e.g. fly Tor, Sir2, Sod, Akt1), and symbol matching had lost 42 of 202 fly and
    88 of 889 worm entries. Human-transgene entries in GenAge are assigned to that human gene.
  - Human ortholog targets are restricted to protein-coding genes (pseudogenes removed).
  - All downstream results, figures and tables were regenerated (116 core genes; 6 in all five systems).
  - Benjamini-Hochberg q-values added for direction concordance (S8b); autophagy-block table added (S8g).
  - With version-2 settings, the scripts reproduce version 2 exactly from the 22 October 2026 downloads.

Raw database downloads are not included because of size and licences; 00_download_data.sh retrieves them.
Later database releases may give slightly different numbers.

Changes from version 3 (28 October 2026)
  - New scripts 21 and 22 (direction-transfer analyses, Figure 3); new Tables S9 (180 mouse predictions) and S10.
  - Figure numbering in manuscript v8/v9: Fig1_design = Figure 1; Fig2_convergence = Figure 2; Fig3_transfer = Figure 3;
    Fig3_core_matrix = Figure 4; Fig4_network = Figure 5; Fig5_where_stages = Figure 6; Fig6_architecture = Figure 7.
  - Scripts 12-20 and their outputs are unchanged.

Changes from version 4
  - Figure panel letters changed to lowercase (Springer style) in Fig1/Fig2/Fig3_transfer/Fig5 scripts; Figure 1 labels
    revised (American spelling). Fig3_core_matrix, Fig4_network and Fig6_architecture are unchanged.
  - Manuscript figure numbering: Fig1_design = Fig. 1; Fig2_convergence = Fig. 2; Fig3_transfer = Fig. 3;
    Fig3_core_matrix = Fig. 4; Fig4_network = Fig. 5; Fig5_where_stages = Fig. 6; Fig6_architecture = Fig. 7.
