Aging research has largely focused on changes in protein expression levels, but aging cannot be explained by abundance changes alone. Here we focus on an under-explored dimension: structural changes in proteins and the dynamics of their interaction networks. In this study, we integrated experimental proteomics with computational structural biology to comprehensively characterize the age-dependent structural dynamics of plasma proteins — that is, how plasma proteins change structurally over a healthy life course.
Data_preprocessing_for_PAR.R Computes the Peak Area Ratio (PAR) for each ion, using the 6 ions from the 1st, 2nd, and 3rd precursors of peptide-03 among the internal standards (IS), in order to select the IS used for normalization. (Fig. 1B — code added 2025-10-19)
PAR_distribution_histogram.R Applies a log10 transformation to the PAR1–6 values obtained above and plots their distribution as a histogram, together with the corresponding CV values. (Fig. 1A, C — code added 2025-10-19)
PAR_input_preprocessing.R
Aging_log_norm_data_preprocessing.ipynb
PAR_data_preprocessing_Jhyh.R Preprocesses the data required for the downstream analyses.
Data_preprocessing_Jhyh+cosine similarity.R Performs cosine similarity analysis on the preprocessed data. (Fig. 2A, B)
limma_test_Jh_revised_added_fit3_final.R Uses limma to extract only the ions satisfying the fold-change and p-value criteria for each pattern, and plots the mean PAR change per pattern. (Fig. 3A, B)
overlap_pattern_fit3_final.R Merges the cosine similarity and limma results and retains only the overlapping ions.
overlap_boxplot_fit3_final.R Generates boxplots for each ion, grouped by pattern. (Fig. 3C)
pymol_interaction_distance.txt When inspecting AlphaFold3 multimer results in PyMOL, measures the minimum distance across the peptide– and protein–interface within each pattern's protein complex (1:1).
pymol_mean_plddt.txt When inspecting AlphaFold3 multimer results in PyMOL, computes the mean pLDDT. (Fig. 6B, C, D)
Cytoscape: Full STRING network, confidence ≥ 0.7, Homo sapiens (see manual for details). AF3 multimer web server: For PTMs, only N-linked glycosylation sites were added as NAG.