SAINS MALAYSIANA

Sains Malaysiana 55(12)(2025): 103-116

http://doi.org/10.17576/jsm-2026-5501-08

Topological Analysis of Age-Related Proteins in Protein-Protein Interaction Networks via Local Persistent Homology

(Analisis Topologi Protein Berkaitan Umur dalam Rangkaian Interaksi Protein-Protein melalui Homologi Berterusan Tempatan)

ABDUL SYUKOR HAZRAM, SAKHINAH ABU BAKAR* & FATIMAH ABDUL RAZAK

Department of Mathematical Science, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor, Malaysia

Diserahkan: 8 November 2024/Diterima: 25 Disember 2025

Abstract

Ageing is a complex biological process that gradually alters cellular function and patterns of protein interaction. Standard network-based measures such as degree, betweenness and clustering coefficient are widely used in protein–protein interaction networks (PPINs), but these metrics may overlook subtle changes within local neighbourhoods. This study applies Local Persistent Homology (LPH) to characterise age-related differences in the local topology of PPINs, providing structural information that is not captured through global or node-level analyses. For each protein, a level 2 ego network is constructed and its and features are summarised using persistence diagrams (PDs). The Wasserstein distance between PDs from adult and elderly networks is then computed to quantify topological variation across age groups. The Wasserstein distance for each protein was compared with its degree, betweenness, and local clustering coefficient to examine how local topological structure relates to standard centrality measures. Proteins with many topological components tend to exhibit higher degree and betweenness but lower clustering, while proteins in simpler neighbourhoods show longer average persistence and more stable structural patterns. By integrating LPH results with gene-disease association data, 25 proteins with notable age-related topological differences are identified, including several associated with neurodegenerative diseases. Overall, LPH deepens the analysis of PPIN architecture by exposing subtle, age-linked structural patterns that remain undetected using network centralities.

Keywords: Ageing; local persistent homology; network centrality

Abstrak

Penuaan merupakan suatu proses biologi kompleks yang mengubah fungsi sel dan corak interaksi protein secara beransur-ansur. Pengukuran rangkaian sedia ada seperti pemusatan darjah, pengantaraan dan pekali gugusan tempatan digunakan dalam rangkaian interaksi protein–protein (RIPP), namun metrik ini mungkin tidak mampu menangkap perubahan halus yang berlaku dalam kejiranan tempatan. Kajian ini menggunakan Homologi Gigih Tempatan (HGT) untuk mencirikan perbezaan berkaitan usia dalam topologi tempatan RIPP, sekali gus menyediakan maklumat struktur yang tidak dapat ditangkap melalui analisis peringkat global atau nod. Bagi setiap protein, rangkaian ego aras 2 dibina dan ciri serta diringkaskan melalui rajah gigih (PD). Jarak Wasserstein antara PD bagi rangkaian dewasa dan warga emas kemudiannya dikira untuk mengukur variasi topologi merentas kumpulan umur. Nilai jarak Wasserstein bagi setiap protein dibandingkan dengan pemusatan darjah, pengantaraan dan pekali gugusan tempatan untuk menilai hubungan antara struktur topologi tempatan dan pengukuran rangkaian tempatan. Protein dengan komponen topologi yang tinggi cenderung mempunyai nilai pemusatan darjah dan pengantaraan yang lebih tinggi tetapi pekali gugusan yang lebih rendah, manakala protein dalam kejiranan yang lebih ringkas menunjukkan purata jangka hayat yang lebih panjang dan struktur yang lebih stabil. Dengan menggabungkan hasil HGT bersama data hubungan gen-penyakit, sebanyak 25 protein dikenal pasti menunjukkan perbezaan topologi berkaitan usia yang ketara, termasuk beberapa yang berkaitan dengan penyakit neurodegeneratif. Secara keseluruhannya, HGT memperkukuh analisis struktur RIPP dengan mendedahkan pola halus yang berkait dengan usia, yang tidak dapat dikesan menggunakan pemusatan rangkaian.

Kata kunci: Homologi gigih tempatan; pemusatan rangkaian; penuaan

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*Pengarang untuk surat-menyurat; email: p94850@siswa.ukm.edu.my