preprints.org > biology and life sciences > biophysics > doi: 10.20944/preprints202408.1424.v1 (registering DOI)

Preprint Article Version 1 This version is not peer-reviewed

Version 1 : Received: 18 August 2024 / Approved: 20 August 2024 / Online: 21 August 2024 (04:27:25 CEST)

The intricate relationship between genomic mutations and proteomic network topology represents a frontier in understanding cellular resilience and disease mechanisms. This study presents a novel approach to analyzing how proteomic topological structures evolve and potentially break down in response to accumulating genomic mutations, offering insights into the complex interplay between genetic alterations and protein interaction networks. We developed a computational model simulating a network of ten key proteins (A-J) over 20 discrete time points, each representing a state of increasing genomic mutation load. Our model incorporates dynamic protein interaction strengths that fluctuate in response to simulated genomic alterations and a topological representation of the protein network, allowing for visualization of structural changes. Not forgetting a quantitative measure of network integrity, correlating with the system's ability to maintain function under mutational stress. Our Key findings include: visualization of proteomic network evolution through a series of topological graphs, revealing how genomic mutations progressively alter protein interaction patterns and identification of a critical "breakage point" in the network topology, signifying a threshold where genomic mutations overwhelm the protein network's ability to maintain its functional structure. And also quantification of network properties, including interaction strengths and overall network density, demonstrating the non-linear relationship between genomic mutations and proteomic topological integrity.The observed breakage point may represent a critical threshold in disease progression, where the accumulation of genomic mutations leads to a collapse in the proteomic interaction network, potentially triggering pathological states. This methodology offers a new perspective on the genotype-phenotype relationship, viewing it through the lens of protein network topology. Our approach provides a framework for future studies to analyze how specific genomic mutations might impact proteomic structures, potentially leading to new insights in cancer research, neurodegenerative disorders, and other mutation-driven diseases. It also suggests that maintaining proteomic topological integrity could be a key factor in cellular resilience against genomic instability.

Proteomics; Genomics; Differential Geometry; Topology

Biology and Life Sciences, Biophysics

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