ORIGINAL RESEARCH article
Front. Neurosci.
Sec. Neurogenomics
Volume 19 - 2025 | doi: 10.3389/fnins.2025.1572243
Spectral divergence prioritizes key classes, genes, and pathways shared between substance use disorders and cardiovascular disease its comorbidity
Provisionally accepted- 1School of Engineering and Computer Science, Baylor University, Waco, United States
- 2Department of Biology, College of Arts and Science, Baylor University, Waco, Texas, United States
- 3Department of Math and Computer Science, Belmont University, Nashville, Tennessee, United States
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Introduction: Substance use disorders (SUDs) are heterogeneous diseases with overlapping biological mechanisms and often present with co-occurring disease, such as cardiovascular disease (CVD). Gene networks associated with SUDs also implicate additional biological pathways and may be used to stratify disease subtypes. Node and edge arrangements within gene networks impact comparisons between classes of disease, and connectivity metrics, such as those focused on degrees, betweenness, and centrality, do not yield sufficient discernment of disease network classification. Comparatively, the graph spectrum's use of comprehensive information facilitates hypothesis testing and inter-disease clustering by using a larger range of graph characteristics. By adding a connectivity-based method, network rankings of similarity and relationships are explored between classes of SUDs and CVD.Methods: Graph spectral clustering's utility is evaluated relative to commonly used network algorithms for discernment between two distinct co-occurring disorders and capacity to rank pathways based on their distinctiveness. A collection of graphs' structures and connectivity to functionally identify the relationship between CVD and each of four classes of SUDs, namely alcohol use disorder (AUD), cocaine use disorder (CUD), nicotine use disorder (NUD), and opioid use disorder (OUD) is evaluated. Moreover, a Kullback-Leibler (KL) divergence is implemented to identify maximally distinctive genes (D^g). The emphasis of genes with high D^g enables a Jaccard similarity ranking of pathway distinctiveness, creating a functional "network fingerprint."Results: Spectral graph outperforms other connectivity-based approaches and reveals interesting observations about the relationship among SUDs. Between CUD and CVD, the gammaaminobutyric acidergic and arginine metabolism pathways are distinctive. The neurodegenerative prion disease and tyrosine metabolism are emphasized between OUD and CVD. The graph spectrum between AUD and NUD to CVD is not significantly divergent.Conclusion: Graph spectral clustering with KL divergence illustrates differences among SUDs with respect to their relationship to CVD, suggesting that despite a high-level co-occurring diagnosis or comorbidity, the nature of the relationship between SUD and CVD varies depending on the substance involved. The graph clustering method simultaneously provides insight into the specific biological pathways underlying these distinctions and may reveal future basic and clinical research avenues into addressing the cardiovascular sequelae of SUD.
Keywords: disease-associated prioritization, substance use disorder, cardiovascular disease, Graph spectrum, Functional fingerprint
Received: 06 Feb 2025; Accepted: 02 Jul 2025.
Copyright: © 2025 Castaneda and Baker. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Everest Uriel Castaneda, School of Engineering and Computer Science, Baylor University, Waco, United States
Erich J Baker, Department of Math and Computer Science, Belmont University, Nashville, 37212, Tennessee, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.