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Updated: Dec 10, 2025
A Streamlined Approach for Mass Spectrometry-Based Proteomics Using Selected Tissue Regions
Published on: April 18, 2025
Fractional diffusion on the human proteome as an alternative to the multi-organ damage of SARS-CoV-2
1Instituto Universitario de Matemáticas y Aplicaciones, Universidad de Zaragoza, 50009 Zaragoza, Spain and ARAID Foundation, Government of Aragón, 50018 Zaragoza, Spain.
Abstract:
The coronavirus 2019 (COVID-19) respiratory disease is caused by the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), which uses the enzyme ACE2 to enter human cells. This disease is characterized by important damage at a multi-organ level, partially due to the abundant expression of ACE2 in practically all human tissues. However, not every organ in which ACE2 is abundant is affected by SARS-CoV-2, which suggests the existence of other multi-organ routes for transmitting the perturbations produced by the virus. We consider here diffusive processes through the protein-protein interaction (PPI) network of proteins targeted by SARS-CoV-2 as an alternative route. We found a subdiffusive regime that allows the propagation of virus perturbations through the PPI network at a significant rate. By following the main subdiffusive routes across the PPI network, we identify proteins mainly expressed in the heart, cerebral cortex, thymus, testis, lymph node, kidney, among others of the organs reported to be affected by COVID-19.
Insights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 by infecting cells via ACE2. This study reveals virus perturbations spread through protein-protein interaction networks, affecting organs like the heart and brain.
Area of Science:
- Virology
- Systems Biology
- Computational Biology
Background:
- Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2, utilizing the ACE2 enzyme for cell entry.
- COVID-19 causes multi-organ damage, partly due to widespread ACE2 expression.
- Discrepancies in organ damage despite ACE2 abundance suggest alternative viral transmission routes.
Purpose of the Study:
- To investigate diffusive processes within the protein-protein interaction (PPI) network as a potential multi-organ transmission route for SARS-CoV-2.
- To identify key pathways and proteins involved in the propagation of viral perturbations across the human interactome.
Main Methods:
- Analysis of diffusive processes on the SARS-CoV-2 protein-protein interaction (PPI) network.
- Identification of subdiffusive regimes governing perturbation propagation.
- Mapping of identified pathways to affected organs based on protein expression data.
Main Results:
- A subdiffusive regime was identified, enabling significant propagation rates of viral perturbations through the PPI network.
- Key subdiffusive routes were mapped, highlighting proteins predominantly expressed in affected organs.
- Identified proteins are highly expressed in the heart, cerebral cortex, thymus, testis, lymph nodes, and kidneys, among other organs impacted by COVID-19.
Conclusions:
- The protein-protein interaction network provides an alternative route for SARS-CoV-2 perturbations to spread across multiple organs.
- Subdiffusive processes within the PPI network are critical for understanding COVID-19's multi-organ pathology.
- This network-based approach aids in identifying key molecular players and potential therapeutic targets in COVID-19 pathogenesis.
