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A Pilot Metabolomic Study for Diagnosing Aspergillus Infection in Immunocompromised Pediatric Cancer Patients
Taghreed Khaled Abdelmoneim1, Asmaa Ramzy1, Mostafa Ahmed Zaki1
1Proteomics and Metabolomics Research Program, Basic Research Department, Children's Cancer Hospital Egypt, Cairo 57357, Egypt.
Abstract:
Fungal infection caused by invasive Aspergillus is a life-threatening complication in immunocompromised pediatric cancer patients. However, the early diagnosis of invasive infection remains a clinical challenge due to the lack of specific, non-invasive biomarkers. The current study investigates plasma metabolomic profiling integrated with an AI-derived fungal secondary metabolite database to identify potential biomarkers for rapid, non-invasive detection of Aspergillus infection. Plasma samples from thirteen pediatric oncology patients were analyzed using untargeted metabolomics based on UHPLC-MS/MS. Based on galactomannan assay results, three patients were classified as Aspergillus-Infected (AIC) and ten as non-infected controls (NPCs). An in-house custom database for secondary metabolites of fungi was incorporated to enhance metabolite annotation. Eight metabolites were found to be candidate biomarkers based on statistical significance, fold change, and biological relevance. In the AIC cohort, aflatoxin B1, aspergillimide, fumifungin, and uridine were found to be significantly elevated while citric acid presented a decrease. Multivariate analysis utilizing PCA and PLSDA showed distinct group separation. Moreover, sample size estimation indicates that a minimum of 25 participants would be needed in future studies for appropriate statistical power.
Insights
This study identifies potential biomarkers for early detection of invasive Aspergillus fungal infections in children with cancer. Metabolomics and AI analysis revealed specific fungal metabolites in infected patients, aiding non-invasive diagnosis.
Area of Science:
- Mycology
- Clinical Chemistry
- Computational Biology
Background:
- Invasive Aspergillus infection is a severe threat to immunocompromised pediatric cancer patients.
- Early diagnosis is difficult due to a lack of specific, non-invasive biomarkers.
- Current diagnostic methods for invasive fungal infections can be invasive or lack sensitivity.
Purpose of the Study:
- To identify novel, non-invasive biomarkers for the early detection of invasive Aspergillus infection in pediatric oncology patients.
- To integrate plasma metabolomic profiling with an AI-derived fungal secondary metabolite database.
- To explore the potential of metabolomics for rapid, non-invasive diagnosis of fungal infections.
Main Methods:
- Untargeted plasma metabolomic profiling using UHPLC-MS/MS on samples from pediatric oncology patients.
- Classification of patients into Aspergillus-Infected (AIC) and non-infected controls (NPCs) based on galactomannan assay.
- Utilized an in-house custom database of fungal secondary metabolites for enhanced metabolite annotation.
- Employed multivariate statistical analyses, including Principal Component Analysis (PCA) and Partial Least Squares Discriminant Analysis (PLSDA).
Main Results:
- Identified eight candidate biomarkers with statistical significance, fold change, and biological relevance.
- Significantly elevated levels of aflatoxin B1, aspergillimide, fumifungin, and uridine were observed in the AIC cohort.
- Citric acid levels were decreased in the AIC cohort compared to controls.
- Multivariate analysis demonstrated distinct separation between AIC and NPC groups, indicating diagnostic potential.
Conclusions:
- Plasma metabolomic profiling combined with an AI fungal database shows promise for identifying biomarkers of invasive Aspergillus infection.
- Candidate biomarkers such as aflatoxin B1 and aspergillimide could facilitate early, non-invasive diagnosis in at-risk pediatric populations.
- Future studies with a larger sample size (minimum 25 participants) are warranted to confirm these findings and establish robust diagnostic criteria.
