AI & Systems Bioinformatics Unit – University of Cyprus: Advancing Bioinformatics research in Cyprus, Europe, and beyond
The AI & Systems Bioinformatics Unit, established in 2023 and led by Dr. Anna Onisiforou, is based at the University of Cyprus within the Translational Neuropharmacology Laboratory (Zanos Lab). The unit develops computational approaches that integrate artificial intelligence, machine learning, systems biology, and computational modelling to investigate complex biological systems and human disease. Its research focuses on translating large-scale biological data into mechanistic insights and computational frameworks that support translational biomedical research, therapeutic discovery, and the identification of potential treatment strategies. The unit collaborates with researchers and clinicians across Europe, the United States, and internationally, advancing interdisciplinary research at the intersection of neuroscience, immunology, infectious disease biology, and pharmacology.
Our AI & System Bioinformatics Unit is a highly inter-disciplinary research unit supporting:
- drug repurposing
- in silico drug modeling
- molecular docking
- network analysis
- multi-omics analysis
- single-cell analysis
- machine learning
- deep learning
- clinical bioinformatics
- chemoinformatics
- immunoinformatics
- pathogen-host interactions analysis
In our pursuit, we are utilizing state-of-the-art High-Performance Computing (HPC), facilitating efficient handling and comprehensive analysis of extensive, complex biological datasets.
We are happy to offer our Systems Bioinformatics expertise to collaborating investigators. For collaboration inquiries, please contact Dr. Anna Onisiforou at onisiforou.anna@ucy.ac.cy
Head of the AI & Systems Bioinformatics Unit
Dr. Anna Onisiforou, BA, BSc, MSc, MSc, Ph.D.
Dr. Onisiforou holds a B.Sc. (Hons) in Natural Sciences with direction in Biology and Chemistry, a M.Sc. in Medicinal Chemistry, and a Ph.D. in Neuroscience. She also holds a B.A. (Hons) in Accounting and Finance and a M.Sc. in Finance and Financial Law.
Dr. Onisiforou completed her Ph.D. in Neuroscience, at The Cyprus Institute of Neurology & Genetics, hosted in the Bioinformatics Department, from 2018 to 2022. During her doctoral research, she conceptualized and developed systems bioinformatics approaches to investigate the interplay between viral infections and host biological processes, particularly in the context of neurodegenerative diseases. Her work introduced network-based methodologies integrating virus–host protein interactions, molecular mimicry, and microbiota–virus interactions to explore how pathogenic mechanisms may contribute to neurological and immune-related disorders
Her research established computational frameworks for studying pathogen-host interactions and their potential role in complex diseases, including neurodegenerative, autoimmune, and neuropsychiatric conditions.
Dr. Onisiforou’s achievements extend beyond her Ph.D. studies. Since 2023, she has served as Senior Scientist and Head of the AI & Systems Bioinformatics Unit, which she established within the Translational Neuropharmacology Laboratory at the University of Cyprus, advancing research at the intersection of computational and experimental neuroscience.
She is currently the Principal Investigator of the ImmUnoForecastMS project, funded by the Research and Innovation Foundation of Cyprus, which integrates artificial intelligence, computational modeling, and experimental approaches to map Epstein–Barr virus–induced immune dysregulation in Multiple Sclerosis and identify precision drug repurposing strategies and personalized therapeutic interventions. She is also Co-Principal Investigator of the ALZ-RISK project, funded by the Infectious Diseases Society of America (IDSA), investigating sex-specific viral mechanisms contributing to Alzheimer’s disease risk. In addition, she serves as co-investigator and co-applicant on multiple interdisciplinary research grants combining computational and experimental approaches to study brain disorders, including neurodegenerative and neuropsychiatric conditions, as well as systems pharmacology and therapeutic discovery.
Research Highlights
Predictive Network Pharmacology Model Anticipated the Limited Efficacy of Ozempic (Semaglutide) in Alzheimer’s Disease Before Clinical Trial Results
A recent study led by Dr. Onisiforou demonstrated how systems bioinformatics modeling can anticipate clinical trial outcomes before results become available. In work first released as a preprint in March 2025 and later published in Communications Medicine (Nature Portfolio), a computational network pharmacology model developed by Dr. Onisiforou and colleagues predicted that semaglutide would have limited therapeutic impact in Alzheimer’s disease (AD), ranking it among the lowest-impact diabetes therapies for AD prevention due to minimal engagement with core neurodegenerative pathways. This prediction was made months before the results of the EVOKE and EVOKE+ Phase III clinical trials were publicly reported in October and November 2025, which later confirmed that semaglutide did not slow cognitive or clinical decline in patients with AD. These findings illustrate how systems bioinformatics can help evaluate therapeutic hypotheses early and guide drug development decisions before costly clinical trials are completed.
Preprint: https://www.biorxiv.org/content/10.1101/2025.03.14.643306v1.abstract
Published article: https://www.nature.com/articles/s43856-026-01471-3
Recent Computational Frameworks Developed by the Unit
VirTrack — Mapping Viral Dynamics Across Disease Stages
VirTrack is a systems bioinformatics framework developed by Dr. Anna Onisiforou and published as a preprint in October 2025. The framework is designed to infer the influence of viral infections on host molecular pathways by integrating virus–host protein–protein interaction (PPI) networks with disease-specific transcriptomic data. Unlike traditional static network approaches, VirTrack enables a disease-stage–resolved analysis of how viral proteins perturb host biological processes. In its primary application, VirTrack was used to investigate the role of Epstein–Barr virus (EBV) across different clinical types of Multiple Sclerosis (MS), revealing stage-dependent patterns of viral influence on host molecular networks. By identifying viral–host interactions and pathways associated with distinct disease stages, the framework provides a computational strategy for stage-tailored therapeutic targeting. VirTrack supports the development of precision antiviral and immunomodulatory strategies that account for evolving virus–host dynamics throughout disease progression. While initially applied to Multiple Sclerosis, the framework is designed to be generalizable for investigating viral contributions to a broad range of complex human diseases.
Preprint: https://www.biorxiv.org/content/10.1101/2025.11.03.686445v1.abstract
VirTarget — Pioneering Virus-Informed Pharmacogenomics for MS
VirTarget is a virus-informed pharmacogenomics framework developed by Dr. Anna Onisiforou and colleagues from the USA and published as a preprint in 2025. The framework evaluates how MS immunotherapies interact with EBV–driven disease mechanisms by integrating EBV–host protein interaction networks, MS genetic susceptibility loci, and drug-induced transcriptomic responses. VirTarget addresses a central challenge in MS treatment, the “immunosuppression paradox”, where therapies are selected for immune suppression without considering their effects on viral biology. By classifying therapies as “reversers” (counteracting EBV-driven dysregulation) or “reinforcers” (potentially supporting viral pathways), the framework reveals how different drugs engage with virus-associated molecular networks. By identifying therapies that most effectively counteract EBV-related dysregulation, VirTarget moves MS therapy beyond a one-size-fits-all immunosuppression model toward virus-informed precision medicine, providing a roadmap for selecting treatments based on a patient’s viral and genetic profile and guiding the development of future immunotherapies that suppress disease without giving the underlying virus a biological advantage.
Other members of the Unit
Dr. Eleftheria Charalambous, BSc, MSc, Ph.D.
Josefina Ahmed
Team Members (more details in the Team Members section)
Publications (Selected)
- Onisiforou, A. (2026) The Immunosuppression Paradox in Multiple Sclerosis: Are We Fueling the Fire by Suppressing Immunity in an Epstein-Barr Virus-Linked Disease? Open forum Infectious Diseases, https://doi.org/10.1093/ofid/ofag097.
- Georgiou, P., Altas, B., Onisiforou, M., Zanos, P., Onisiforou, A. (2026). From Heatwaves to Brainwaves: Climate-Driven Microplastics Promote Epstein–Barr Virus Reactivation and Female-Biased Risk for Alzheimer’s Disease and Multiple Sclerosis, Research Square (pre-print). https://doi.org/10.21203/rs.3.rs-8928857/v1.
- Georgiou, N.A., Zanos, P., Onisiforou, A. (2026) Metformin provides superior neuroprotective potential compared to semaglutide in preventing diabetes-associated Alzheimer’s disease via dual actions. Communications Medicine. https://doi.org/10.1038/s43856-026-01471-3.
- Altas, B., Onisiforou, M., Zanos, P., Onisiforou, A. VirTarget: Virus-Informed Pharmacogenomics Framework Identifies Immunotherapies That Mitigate Epstein–Barr Virus–Driven Dysregulation in Multiple Sclerosis, bioRxiv, 2025. https://doi.org/10.1101/2025.11.03.686445.
- Onisiforou, A. VirTrack: A Framework for Inferring Viral Influence on Disease–Associated Transcriptomes — Clinical Type–Specific Epstein–Barr Virus Pathogenesis in Multiple Sclerosis, bioRxiv, 2025. https://doi.org/10.1101/2025.10.05.680499.
- Onisiforou, A., Koumas, M., Michael, A., Zanos, P. Selective transcriptomic recovery by (2R,6R)-hydroxynorketamine in opioid-abstinent mice: Machine learning identifies predictive biomarkers. bioRxiv. 2025. https://doi.org/10.1101/2025.06.04.657935.
- Onisiforou, A., Charalambous, E., Zanos, P. Shattering the Amyloid Illusion: The Microbial Enigma of Alzheimer’s Disease Pathogenesis—From Gut Microbiota and Viruses to Brain Biofilms. Microorganisms. 2025, 13(1), 90. https://doi.org/10.3390/microorganisms13010090
- Onisiforou, A., Zanos, P. One path, two solutions: Network-based analysis identifies targetable pathways for the treatment of comorbid type II diabetes and neuropsychiatric disorders, Computational & Structural Biotechnology Journal, 2024, 23, 3610-3624. https://doi.org/10.1016/j.csbj.2024.10.011
- Onisiforou, A., Zanos, P. Network-Based Analysis Identifies Targetable Pathways in Comorbid Type II Diabetes and Neuropsychiatric Disorders, bioRxiv, 2024, 06.25.600630. https://doi.org/10.1101/2024.06.25.600630.
- Onisiforou, A., Zanos, P.,Georgiou, P. Molecular signatures of premature aging in major depression and substance use disorders. Scientific Data, 2024, 11, 968. https://doi.org/10.1038/s41597-024-03538-z
- Onisiforou, A., Zanos, P. From viral infections to Alzheimer’s Disease: Unveiling the mechanistic links through Systems Bioinformatics. Journal of Infectious Diseases, 2024, 230, S128–S140. https://doi.org/10.1093/infdis/jiae242.
- Onisiforou A., Zanos P. From Viral Infections to Alzheimer’s Disease: Unveiling the Mechanistic Links Through Systems Bioinformatics. bioRxiv (2023), 12.05.570187. https://doi.org/10.1101/2023.12.05.570187.
- Christodoulou C*, Onisiforou A*, Zanos P, Zamba-Papanicolaou E. Unraveling the transcriptomic signatures of Parkinson’s Disease and Major Depression using single-cell and bulk data. Frontiers Aging Neuroscience (2023) 15. *Equal Contribution. https://doi.org/10.3389/fnagi.2023.1273855.
- Onisiforou A, Spyrou GM. Systems Bioinformatics Reveals Possible Relationship between COVID-19 and the Development of Neurological Diseases and Neuropsychiatric Disorders. Viruses (2022) 14:2270. https://doi.org/10.3390/v14102270.
- Onisiforou A, Spyrou GM. Immunomodulatory effects of microbiota-derived metabolites at the crossroad of neurodegenerative diseases and viral infection: network-based bioinformatics insights. Frontiers in Immunology (2022) 13. https://doi.org/10.3389/fimmu.2022.843128.
- Onisiforou A, Spyrou GM. Identification of viral-mediated pathogenic mechanisms in neurodegenerative diseases using network-based approaches. Briefings in Bioinformatics (2021) 22. https://doi.org/10.1093/bib/bbab141.
- Tomazou M., Bourdakou M.M., Minadakis G., Zachariou M., Oulas A., Karatzas E., Loizidou E.M., Kakouri A.C., Christodoulou C.C., Savva K., Zanti M., Onisiforou A., et al. Multi-omics data integration and network-based analysis drives a multiplex drug repurposing approach to a shortlist of candidate drugs against COVID-19. Briefings in Bioinformatics (2021) 22: https://academic.oup.com/bib/article/22/6/bbab114/6224262?login=false
Current Collaborations in Cyprus, Europe and beyond
- Dr. Bekir Altas, Assistant Professor at the School of Medicine, Marquette University, USA – https://scholar.google.com/citations?user=kZvlPa8AAAAJ&hl=en
- Dr. Souvik Kar, Senior Scientist and Head of the International Neuroscience Institute Hannover, Germany.
- Dr. Eva Faurobert, co-leads the INVADE team at the Institute for Advanced Biosciences IAB, INSERM, France – https://scholar.google.com/citations?user=VGvpBg0AAAAJ&hl=fr
- Prof. Johaness Hertel, Professor (W1) in Systems Biology and Transnational Psychiatry, Department of Psychiatry ad Psychotherapy, University Medicine Greifswald – https://www2.medizin.uni-greifswald.de/psych/ueber-uns/leitungmitarbeiter/johannes-hertel/
- Dr. Polymnia Georgiou, Assistant Professor of Neuroscience and Endocrinology, University of Cyprus, Cyprus and University of Wisconsin-Milwaukee, USA – https://polymniageo.wixsite.com/georgioulab
- PD Dr. med. Fabian Frost, Clinician Scientist at Department of Medicine A, University Medicine Greifswald, Germany – https://scholar.google.de/citations?user=R90o5jwAAAAJ&hl=de
- Dr. Christiana Christodoulou, Senior Scientist, Neuroepidemiology Department, Cyprus Institute of Neurology and Genetics – https://scholar.google.com/citations?user=txcJxewAAAAJ&hl=en
- Prof. Eleni Zamba Pananicolaou, Head of Neuroepidemiology Department and EMG Laboratory, Senior Consultant Neurologist, Cyprus Institute of Neurology and Genetics – https://www.cing.ac.cy/easyconsole.cfm/id/258
AI & Systems Bioinformatics Unit: Secured Grants
| Grant Acronym | Grant Title | Funding Agency | Principal Investigator | Funding Amount |
|---|---|---|---|---|
| ALZHEIMER | Identification of viral-mediated pathogenic mechanisms in comorbid Alzheimer’s Disease and Major Depression using Systems Bioinformatics | Infectious Diseases Society of America (IDSA, USA) | Dr. Anna Onisiforou; co-PI: Dr. Panos Zanos | €96,941 |
| ALZ-RISK | Sex-Specific Mechanisms of HSV-1 and EBV in Alzheimer’s Disease Risk | Infectious Diseases Society of America (IDSA, USA) | Dr. Anna Onisiforou; co-PI: Dr. Panos Zanos | €100,000 |
| ImmUnoForecastMS | Integrative Systems Biology to Map Epstein–Barr Virus– Induced Immune Dysregulation in Multiple Sclerosis for Precision Drug Repurposing and Personalized Intervention | Research and Innovation Foundation Cyprus | Dr. Anna Onisiforou | €100,000 |


