George M. Spyrou

Cyprus Institute of Neurology and Genetics · Bioinformatics Department

In this study, we developed and evaluated Machine Learning (ML) models aimed at predicting the stage of multiple myeloma (MM) and the progression of monoclonal gammopathy of undetermined significance (MGUS) to MM. Accurate staging of MM is critical for determining appropriate treatment strategies, and our models, employing algorithms such as Elasti...

Background/aim Multiple Myeloma is the second most common blood cancer, characterised by the accumulation of malignant plasma cells and the production of large amounts of a monoclonal immunoglobulin protein, in the bone marrow. The identification and progression/behaviour of molecular markers across stages remains a scientific challenge. This work...

Background The health benefits of the Mediterranean diet are partially attributed to the polyphenols present in extra virgin olive oil (EVOO), which have been shown to have anti-cancer properties. However, the possible effect that EVOO could have on Chronic Lymphocytic Leukemia (CLL) has not been fully explored. Methods This study investigates the...

In the area of drug research, several computational drug repurposing studies have highlighted candidate repurposed drugs, as well as clinical trial studies that have tested/are testing drugs in different phases. To the best of our knowledge, the aggregation of the proposed lists of drugs by previous studies has not been extensively exploited toward...

Prioritization or ranking of different cell types in a single-cell RNA sequencing (scRNA-seq) framework can be performed in a variety of ways, some of these include: i) obtaining an indication of the proportion of cell types between the different conditions under study, ii) counting the number of differentially expressed genes (DEGs) between cell t...

Immediate-early genes (IEGs) are a class of activity-regulated genes (ARGs) that are transiently and rapidly activated in the absence of de novo protein synthesis in response to neuronal activity. We explored the role of IEGs in genetic networks to pinpoint potential drug targets for Alzheimer’s disease (AD). Using a combination of network analysis...

The standard of care in Acute Myeloid Leukemia patients has remained essentially unchanged for nearly 40 years. Due to the complicated mutational patterns within and between individual patients and a lack of targeted agents for most mutational events, implementing individualized treatment for AML has proven difficult. We reanalysed the BeatAML data...

Background: The health benefits of the Mediterranean diet are partially attributed to the polyphenols present in extra virgin olive oil (EVOO), which have been shown to have anti-cancer properties. However, the possible effect that EVOO could have on Chronic Lymphocytic Leukemia (CLL) has not been fully explored. Methods: This study investigates t...

Motivation A common task in scientific research is the comparison of lists or sets of diverse biological entities such as biomolecules, ontologies, sequences and expression profiles. Such comparisons rely, one way or another, on calculating a measure of similarity either by means of vector correlation metrics, set operations such as union and inter...

Prioritization or ranking of different cell types in a scRNA-Seq framework can be performed in a variety of ways, some of these include: i) obtaining an indication of the proportion of cell types between the different conditions under study, ii) counting the number of differentially expressed genes (DEGs) between cell types and conditions in the ex...

In vivo SELEX is an advanced adaptation of Systematic Evolution of Ligands by Exponential Enrichment (SELEX) that allows the development of aptamers capable of recognizing targets directly within their natural microenvironment. While this methodology ensures a higher translation potential for the selected aptamer, it does not select for aptamers th...

Alzheimer's disease (AD) is an age-dependent neurodegenerative disorder and the most common cause of cognitive decline. The alarming epidemiological features of Alzheimer's disease, combined with the high failure rate of candidate drugs tested in the preclinical phase, impose more intense investigations for new curative treatments. NRF2 (Nuclear fa...

Niclosamide is a commonly used helminthicidic drug for the treatment of human parasitosis by helminths. Recently, efforts have been focusing on repurposing this drug for the treatment of other diseases, such as idiopathic pulmonary fibrosis. Subepithelial lung myofibroblasts (SELMs) isolated from tissue biopsies of patients undergoing surgery for l...

Bacterial Wars (BW) is a network-based tool that applies a two-step pipeline to display information on the competition of bacterial species found in the same microbiome. It utilizes antimicrobial peptide (AMP) sequence similarities to obtain a relationship between species. The working hypothesis (putative AMP defense) is that friendly species share...

Oct4 is a pioneer transcription factor regulating pluripotency. However, it is poorly known whether Oct4 has an impact on somatic cells. We generated OCT4 knockout clonal cell lines using immortalized human skin keratinocytes to identify a functional role for the protein. Here we report that Oct4-deficient cells transitioned into a mesenchymal-like...

Alzheimer’s disease (AD) is a progressive neurodegenerative disease and is the most common type of dementia. Although a considerably large amount of money has been invested in drug development for AD, no disease modifying treatment has been detected so far. In our previous work, we developed a computational method to highlight stage-specific candid...

In the area of drug research, several computational drug repurposing studies have highlighted candidate repurposed drugs, as well as drugs from clinical trial studies in different phases. To our knowledge, the aggregation of the proposed lists of drugs by previous studies has not been extensively exploited towards the generation of a dynamic refere...

Makorin RING finger protein 3 (MKRN3) is an important factor located on chromosome 15 in the imprinting region associated with Prader-Willi syndrome. Imprinted MKRN3 is expressed in hypothalamic regions essential for the onset of puberty and mutations in the gene have been found in patients with central precocious puberty. The pubertal process is l...

We draw from the assumption that similarities between pathogens at both pathogen protein and host protein level, may provide the appropriate framework to identify and rank candidate drugs to be used against a specific pathogen. Vir2Drug is a drug repurposing tool that uses network-based approaches to identify and rank candidate drugs for a specific...

Background Spastic ataxias (SAs) encompass a group of rare and severe neurodegenerative diseases, characterized by an overlap between ataxia and spastic paraplegia clinical features. They have been associated with pathogenic variants in a number of genes, including GBA2 . This gene codes for the non-lysososomal β-glucosylceramidase, which is involv...

The emerging high-throughput technologies have led to the shift in the design of translational medicine projects towards collecting multi-omics patient samples and, consequently, their integrated analysis. However, the complexity of integrating these datasets has triggered new questions regarding the appropriateness of the available computational m...

PathIN is a web-service that provides an easy and flexible way for rapidly creating pathway-based networks at several functional biological levels: genes, compounds and reactions. The tool is supported by a database repository of reference pathway networks across a large set of species, developed through the freely available information included in...

Coronavirus Disease 2019 (COVID-19) is associated with increased incidence of neurological diseases and neuropsychiatric disorders after infection, but how it contributes to their development remains under investigation. Here, we investigate the possible relationship between COVID-19 and the development of ten neurological disorders and three neuro...

Background Clinical classification of autistic patients based on current WHO criteria provides a valuable but simplified depiction of the true nature of the disorder. Our goal is to determine the biology of the disorder and the ASD-associated genes that lead to differences in the severity and variability of clinical features, which can enhance the...

Females are underrepresented in the science, technology, engineering, mathematics and medicine (STEMM) disciplines globally and although progress has been made, the gender gap persists. Our aim was to explore gender parity in the context of gender representation and internal collaboration at the Cyprus Institute of Neurology and Genetics (CING), a...

Bidirectional cross-talk between commensal microbiota and the immune system is essential for the regulation of immune responses and the formation of immunological memory. Perturbations of microbiome-immune system interactions can lead to dysregulated immune responses against invading pathogens and/or to the loss of self-tolerance, leading to system...

Osteoarthritis, the most common joint disorder, is characterised by deterioration of the articular cartilage. Many studies have identified potential therapeutic targets, yet no effective treatment has been determined. The aim of this study was to identify and rank osteoarthritis-associated genes and micro-RNAs to prioritise those most integral to t...

Muscular dystrophies are a group of rare and severe inherited disorders mainly affecting the muscle tissue. Duchene Muscular Dystrophy, Myotonic Dystrophy types 1 and 2, Limb Girdle Muscular Dystrophy and Facioscapulohumeral Muscular Dystrophy are some of the members of this family of disorders. In addition to the current diagnostic tools, there is...

Muscular dystrophies are a group of disorders that cause progressive muscle weakness. There is an increasing interest for the development of biomarkers for these disorders and specifically for Duchene Muscular Dystrophy. Limited research however, has been performed on the biomarkers’ development for the most rare muscular dystrophies, like the Faci...

Alzheimer’s disease (AD) is a progressive neurodegenerative disease and the most common type of dementia. With no disease-curing drugs available and an ever-growing AD-related healthcare burden, novel approaches for identifying therapies are needed. In this work, we propose stage-specific candidate repurposed drugs against AD by using a novel netwo...

Background This study aims to characterize SARS-CoV-2 mutations which are primarily prevalent in the Cypriot population. Moreover, using computational approaches, we assess whether these mutations are associated with changes in viral virulence. Methods We utilize genetic data from 144 sequences of SARS-CoV-2 strains from the Cypriot population obt...

Skeletal muscle growth and maintenance depend on two tightly regulated processes, myogenesis and muscle regeneration. Both processes involve a series of crucial regulatory molecules including muscle-specific microRNAs, known as myomiRs. We recently showed that four myomiRs, miR-1, miR-133a, miR-133b, and miR-206, are encapsulated within muscle-deri...

Background/aim: Colon cancer is one of the most common cancer types and the second leading cause of death due to cancer. Many efforts have been performed towards the investigation of molecular alterations during colon cancer progression. However, the identification of stage-specific molecular markers remains a challenge. The aim of this study was...

The predominance of bacterial taxa in the gut, was examined in view of the putative antimicrobial peptide sequences (AMPs) within their proteomes. The working assumption was that compatible bacteria would share homology and thus immunity to their putative AMPs, while competing taxa would have dissimilarities in their proteome-hidden AMPs. A network...

Introduction The pathogenesis of cutaneous T-cell lymphoma (CTCL) remains poorly understood and the histologic diagnosis of early MF is one of the most vexing problems in dermatopathology. Our aim was to apply state-of-the-art bioinformatic tools in order to unravel the mechanisms of CTCL pathobiology, to address new therapeutic possibilities as we...

Myotonic Dystrophy type 1 (DM1) is the most common adult-onset muscular dystrophy, primarily characterized by muscle wasting and weakness. Many biomarkers already exist in the rapidly developing biomarker research field which aim to improve patients’ care. Limited work, however, has been performed on rare diseases, including DM1. We have previously...

Goal: Most common diseases are influenced by multiple gene interactions and interactions with the environment. Performing an exhaustive search to identify such interactions is computationally expensive and needs to address the multiple testing problem. A four-step framework is proposed for the efficient identification of n-Way interactions. Methods...

Whole genome sequencing of viral specimens following molecular diagnosis is a powerful analytical tool of molecular epidemiology that can critically assist in resolving chains of transmission, identifying of new variants or assessing pathogen evolution and allows a real-time view into the dynamics of a pandemic. In Cyprus, the first two cases of CO...

A fundamental issue related to the understanding of the molecular mechanisms, is the way in which common pathways act across different biological experiments related to complex diseases. Using network-based approaches, this work aims to provide a numeric characterization of pathways across different biological experiments, in the prospect to create...

This study aims to characterize SARS-CoV-2 mutations which are primarily prevalent in the Cypriot population. Moreover, using computational approaches, we assess whether these mutations are associated with changes in viral virulence. We utilize genetic data from 144 sequences of SARS-CoV-2 strains from the Cypriot population obtained between March...

During the course of a viral infection, virus–host protein–protein interactions (PPIs) play a critical role in allowing viruses to replicate and survive within the host. These interspecies molecular interactions can lead to viral-mediated perturbations of the human interactome causing the generation of various complex diseases. Evidences suggest th...

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is undeniably the most severe global health emergency since the 1918 Influenza outbreak. Depending on its evolutionary trajectory, the virus is expected to establish itself as an endemic infectious respiratory disease exhibiting seasonal flare-ups. Therefore, despite the unpr...

Background Next-generation sequencing (NGS) represents a significant advancement in clinical genetics. However, its use creates several technical, data interpretation and management challenges. It is essential to follow a consistent data analysis pipeline to achieve the highest possible accuracy and avoid false variant calls. Herein, we aimed to co...

Fibrotic diseases cover a spectrum of systemic and organ-specific maladies that affect a large portion of the population, currently without cure. The shared characteristic these diseases feature is their uncontrollable fibrogenesis deemed responsible for the accumulated damage in the susceptible tissues. Idiopathic Pulmonary Fibrosis, an interstiti...

Whole genome sequencing of viral specimens following molecular diagnosis is a powerful analytical tool of molecular epidemiology that can critically assist in resolving chains of transmission, identifying of new variants or assessing pathogen evolution and allows a real-time view into the dynamics of a pandemic. In Cyprus, the first two cases of CO...

Despite their distinct clinical manifestation, frontal fibrosing alopecia (FFA) and lichen planopilaris (LPP) display similar histopathologic features. Aberrant innate immune responses to endogenous or exogenous triggers have been discussed as factors that could drive inflammatory cascades and the collapse of the stem cell niche. In this explorator...

Human skin and hair follicles are recognized sites of microbial colonization. These microbiota help regulate host immune mechanisms via an interplay between microbes and immune cells, influencing homeostasis and inflammation. Bacteria affect immune responses by controlling the local inflammatory milieu, the breakdown of which can result in chronic...

This study aims to highlight SARS-COV-2 mutations which are associated with increased or decreased viral virulence. We utilize genetic data from all strains available from GISAID and countries’ regional information, such as deaths and cases per million, as well as COVID-19-related public health austerity measure response times. Initial indications...

During the course of a viral infection, virus-host protein-protein interactions (PPIs) play a critical role in allowing viruses to evade host immune responses, replicate and hence survive within the host. These interspecies molecular interactions can lead to viral-mediated perturbations of the human interactome causing the generation of various com...

Background: Systems Medicine is a novel approach to medicine, i.e. an interdisciplinary field that considers the human body as a system, composed of multiple parts and of complex relationships at multiple levels, and further integrated into an environment. Exploring Systems Medicine implies understanding and combining concepts coming from diametral...

Signal transduction tasks as well as other complex biological processes involve many different changes in groups of genes, proteins, and metabolites linked together in chains or networks called pathways or networks of pathways. In a classical functional analysis, the biomolecules found to play a role in the biological status under investigation are...

In Cyprus, approximately 9% of triple-negative (estrogen receptor-negative, progesterone receptor-negative, and human epidermal growth factor receptor 2-negative) breast cancer (TNBC) patients are positive for germline pathogenic variants (PVs) in BRCA1/2. However, the contribution of other genes has not yet been determined. To this end, we aimed t...

Huntington's disease is a rare neurodegenerative disease caused by a cytosine-adenine-guanine (CAG) trinucleotide expansion in the Huntingtin (HTT) gene. Although Huntington's disease (HD) is well studied, the pathophysiological mechanisms, genes and metabolites involved in HD remain poorly understood. Systems bioinformatics can reveal synergistic...