Biology subjects

Dragoumani, K.

Publications and source records attributed to Dragoumani, K..

5 recordsLinked to original sources

bioRxiv2022

DRDs and Brain Derived Neurotrophic Factor share a common therapeutic ground: A novel bioinformatic approach sheds new light towards pharmacological treatment of Cognitive and Behavioral Disorders.

Cognitive and behavioral disorders are subgroups of mental health disorders. Both cognitive and behavioral disorders can occur in people of different ages, genders, and social backgrounds and they can cause serious physical, mental or social problems. The risk factors for these diseases are numerous, with a range from genetic and epigenetic factors to physical factors. In most cases, the appearance of such a disorder in an individual is a combination of his genetic profile and environmental stimuli. To date, researchers have not been able to identify the specific causes of these disorders and as such, there is urgent need for innovative study approaches. The aim of the present study was to identify the genetic factors which seem to be more directly responsible for the occurrence of a cognitive and/or behavioral disorder. More specifically, through bioinformatics tools and software as well as analytical methods such as systemic data and text mining, semantic analysis, and scoring functions, we extracted the most relevant single nucleotide polymorphisms (SNPs) and genes connected to these disorders. All the extracted SNPs were filtered, annotated, classified, and evaluated in order to create the "genomic grammar" of these diseases. The identified SNPs guided the search for top suspected genetic factors, dopamine receptors D and Neurotrophic Factor BDNF, for which regulatory networks were built. The identification of the "genomic grammar" and underlying factors connected to cognitive and behavioral disorders can aid the successful disease profiling, the establishment of novel pharmacological targets and provide the basis for personalized medicine, which takes into account the patients genetic background as well as epigenetic factors.

bioinformatics↗

bioRxiv2022

ADRA2B and HTR1A: An updated study of the biogenic amine receptors reveals novel conserved motifs which play key role in Mental Disorders.

Mental disorders are strongly connected with several psychiatric conditions including depression, bipolar disorder, schizophrenia, eating disorder and suicides. There are many biological conditions and pathways that define these complicated illnesses. For example, eating disorders are complex mental health conditions that require the intervention of geneticists, psychiatrists and medical experts in order to alleviate their symptoms. A patient with suicidal ideation should first be identified and consequently monitored by a similar team of specialists. Both genetics and epigenetics can shed light on eating disorders and suicides as they are found in the main core of such investigations. In the present study, an analysis has been performed on two specific members of the GPCR family towards drawing conclusions regarding their functionality and implementation in mental disorders. Specifically, evolutionary and structural studies on the adrenoceptor alpha 2b (ADRA2B) and the 5-hydroxytryptamine receptor 1A (HTR1A) have been carried out. Both receptors are classified in the biogenic amine receptors sub-cluster of the GPCRs and have been connected in many studies with mental diseases and malnutrition conditions. The major goal of this study is the investigation of conserved motifs among biogenic amine receptors that play an important role in this family signaling pathway, through an updated evolutionary analysis and the correlation of this information with the structural features of the HTR1A and ADRA2B. Furthermore, structural comparison of ADRA2B, HTR1A, and other members of GPCRs related with mental disorders is performed.

bioinformatics↗

bioRxiv2022

An updated evolutionary and structural study of TBK1 reveals highly conserved motifs as potential pharmacological targets in neurodegenerative diseases.

TANK binding kinase 1 protein (TBK1) is a kinase that belongs to the I{kappa}B (IKK) family. TBK1, also known as T2K, FTDALS4, NAK, IIAE8 and NF-{kappa}B, is responsible for the phosphorylation of the amino acid residues Serine and Threonine. This enzyme is involved in various key biological processes, including interferon activation and production, homeostasis, cell growth, autophagy, insulin production and the regulation of TNF-, IFN-{beta} and IL-6. Mutations in the TBK1 gene alter the proteins normal function and may lead to an array of pathological conditions, including disorders of the Central Nervous System. The present study sought to elucidate the role of the TBK1 protein in Amyotrophic Lateral Sclerosis (ALS), a human neurodegenerative disorder. A broad evolutionary and phylogenetic analysis of TBK1 was performed across numerous organisms to distinguish conserved regions important for the proteins function. Subsequently, mutations and SNPs were explored and their potential effect on the enzymes function was investigated. These analytical steps, in combination with the study of the secondary, tertiary, and quaternary structure of TBK1, enabled the identification of conserved motifs, which can function as novel pharmacological targets and inform therapeutic strategies for Amyotrophic Lateral Sclerosis.

bioinformatics↗

bioRxiv2022

A genomic study of the Japanese population focusing on the glucocorticoid receptor interactome highlights distinct genetic characteristics associated with stress response

All living organisms have been programmed to maintain a complex inner equilibrium called homeostasis, despite numerous adversities during their lifespan. Any threatening or perceived as such stimuli for homeostasis is termed a stressor, and a highly conserved response system called the stress response system has been developed to cope with these stimuli and maintain or reinstate homeostasis. The glucocorticoid receptor, a transcription factor belonging to the nuclear receptors protein superfamily, has a major role in the stress response system, and research on its interactome may provide novel information regarding the mechanisms underlying homeostasis maintenance. A list of 149 autosomal genes which have an essential role in GR function or are prime examples of GRE-containing genes was composed in order to gain a comprehensive view of the GR interactome. A search for SNPs on those particular genes was conducted on a dataset of 3.554 Japanese individuals, with mentioned polymorphisms being annotated with relevant information from the ClinVar, LitVar, and dbSNP databases. Forty-two SNPs of interest and their genomic locations were identified. These SNPs have been associated with drug metabolism and neuropsychiatric, metabolic, and immune system disorders, while most of them were located in intronic regions. The frequencies of those SNPs were later compared with a dataset consisting of 1465 Korean individuals in order to find population-specific characteristics based on some of the identified SNPs of interest. The results highlighted that rs1043618 frequencies were different in the two populations, with mentioned polymorphism having a potential role in chronic obstructive pulmonary disease in response to environmental stressors. This SNP is located in the HSPA1A gene which codes for an essential GR co-chaperone, and such information showcases that similar gene may be novel genomic targets for managing or combatting stress-related pathologies.

bioinformatics↗

bioRxiv2022

Semantic and population analysis of the genetic targets related to COVID-19 and its association with genes and diseases

SARS-CoV-2 is a coronavirus responsible for one of the most serious, modern worldwide pandemics, with lasting and multi-faceted effects. By late 2021, SARS-CoV-2 has infected more than 180 million people and has killed more than 3 million. The virus gains entrance to human cells through binding to ACE2 via its surface spike protein and causes a complex disease of the respiratory system, termed COVID-19. Vaccination efforts are being made to hinder the viral spread and therapeutics are currently under development. Towards this goal, scientific attention is shifting towards variants and SNPs that affect factors of the disease such as susceptibility and severity. This genomic grammar, tightly related to the dark part of our genome, can be explored through the use of modern methods such as natural language processing. We present a semantic analysis of SARS-CoV-2 related publications, which yielded a repertoire of SNPs, genes and disease ontologies. Population data from the 100Genomes Project were subsequently integrated into the pipeline. Data mining approaches of this scale have the potential to elucidate the complex interaction between COVID-19 pathogenesis and host genetic variation; the resulting knowledge can facilitate the management of high-risk groups and aid the efforts towards precision medicine.

bioinformatics↗