Mechanisms Of Disease Development Research Articles

Enhancing Awareness and Management of Carpal Tunnel Syndrome Among Medical Professionals and Athletes

Introduction and objective: The objective of this research is to enhance the awareness of carpal tunnel among medical professionals and individuals engaged in sports. The acquired knowledge will enable medical professionals to more effectively identify, treat, and prevent issues related to carpal tunnel. Additionally, individuals engaged in sports will be able to prevent the occurrence of carpal tunnel syndrome in themselves or their pupils, thereby allowing them to engage in long-term and safe physical activity. Review methods: Review and summary of research studies available in open-source format on Google Scholar, PubMed. Abbreviated description of the state of knowledge: Carpal tunnel syndrome is a disease belonging to the group of compression neuropathies. The symptoms of carpal tunnel syndrome typically manifest as an uncomfortable sensation in the thumb, index finger, and half of the ring finger. Such symptoms may include numbness and tingling. In some cases, weakness of the hand muscles may occur, and in rarer instances, atrophy of the hand muscles. The condition of carpal tunnel syndrome is primarily the result of repetitive movements of the fingers and wrist. Such activities include typing, using a mouse, riding a bicycle, or playing a musical instrument. Summary: Carpal tunnel syndrome is a prevalent condition among the general population. This condition may affect individuals who engage in regular physical activity, resulting in diminished efficiency and a notable reduction in the quality of life. The objective of this study is to examine the risk factors, symptoms, and diagnostic methods associated with carpal tunnel syndrome. In the context of sports, we will examine the mechanisms of disease development in athletes and focus on prevention. This encompasses the rehabilitation of individuals at risk of developing the disease and patient education, which will facilitate the minimisation of the appearance or recurrence of disease symptoms.

P-335 Integrative analysis of endometriosis and adenomyosis through single-cell transcriptomics

Abstract Study question What are the shared and unique cell type -specific molecular pathways in endometriosis and adenomyosis? Summary answer Our analysis focuses on hormonal pathways and those regulating cell proliferation and apoptosis, which are crucial for the persistence of the lesions. What is known already Estrogen-driven proliferation and progesterone unresponsiveness are key mechanisms in the pathogenesis of endometriosis and adenomyosis. It has been recently observed that core pathways governing proliferation and apoptosis, such as the Wnt/beta-catenin and KRAS pathways, are involved in the etiology. The precise mechanisms of how estrogen and progesterone signaling interact with the Wnt/beta-catenin and KRAS pathways, which contribute to lesion growth maintenance, are not fully understood, but preliminary evidence suggests some level of cross-talk in both conditions. Study design, size, duration Although endometriosis and adenomyosis share similar mechanisms, they have mostly been studied in isolation. We propose a comprehensive study using an integrated approach to gain a deeper understanding of their pathophysiology. We will combine recent single-cell study data from both disorders, and examine the shared and unique cell-type-specific molecular pathways diverging from the eutopic endometrium. Participants/materials, setting, methods We will employ publicly available single-cell transcriptomic data from cases of endometriosis, adenomyosis, and controls with eutopic endometrium. Tissue sections from an extensive collection of patient samples will be examined for validation. Main results and the role of chance We will integrate single-cell transcriptomic data for endometriosis, adenomyosis, and eutopic endometrium controls. For each cell type, we will conduct comprehensive differential expression analysis between lesions and endometrium, study cell-to-cell communication among major cell types, and construct gene regulatory networks that are either shared or specific to endometriosis and adenomyosis. We will also consider GWAS lead genes and investigate their cell type-specific expression, focusing on hormonally regulated genes. Tissue sections of patient samples, apoptosis measurements, and clinical parameters including pain data will be utilized for validation. Limitations, reasons for caution The public single-cell transcriptomic data for endometriosis and adenomyosis have limitations in sample size and menstrual cycle distribution. The utilized single-cell transcriptomics data and the in-house tissue collections for validations studies are not matched. Wider implications of the findings This project aims to identify molecular pathways in endometriosis and adenomyosis, potentially revealing common disease development mechanisms and unique molecular signatures. Both endometriosis and adenomyosis are significant health issues affecting women, and their study contributes to the broader understanding of women’s health. Trial registration number not applicable

Decoding Organelle Interactions: Unveiling Molecular Mechanisms and Disease Therapies.

Organelles, substructures in the cytoplasm with specific morphological structures and functions, interact with each other via membrane fusion, membrane transport, and protein interactions, collectively termed organelle interaction. Organelle interaction is a complex biological process involving the interaction and regulation of several organelles, including the interaction between mitochondria-endoplasmic reticulum, endoplasmic reticulum-Golgi, mitochondria-lysosomes, and endoplasmic reticulum-peroxisomes. This interaction enables intracellular substance transport, metabolism, and signal transmission, and is closely related to the occurrence, development, and treatment of many diseases, such as cancer, neurodegenerative diseases, and metabolic diseases. Herein, the mechanisms and regulation of organelle interactions are reviewed, which are critical for understanding basic principles of cell biology and disease development mechanisms. The findings will help to facilitate the development of novel strategies for disease prevention, diagnosis, and treatment opportunities.

Supposed Virulence Factors of Flavobacterium psychrophilum: A Review

Flavobacterium psychrophilum is currently one of the most important pathogens in aquaculture worldwide, causing high losses to farmed salmonids particularly during early growth stages with significant economic impact. Despite previous attempts, no effective vaccine has been developed, and protection against introduction into farms is difficult due to the ubiquitous occurrence of the pathogen. A better understanding of the mechanism of disease development is essential for targeted therapeutic and preventive measures in farms. Unfortunately, the pathogenesis of diseases caused by F. psychrophilum has not been elucidated yet. Previously, several putative virulence factors have been identified. Some appear to be essential for disease development, while others are probably dispensable. The importance of some factors has not yet been explored. This review focuses on the supposed virulence factors of F. psychrophilum and the current knowledge about their importance in the pathogenesis of the disease.

Urticaria

The relevance of the disease is due to its prevalence ― for acute urticaria up to 20% with predominance in the paediatric population, for chronic spontaneous urticaria up to 0.5–5% of the population. The course of the disease is characterised by unpredictability of prognosis of duration, effectiveness of standard therapy, serious impact on the quality of life of the patient, his relatives, the burden on health authorities. The lack of accurate understanding of the mechanisms of disease development, a wide range of pathogenetic treatment complicates the possibility of rapid achievement of drug remission. The clinical Recommendations contain up-to-date information on epidemiology, pathogenesis, clinical picture, differential diagnosis, possibilities of examination and stage treatment, including immunobiological therapy. The procedure of medical care, prophylaxis and dispensary observation, criteria for assessing the quality of patient management and supporting material, including questionnaires to assess the severity of the condition and the effectiveness of treatment are outlined. Clinical recommendations on urticaria are intended for practicing physicians of all specialities, students, teachers of medical schools, residents, postgraduates and researchers.

Laboratory markers of depression: literature review

The search for laboratory markers of depression is currently a potential key to understanding the mechanisms of disease development, selecting personalized antidepressant therapy, and defining clear, specific, and objective diagnostic criteria. Identifying biomarkers of depressive disorder offers a broad field for researching many regulatory systems of the body. The laboratory markers identified so far are involved in neurotrophic, neuroendocrine, neurotransmitter, metabolic, and inflammatory processes. This review discusses the use of various biomarkers for studying depression, focusing on the most promising ones.

Discovery of Multiple Effects of Reactive Oxygen Species on Lung Adenocarcinoma at the Single-cell and Bulk Tissue Levels.

Reactive oxygen species (ROS) are potential targets for treating malignant tumors. The aim of this study was to probe into the mechanisms of disease development and treatment in lung adenocarcinoma (LUAD). This study investigated the impact of ROS on the progression of LUAD at different transcriptomic levels and analyzed key molecules involved in the regulation of LUAD. Single-cell RNA-seq (scRNA-seq) data of LUAD were clustered and annotated to determine cell types. Scissor cells based on LUAD bulk transcriptome and epithelial scRNA-seq data were used to classify subsets associated with ROS phenotypes. Least absolute shrinkage and selection operator (LASSO) and stepwise multivariate regression analyses were performed between the Scissor-positive and Scissor-negative epithelial cells to select key differentially expressed genes (DEGs) for developing a ROS-related signature. The ROS score was significantly negatively correlated with the overall survival (OS) of LUAD. Seven cell types from the LUAD tissues were identified. The ROS-related gene signature was significantly correlated with metabolism, tumor microenvironment (TME) indicators, and the half-maximal inhibitory concentration (IC50) values of 10 drugs. The gene signature was verified as an independent indicator for LUAD prognosis. The current study provided novel insights into the impact of ROS on LUAD pathology at both single-cell and bulk-tissue levels, facilitating the prognostic evaluation and drug therapy development for patients with LUAD.

CXCL8 and its cognate receptors CXCR1/CXCR2 in primary myelofibrosis.

BCR::ABL1 negative myeloproliferative neoplasms (MPNs) form a distinct group of hematologic malignancies characterized by sustained proliferation of cells from multiple myeloid lineages. With a median survival of 16-35 months in patients with high-risk disease, primary myelofibrosis (PMF) is considered the most aggressive entity amongst all BCR::ABL1 MPNs. Additionally, a significant subset of patients evolves into secondary acute myeloid leukemia (AML) which has an even poorer prognosis compared to de novo AML. As the exact mechanisms of disease development and progression remain to be elucidated, current therapeutic approaches fail to prevent disease progression or transformation into secondary AML. As each MPN entity is characterized by sustained activation of various immune cells and raised cytokine concentrations within bone marrow and peripheral blood, MPNs may be considered as typical inflammation-related malignancies. However, the exact role and consequences of increased cytokine concentrations within bone marrow and peripheral blood plasma are currently incompletely established. Upregulated cytokines can stimulate cellular proliferation or contribute to the development of an inflammation-related bone marrow niche resulting in genotoxicity and thereby supporting mutagenesis. The neutrophil chemoattractant CXCL8 is of specific interest as its concentration is increased within peripheral blood and bone marrow plasma of patients with PMF. Increased concentration of CXCL8 negatively correlates with overall survival. Furthermore, blockage of the CXCR1/2 axis appears to be able to reduce bone marrow fibrosis and megakaryocyte dysmorphia in murine models. Within this review, we summarize available evidence on the role of the CXCL8-CXCR1/2 axis within the pathogenesis of PMF and discuss potential therapeutic modalities targeting either CXCL8 or its cognate receptors CXCR1/2.

Single Sample Molecular Chronology.

ConspectusThis Account presents a new discipline, single sample molecular chronology (SSMC), which studies the relative age of an individual compound occurring in several temporal pools of a single sample in complex media. Geochemists have analytically observed for a long time that several pools of the same compound, e.g., a hydrocarbon or a pesticide, can be isolated from the same sample, e.g., a sediment or a soil, to yield a free compound pool obtained by solvent extraction and then a bound compound pool after treatment of the solid residue and further extraction. Yet the study on the significance of these pools has been limited due to the inherent lack of criteria to clearly distinguish the same compound present in various pools, and, as a consequence, the existence of these pools has been criticized as resulting from a default of extraction during analytical fractionation. Our breakthrough was to distinguish isotopically several temporal pools of a plant-derived C31 n-alkane in a soil sample containing naturally 13C-labeled carbon and then to set up a method, 13C-relative dating, to calculate the relative age of these temporal pools. We observed wide differences in the relative age of the C31 n-alkane in temporal pools of a single soil sample, ranging from -6.7 years for a soil humin-bound homologue to +25.1 years for the free homologue in the coarser soil particle-size fraction. Individual compounds can thus be used as molecular clocks to determine the relative age of temporal pools from the same sample. Moreover, our findings represented the first unambiguous proof that bound compounds are cycling slower and are somehow protected in a complex organo-mineral matrix, key information for the mechanism of carbon sequestration. SSMC could be developed in all disciplines of physical, biological, and environmental sciences manipulating complex media, to study the history of individual compounds. This chronochemistry should provide new information about the origin and transformation of individual compounds in biogeochemical systems. For example, historical information on drugs or pollutants encapsulated in temporal pools of a living organism would bring about critical new knowledge about the mechanisms of disease development. Investigations require isotope tracing using any isotope in natural or artificial abundance. Methods to separate temporal pools are suggested.

DNA-based diagnostics of hereditary diseases of the respiratory tract

The diagnosis of orphan lung diseases often requires specific tests, and treatment is difficult due to problems in understanding the mechanisms of disease development and low incidence. When a therapy is developed, it is very expensive.The aim of the article was to present modern approaches for the genetic diagnosis of hereditary respiratory diseases.Conclusion. A physician of any specialty can encounter an orphan disease in clinical practice. The emergence of new methods for the maintenance and targeted therapy of orphan lung diseases necessitates allertness of both pediatric and adult pulmonologists. Competent management of such patients requires knowledge of the basics of genetics and the modern possibilities of DNA diagnostics, as well as close interdisciplinary cooperation between physicians of different specialties and laboratories.

Alveolar Organoids in Lung Disease Modeling.

Lung organoids display a tissue-specific functional phenomenon and mimic the features of the original organ. They can reflect the properties of the cells, such as morphology, polarity, proliferation rate, gene expression, and genomic profile. Alveolar type 2 (AT2) cells have a stem cell potential in the adult lung. They produce and secrete pulmonary surfactant and proliferate to restore the epithelium after damage. Therefore, AT2 cells are used to generate alveolar organoids and can recapitulate distal lung structures. Also, AT2 cells in human-induced pluripotent stem cell (iPSC)-derived alveolospheres express surfactant proteins and other factors, indicating their application as suitable models for studying cell-cell interactions. Recently, they have been utilized to define mechanisms of disease development, such as COVID-19, lung cancer, idiopathic pulmonary fibrosis, and chronic obstructive pulmonary disease. In this review, we show lung organoid applications in various pulmonary diseases, drug screening, and personalized medicine. In addition, stem cell-based therapeutics and approaches relevant to lung repair were highlighted. We also described the signaling pathways and epigenetic regulation of lung regeneration. It is critical to identify novel regulators of alveolar organoid generations to promote lung repair in pulmonary diseases.

Exfoliation syndrome and exfoliation glaucoma ‐ Current research and Management in Georgia

Exfoliation Syndrome (XFS) is an age‐related disorder of extracellular matrix affecting millions of people worldwide. It is the most common identifiable cause of glaucoma which is characterized by much more severe clinical course, more fluctuation of intraocular pressure (IOP), less response to medical treatment, faster progression of optic nerve atrophy and visual field deterioration, more frequent need of surgical treatment.XFS is a heritable condition. This fact is long known from familial aggregation studies. Very little is known about the mechanisms of disease development. This is especially true about Exfoliation Glaucoma (XFG), considering that not every XFS patient converts to XFG.The only evidence‐based treatment of XFG nowadays is IOP lowering, although addressing mechanisms of IOP elevation could be the best preventive and treatment measure.The aim of this talk is to summarize the current status of genetic studies of XFS/XFG and to provide some tips for treatment based on several clinical examples.

Risk factors, diagnostics and treatment of corneal melting after cataract phacoemulsification

Inflammatory complications of cataract phacoemulsification are among the most urgent and potentially vision-threatening conditions. Corneal melting is a rare but clinically significant condition preceding corneal perforation. The main risk factors are the use of nonsteroidal anti-inflammatory drugs (NSAIDs), severe dry eye disease and rheumatic diseases. The paper presents a literature review and offers an analysis of a clinical case of corneal melting after cataract phacoemulsification in a female patient with severe dry eye disease, which was undiagnosed before surgery. The follow-up period was 5 years. The possibilities and limitations of multiple methods of corneal melting treatment at the stages of persistent epithelial defect and corneal ulcer are discussed. The mechanism of disease development and its link with the pathogenesis of dry eye disease and the role of topical NSAIDs as a trigger for the initiation and progression of corneal melting are considered.

A Synopsis of the Evidence for the Science and Clinical Management of Cardiovascular-Kidney-Metabolic (CKM) Syndrome: A Scientific Statement From the American Heart Association.

A growing appreciation of the pathophysiological interrelatedness of metabolic risk factors such as obesity and diabetes, chronic kidney disease, and cardiovascular disease has led to the conceptualization of cardiovascular-kidney-metabolic syndrome. The confluence of metabolic risk factors and chronic kidney disease within cardiovascular-kidney-metabolic syndrome is strongly linked to risk for adverse cardiovascular and kidney outcomes. In addition, there are unique management considerations for individuals with established cardiovascular disease and coexisting metabolic risk factors, chronic kidney disease, or both. An extensive body of literature supports our scientific understanding of, and approach to, prevention and management for individuals with cardiovascular-kidney-metabolic syndrome. However, there are critical gaps in knowledge related to cardiovascular-kidney-metabolic syndrome in terms of mechanisms of disease development, heterogeneity within clinical phenotypes, interplay between social determinants of health and biological risk factors, and accurate assessments of disease incidence in the context of competing risks. There are also key limitations in the data supporting the clinical care for cardiovascular-kidney-metabolic syndrome, particularly in terms of early-life prevention, screening for risk factors, interdisciplinary care models, optimal strategies for supporting lifestyle modification and weight loss, targeting of emerging cardioprotective and kidney-protective therapies, management of patients with both cardiovascular disease and chronic kidney disease, and the impact of systematically assessing and addressing social determinants of health. This scientific statement uses a crosswalk of major guidelines, in addition to a review of the scientific literature, to summarize the evidence and fundamental gaps related to the science, screening, prevention, and management of cardiovascular-kidney-metabolic syndrome.

HGECDA: A Heterogeneous Graph Embedding Model for CircRNA-Disease Association Prediction.

Circular RNAs (circRNAs) are specifically and abnormally expressed in disease tissues, and thus can be used as biomarkers to diagnose relevant diseases. Predicting circRNA-disease associations will provide essential clues to reveal molecular mechanisms of disease development and discover novel therapeutic targets. Existing algorithms ignore the heterogeneous biological association information related to microRNAs (miRNAs). Based on a heterogeneous graph embedding model, a novel circRNA-disease association prediction method called HGECDA is developed in this paper. The heterogeneous graph network containing circRNA-miRNA-disease association information is first constructed. To sample the heterogeneous information, the meta-path-based random walk that can capture the relevance between various types of nodes is employed. Then, the path embedding model based on skip-gram and random negative sampling is built to acquire the initial feature vectors of circRNAs and diseases. Finally, the CosMulformer model with linearized self-attention and Hadamard product is designed to obtain the circRNA-disease interaction vectors and conduct the prediction task. Experimental results demonstrate the critical role of miRNA in enriching the information of the feature space, the effectiveness of the CosMulformer model in picking out deep local interaction features, and the feasibility of the Hadamard product chosen as the integration pattern in the CosMulformer model. Compared with existing state-of-the-art methods on the same dataset, HGECDA performs better than the other seven algorithms. Moreover, the case studies about breast cancer and colorectal cancer demonstrate the practical value of HGECDA in predicting potential circRNA-disease associations.

Construction of a fluorescence sensing platform based on RISC and CRISPR/Cas12a for the assay of Ago2 enzyme activity

PurposeArgonaute 2 (Ago2) is a protein with nucleic acid endonuclease activity and is ubiquitous in eukaryotic cells. Ago2 is a core member of RNA interference and is involved in important gene regulation in the body and the development of multiple tumors by affecting oncogenic or oncogenic gene expression. Ago2 is a potential tumor biomarker. Therefore, the assay of Ago2 activity can help monitor the disease progression and prognosis and contribute to the study of the mechanism of disease development. MethodsAgo2-based nucleic acid endonuclease activity cleaves the target hairpin nucleic acid chain and progressively stimulates the hybridization chain reaction (HCR) in the sensing strategy, causing signal amplification to form specific dsDNA, which then triggers the powerful non-selective single nucleic acid chain cleavage activity of the CRISPR/cas12a system and releases the fluorescence signal in the reporter probe. ResultsThe sensitive assay of Ago2 enzyme activity was achieved using the biofunctional properties of RNA-induced silencing complex (RISC) and CRISPR/Cas12a. Under the optimized conditions, the fluorescence signal intensity of the assay was positively correlated with the activity concentration of Ago2, with an excellent linear response range of 0.02–20 nM and a limit of detection (LOD) of 10 pM. When applied to the assay of Ago2 in cell lysates, the experimental recovery was 93.33%-107.08%, and the sensing platform was able to detect the Ago2 content in the presence of interference specifically. ConclusionTherefore, the fluorescence sensing platform successfully constructed in this paper is suitable for the assay of endogenous Ago2 activity in complex samples, and the assay method has the advantages of high specificity, sensitive detection, easy operation and low instrumentation requirements, which is expected to be applied to the actual sample assay in clinical settings. Meanwhile, it provides an assay direction for the biofunctional analysis of nucleases and a feasible direction for applying RISC and Crispr/Cas12a in sensing analysis.

Plasma exchange in neurology patients-experience from single center in Montenegro.

Plasma exchange (PE) is widely used in many immune-based neurological diseases. Our aim is to analyze characteristics of PE in neurological patients at the Clinical Center of Montenegro. Our study involved neurological patients treated with PE between January 2020 and April 2022. In total, 246 PEs were performed in 43 patients. We divided patients into 4 groups according to indications. In 8/9 multiple sclerosis (MS) patients a decrease of Expanded Dysability Status Scale at least 0.5 was verified. In 14/20 Guillain Barre syndrome patients reduction of Hughes was observed. Four patients with myasthenia gravis (MG) were treated with PE. The most heterogeneous group (4) consisted of patients in whom the mechanism of disease development is assumed to be immune system dysregulation. Fourteen patients had any adverse event. Our results show that PE is widely used and safe in the treatment of neurological diseases.

Management of alcoholic hepatitis: A clinical perspective.

Alcohol-associated liver disease is the primary cause of liver-related mortality worldwide and one of the most common indications for liver transplantation. Alcoholic hepatitis represents the most acute and severe manifestation of alcohol-associated liver disease and is characterized by a rapid onset of jaundice with progressive inflammatory liver injury, worsening of portal hypertension, and an increased risk for multiorgan failure in patients with excessive alcohol consumption. Severe alcoholic hepatitis is associated with a poor prognosis and high short-term mortality. During the COVID-19 pandemic, rates of alcohol-associated hepatitis have increased significantly, underscoring that it is a serious and growing health problem. However, adequate management of alcohol-associated hepatitis and its complications in everyday clinical practice remains a major challenge. Currently, pharmacotherapy is limited to corticosteroids, although these have only a moderate effect on reducing short-term mortality. In recent years, translational studies deciphering key mechanisms of disease development and progression have led to important advances in the understanding of the pathogenesis of alcoholic hepatitis. Emerging pathophysiology-based therapeutic approaches include anti-inflammatory agents, modifications of the gut-liver axis and intestinal dysbiosis, epigenetic modulation, antioxidants, and drugs targeting liver regeneration. Concurrently, evidence is increasing that early liver transplantation is a safe treatment option with important survival benefits in selected patients with severe alcoholic hepatitis not responding to medical treatment. This narrative review describes current pathophysiology and management concepts of alcoholic hepatitis, provides an update on emerging treatment options, and focuses on the need for holistic and patient-centred treatment approaches to improve prognosis.

Establishment and characterization of CSCRi006-A: an induced pluripotent stem cell line generated from a patient with Diamond-Blackfan Anemia (DBA) carrying ribosomal protein S19 (RPS19) mutation.

Diamond-Blackfan anemia (DBA) is a congenital hypoplastic anemia characterized by ineffective erythropoiesis. DBA is majorly caused by mutations in the ribosomal protein (RP) genes (Gadhiya and Wills in Diamond-Blackfan Anemia, https://www.statpearls.com/ ; 2023). A suitable disease model that yields a continuous supply of erythroid cells is required to study disease pathogenesis and drug discovery. Toward this, we reprogrammed dermal fibroblasts from a DBA patient with a heterozygous mutation c.22-23delAG in the RPS19 gene identified through exome sequencing. To generate induced pluripotent stem cells (iPSCs), we induced episomal expression of the reprogramming factors OTC3/4, L-MYC, LIN28, SOX2, and KLF4, and a p53 shRNA2. The DBA-iPSC line CSCRi006-A generated during this study was extensively characterized for its pluripotency and genome stability. The clone retained normal karyotype and showed high expression levels of pluripotency markers, OCT4, NANOG, SOX2, TRA-I-60, TRA-I-81, and SSEA4. It could differentiate into cells originating from all three germ cell layers, as identified by immunostaining for SOX17 (endoderm), Brachyury (mesoderm), and PAX6 (ectoderm). IPSCs provide a renewable source of cells for in vitro disease modeling. CSCRi006-A, a thoroughly characterized iPSC line carrying heterozygous RPS19 c.22-23delAG mutation, is a valuable cell line for the disease modeling of DBA. This iPSC line can be differentiated into different blood cell types to study the mechanisms of disease development and identify potential treatments.

GeNetOntology: identifying affected gene ontology terms via grouping, scoring, and modeling of gene expression data utilizing biological knowledge-based machine learning.

Introduction: Identifying significant sets of genes that are up/downregulated under specific conditions is vital to understand disease development mechanisms at the molecular level. Along this line, in order to analyze transcriptomic data, several computational feature selection (i.e., gene selection) methods have been proposed. On the other hand, uncovering the core functions of the selected genes provides a deep understanding of diseases. In order to address this problem, biological domain knowledge-based feature selection methods have been proposed. Unlike computational gene selection approaches, these domain knowledge-based methods take the underlying biology into account and integrate knowledge from external biological resources. Gene Ontology (GO) is one such biological resource that provides ontology terms for defining the molecular function, cellular component, and biological process of the gene product. Methods: In this study, we developed a tool named GeNetOntology which performs GO-based feature selection for gene expression data analysis. In the proposed approach, the process of Grouping, Scoring, and Modeling (G-S-M) is used to identify significant GO terms. GO information has been used as the grouping information, which has been embedded into a machine learning (ML) algorithm to select informative ontology terms. The genes annotated with the selected ontology terms have been used in the training part to carry out the classification task of the ML model. The output is an important set of ontologies for the two-class classification task applied to gene expression data for a given phenotype. Results: Our approach has been tested on 11 different gene expression datasets, and the results showed that GeNetOntology successfully identified important disease-related ontology terms to be used in the classification model. Discussion: GeNetOntology will assist geneticists and scientists to identify a range of disease-related genes and ontologies in transcriptomic data analysis, and it will also help doctors design diagnosis platforms and improve patient treatment plans.