A model depicts the relationship between clinical phenotypes and genotypes on a set of genetic polymorphisms. After the model is constructed and validated, it may be used to predict clinical phenotypes such as traits of complex diseases. A pharmacogenomic model is used to predict the efficacies or adverse drug reactions of a medication. The construction of a model is a challenging task. This is because a single-locus polymorphism does not contain enough information to stratify patients in general, given the complex biological mechanisms involved. An exhaustive search for the correct combination of genotypes across multiple loci is, however, computationally infeasible. We are, thus, motivated to propose a novel algorithm for the construction of models using the multiple single-nucleotide polymorphism (SNP) information in diplotype forms. This algorithm utilizes the techniques of genetic algorithms and Boolean algebra (GABA). The proposed algorithm is tested on simulated data, as well as real genotype datasets of chronic hepatitis C patients treated with interferon-combined therapy. A model for predicting the treatment efficacy is constructed and validated. The results showed that the proposed algorithm is very effective in deriving models comprising multiple SNPs.
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http://dx.doi.org/10.1007/s10038-006-0016-2 | DOI Listing |
Circ Heart Fail
January 2025
Aswan Heart Center, Magdi Yacoub Heart Foundation, Egypt (A.M.I., M.R., A. Elsawy, M.H., S.H., W.E., A. Elaithy, A. Elguindy, A. Afifi, Y.A., M.Y.).
Background: Changes in the phenotype and genotype in hypertrophic cardiomyopathy (HCM) are thought to involve the myocardium as well as extracardiac tissues. Here, we describe the structural and functional changes in the ascending aorta of obstructive patients with HCM.
Methods: Changes in the aortic wall were studied in a cohort of 101 consecutive patients with HCM undergoing myectomy and 9 normal controls.
Arterioscler Thromb Vasc Biol
January 2025
Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Germany.
Background: Clinical expressivity of the thrombophilic factor V Leiden (FVL) mutation is highly variable. Recently, we demonstrated an increased APC (activated protein C) response in asymptomatic FVL carriers compared with FVL carriers with a history of venous thromboembolism (VTE) after in vivo coagulation activation. Here, we further explored this association using a recently developed ex vivo model based on patient-specific endothelial colony-forming cells (ECFCs).
View Article and Find Full Text PDFFront Vet Sci
January 2025
Centre of Experimental and Clinical Regenerative Medicine, Small Animal Clinic, University of Veterinary Medicine and Pharmacy in Košice, Košice, Slovakia.
Eggshell membrane (ESM) is a rich source of bioactive compounds, including proteins, peptides, and antioxidants, contributing to its potential therapeutic benefits. These natural antioxidants might help neutralize reactive oxygen species (ROS) and modulate inflammatory responses, which are often linked with chondrocyte damage in osteoarthritis. In this study, we investigated the functional effects of ESM proteins on HO-induced oxidative stress in a neonatal canine chondrocytes.
View Article and Find Full Text PDFFront Immunol
January 2025
Department of Medical Immunology, Medical University of Gdansk, Gdansk, Poland.
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease, characterized by impaired wound repair, tissue remodeling and fibrosis. Immune system may participate in the development and progression of the disease as indicated by altered activity in IPF sufferers. This study investigates the immune response to the BNT162b2 COVID-19 vaccine in patients with IPF compared to healthy controls, with a particular focus on evaluation of antibody responses, interferon-gamma release, cytokine profiling and a broad panel of immune cell subpopulations.
View Article and Find Full Text PDFFront Immunol
January 2025
Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche U1236, Université Rennes, Etablissement Français du Sang Bretagne, LabEx IGO, Rennes, France.
Introduction: Myeloid cells trafficking from the periphery to the central nervous system are key players in multiple sclerosis (MS) through antigen presentation, cytokine secretion and repair processes.
Methods: Combination of mass cytometry on blood cells from 60 MS patients at diagnosis and 29 healthy controls, along with single cell RNA sequencing on paired blood and cerebrospinal fluid (CSF) samples from 5 MS patients were used for myeloid cells detailing.
Results: Myeloid compartment study demonstrated an enrichment of a peculiar classical monocyte population in 22% of MS patients at the time of diagnosis.
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