1,721,023 research outputs found
Reproducibility and Generalization of a Relation Extraction System for Gene-Disease Associations
Full text linkUnderstanding the interactions between
genes and diseases is a great resource for improving patient care as it could provide the founda-
tion for curative therapies, beneficial treatments, and preventative measures
Virus Engineering and Applications
No full textThis Special Issue highlights multiple facets of virus engineering, ranging from the dissection of the biological properties of individual viral functions in the context of safe genomic backbones, virus genetic modification for applications in gene therapy, oncolytic virotherapy and vaccine production, to the hurdles presented by quality control and the delivery of viruses for their final applications and finally to the simulation, prediction and validation of virus evolution [...]
Oncolytic Viruses in the Era of Omics, Computational Technologies, and Modeling: Thesis, Antithesis, and Synthesis
Full text linkOncolytic viruses (OVs) are the frontier therapy for refractory cancers, especially in integration with immunomodulation strategies. In cancer immunovirotherapy, the many available "omics" and systems biology technologies generate at a fast pace a challenging huge amount of data, where apparently clashing information mirrors the complexity of individual clinical situations and OV used. In this review, we present and discuss how currently big data analysis, on one hand and, on the other, simulation, modeling, and computational technologies, provide invaluable support to interpret and integrate "omic" information and drive novel synthetic biology and personalized OV engineering approaches for effective immunovirotherapy. Altogether, these tools, possibly aided in the future by artificial intelligence as well, will allow for the blending of the information into OV recombinants able to achieve tumor clearance in a patient-tailored way. Various endeavors to the envisioned "synthesis" of turning OVs into personalized theranostic agents are presented
Optical biosensor analysis in studying herpes simplex virus glycoprotein D binding to target nectin1 receptor
No full textStudies on molecular interactions between cellular receptors of herpes simplex virus (HSV) and the viral glycoproteins showing receptor-binding activity are of great relevance for understanding the molecular basis of virus entry. Information on such interactions further provides the basis for a rational design of antiviral drugs. A variety of biochemical and biophysical methodologies are used for determining the binding parameters of interacting biomolecules. Most of them require relatively high amounts of the analyzed compounds, or the use of labeled target molecules. Here, we report the study of the binding of two recombinant forms of HSV glycoprotein D, gD(Δ290-299t) and gD(305t), and a recombinant form of the human cellular receptor for HSV, nectin1-Fc, by using an optical biosensor (IAsys Plus, Affinity Sensors, UK). This device detects and quantifies the changes in refractive index in the vicinity of the surface of sensor chips to which ligands are immobilized. The changes in the refractive index are proportional to the change in the absorbed mass, thus the analysis allows the monitoring of the interaction process in real-time and the determination of the binding parameters. HSV cellular receptor has been immobilized on the surface of the biosensor cuvette, bearing a carboxymethyl dextran layer. The immobilized receptor cuvette was then used for the binding experiments of the two glycoproteins. A significant difference in their dissociation constants was determined, showing for the gD(Δ290-299t) protein a much higher affinity (KD, 2.8×10-7 M) with respect to gD(305t) (KD, 2.8×10-6 M). The active ligand concentration decreased on time, however the binding properties of the immobilized receptor were maintained over 5 weeks. © 2003 Elsevier Science B.V. All rights reserved
An Ontology-Driven Knowledge Extraction Tool for Pathology Record Classification
Full text linkThe information in pathology diagnostic reports is often encoded in natural language. Extracting such knowledge can be instrumental in developing clinical decision support systems. However, the digital pathology domain lacks knowledge extraction systems suited to the task. One of the few examples is the Semantic Knowledge Extractor Tool (SKET), a hybrid knowledge extraction system combining a rule-based expert system with pre-trained ML models. SKET has been designed to extract knowledge from colon, cervix, and lung cancer diagnostic reports. To do so, the system employs an ontology-driven approach, where the extracted entities are linked with concepts modeled through a reference ontology, namely, the ExaMode ontology. In this work, we adapt SKET to a newer version of the ExaMode ontology and extend the method to account for an additional use case: Celiac disease. Our experimental results show that: 1) the new version of SKET outperforms the previous one on colon, cervix, and lung canc..
The biology and natural history of two emerging pathogens: Human herpesviruses 6 and 7
No full textHuman herpesvirus 6, the causative agent of exanthem subitum, is emerging as an opportunistic pathogen in the growing population of immunosuppressed individuals, mainly affecting transplant recipients and AIDS patients. Human herpesvirus 6 has been associated with acute episodes of relapsing-remitting multiple sclerosis, with controversial reports from different research groups. Human herpesvirus 7, which is occasionally the causative agent of exanthem subitum, or fever without rash, appears to be of lower pathogenicity, but is also emerging as a possible agent of opportunistic infections. The genomes of both viruses are now fully sequenced and show an overlapping organization. The sequences will provide a basis for our understanding, at the molecular level, of the behaviour of the viruses in humans, and for the development of recombinant diagnostic reagents
Herpes simplex virus oncolytic immunovirotherapy: The blossoming branch of multimodal therapy
Full text linkOncolytic viruses are smart therapeutics against cancer due to their potential to replicate and produce the needed therapeutic dose in the tumor, and to their ability to self-exhaust upon tumor clearance. Oncolytic virotherapy strategies based on the herpes simplex virus are reaching their thirties, and a wide variety of approaches has been envisioned and tested in many different models, and on a range of tumor targets. This huge effort has culminated in the primacy of an oncolytic HSV (oHSV) being the first oncolytic virus to be approved by the FDA and EMA for clinical use, for the treatment of advanced melanoma. The path has just been opened; many more cancer types with poor prognosis await effective and innovative therapies, and oHSVs could provide a promising solution, especially as combination therapies and immunovirotherapies. In this review, we analyze the most recent advances in this field, and try to envision the future ahead of oHSVs
Publishing CoreKB Facts as Nanopublications
No full textThe Collaborative Oriented Relation Extraction (CORE) system generates gene expression-cancer associations by combining scientific evidence from the literature. Such facts are then ingested into the CoreKB platform, where one can browse and search for associations. In this work, we publish 197, 511 assertions from CoreKB as nanopublications, allowing the sharing of machine-readable gene-cancer associations while tracking their provenance and publication information
Bootstrapping Gene Expression-Cancer Knowledge Bases with Limited Human Annotations
Full text linkWe introduce the Collaborative Oriented Relation Extraction (CORE) system for Knowledge Base Construction, based on the combination of Relation Extraction (RE) methods and domain experts feedback. CORE features a seamless, transparent, and modular architecture that suits large-scale processing. Via active learning, the CORE system bootstraps Knowledge Bases (KBs) and then employs RE methods to scale to large text corpora. We employ CORE to build one of the largest KBs focusing on fine-grained gene expression- cancer associations, fundamental to complement and validate experimental data for precision medicine and cancer research. We conducted comprehensive experiments showing the robustness of the approach and highlighting the scalability of CORE to large text corpora with limited manual annotations
The novel receptors that mediate the entry of herpes simplex viruses and animal alphaherpesviruses into cells
No full textAn extended array of cell surface molecules serve as receptors for HSV entry into cells. In addition to the heparan sulphate glycosaminoglycans, which mediate the attachment of virion to cells, HSV requires an entry receptor. The repertoire of entry receptors into human cells includes molecules from three structurally unrelated molecular families. They are (i) HveA (herpesvirus entry mediator A), (ii) members of the nectin family, (iii) 3-O-sulphated heparan sulphate. The molecules have different attributes and play potentially different roles in HSV infection and spread to human tissues. All the human entry receptors interact physically with the virion envelope glycoprotein D (gD). (i) HveA is a member of the TNF-receptor family. It mediates entry of a restricted range of HSV strains. Its expression is restricted to few lineages (e.g. T-lymphocytes). (ii) The human nectin1α (HIgR), nectin1δ (PRR1-HveC), and the nectin2α (PRR2α-HveB) and nectin2δ (PRR2δ) belong to the immunoglobulin superfamily. They are homologues of the poliovirus receptor (CD155), with which they share the overall structure of the ectodomain. The human nectin1α-δ are broadly expressed in cell lines of different lineages, are expressed in human tissue targets of HSV infection, serve as receptors for all HSV-1 and HSV-2 strains tested and mediate entry not only of free virions, but also cell-to-cell spread of virus. (iii) The 3-O-sulphated heparan sulphate is expressed in some selected human cell lines (e.g. endothelial and mast cells) and human tissues, and mediates entry of HSV-1, but not HSV-2. The human nectin2α and nectin2δ serve as receptors for a narrow range of viruses. A characteristic of the human nectin1α-δ is the promiscuous species non-specific receptor activity towards the animal alphaherpesviruses, pseudorabies virus (PrV) and bovine herpesvirus 1 (BHV-1). By contrast with the human nectin1δ, its murine homologue (mNectin1δ) does not bind gD at detectable level, yet it mediates entry of HSV, as well as of PrV and BHV-1. This provides the first example of a mediator of HSV entry independent of a detectable interaction with gD. Copyright (C) 2000 John Wiley and Sons, Ltd
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