RESUMEN
Network biology is a powerful framework for studying the structure, function, and dynamics of biological systems, offering insights into the balance between health and disease states. The field is seeing rapid progress in all of its aspects: data availability, network synthesis, network analytics, and impactful applications in medicine and drug development. We review the most recent and significant results in network biomedicine, with a focus on the latest data, analytics, software resources, and applications in medicine. We also discuss what in our view are the likely directions of impactful development over the next few years.
Asunto(s)
Biología Computacional , Reposicionamiento de Medicamentos , Reposicionamiento de Medicamentos/métodos , Humanos , Biología Computacional/métodos , Programas InformáticosRESUMEN
Control theory has seen recently impactful applications in network science, especially in connections with applications in network medicine. A key topic of research is that of finding minimal external interventions that offer control over the dynamics of a given network, a problem known as network controllability. We propose in this article a new solution for this problem based on genetic algorithms. We tailor our solution for applications in computational drug repurposing, seeking to maximize its use of FDA-approved drug targets in a given disease-specific protein-protein interaction network. We demonstrate our algorithm on several cancer networks and on several random networks with their edges distributed according to the Erdos-Rényi, the Scale-Free, and the Small World properties. Overall, we show that our new algorithm is more efficient in identifying relevant drug targets in a disease network, advancing the computational solutions needed for new therapeutic and drug repurposing approaches.
Asunto(s)
Algoritmos , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Reposicionamiento de Medicamentos/métodos , Proteínas de Neoplasias/genética , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Biología Computacional/métodos , Femenino , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes/efectos de los fármacos , Humanos , Terapia Molecular Dirigida , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/metabolismo , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Medicamentos bajo Prescripción/uso terapéutico , Mapas de Interacción de Proteínas/efectos de los fármacosRESUMEN
MOTIVATION: There is an increasing amount of data coming from genome-wide studies identifying disease-specific survivability-essential proteins and host factors critical to a cell becoming infected. Targeting such proteins has a strong potential for targeted, precision therapies. Typically however, too few of them are drug targetable. An alternative approach is to influence them through drug targetable proteins upstream of them. Structural target network controllability is a suitable solution to this problem. It aims to discover suitable source nodes (e.g. drug targetable proteins) in a directed interaction network that can control (through a suitable set of input functions) a desired set of targets. RESULTS: We introduce NetControl4BioMed, a free open-source web-based application that allows users to generate or upload directed protein-protein interaction networks and to perform target structural network controllability analyses on them. The analyses can be customized to focus the search on drug targetable source nodes, thus providing drug therapeutic suggestions. The application integrates protein data from HGNC, Ensemble, UniProt, NCBI and InnateDB, directed interaction data from InnateDB, Omnipath and SIGNOR, cell-line data from COLT and DepMap, and drug-target data from DrugBank. AVAILABILITYAND IMPLEMENTATION: The application and data are available online at https://netcontrol.combio.org/. The source code is available at https://github.com/Vilksar/NetControl4BioMed under an MIT license.