3,364 research outputs found
Prediction of Drug-Target Interactions and Drug Repositioning via Network-Based Inference
Drug-target interaction (DTI) is the basis of drug discovery and design. It is time consuming and costly to determine DTI experimentally. Hence, it is necessary to develop computational methods for the prediction of potential DTI. Based on complex network theory, three supervised inference methods were developed here to predict DTI and used for drug repositioning, namely drug-based similarity inference (DBSI), target-based similarity inference (TBSI) and network-based inference (NBI). Among them, NBI performed best on four benchmark data sets. Then a drug-target network was created with NBI based on 12,483 FDA-approved and experimental drug-target binary links, and some new DTIs were further predicted. In vitro assays confirmed that five old drugs, namely montelukast, diclofenac, simvastatin, ketoconazole, and itraconazole, showed polypharmacological features on estrogen receptors or dipeptidyl peptidase-IV with half maximal inhibitory or effective concentration ranged from 0.2 to 10 µM. Moreover, simvastatin and ketoconazole showed potent antiproliferative activities on human MDA-MB-231 breast cancer cell line in MTT assays. The results indicated that these methods could be powerful tools in prediction of DTIs and drug repositioning
Representation learning of drug and disease terms for drug repositioning
Drug repositioning (DR) refers to identification of novel indications for the
approved drugs. The requirement of huge investment of time as well as money and
risk of failure in clinical trials have led to surge in interest in drug
repositioning. DR exploits two major aspects associated with drugs and
diseases: existence of similarity among drugs and among diseases due to their
shared involved genes or pathways or common biological effects. Existing
methods of identifying drug-disease association majorly rely on the information
available in the structured databases only. On the other hand, abundant
information available in form of free texts in biomedical research articles are
not being fully exploited. Word-embedding or obtaining vector representation of
words from a large corpora of free texts using neural network methods have been
shown to give significant performance for several natural language processing
tasks. In this work we propose a novel way of representation learning to obtain
features of drugs and diseases by combining complementary information available
in unstructured texts and structured datasets. Next we use matrix completion
approach on these feature vectors to learn projection matrix between drug and
disease vector spaces. The proposed method has shown competitive performance
with state-of-the-art methods. Further, the case studies on Alzheimer's and
Hypertension diseases have shown that the predicted associations are matching
with the existing knowledge.Comment: Accepted to appear in 3rd IEEE International Conference on
Cybernetics (Spl Session: Deep Learning for Prediction and Estimation
DHLP 1&2: Giraph based distributed label propagation algorithms on heterogeneous drug-related networks
Background and Objective: Heterogeneous complex networks are large graphs
consisting of different types of nodes and edges. The knowledge extraction from
these networks is complicated. Moreover, the scale of these networks is
steadily increasing. Thus, scalable methods are required. Methods: In this
paper, two distributed label propagation algorithms for heterogeneous networks,
namely DHLP-1 and DHLP-2 have been introduced. Biological networks are one type
of the heterogeneous complex networks. As a case study, we have measured the
efficiency of our proposed DHLP-1 and DHLP-2 algorithms on a biological network
consisting of drugs, diseases, and targets. The subject we have studied in this
network is drug repositioning but our algorithms can be used as general methods
for heterogeneous networks other than the biological network. Results: We
compared the proposed algorithms with similar non-distributed versions of them
namely MINProp and Heter-LP. The experiments revealed the good performance of
the algorithms in terms of running time and accuracy.Comment: Source code available for Apache Giraph on Hadoo
A multilayer network approach for guiding drug repositioning in neglected diseases
Drug development for neglected diseases has been historically hampered due to lack of market incentives. The advent of public domain resources containing chemical information from high throughput screenings is changing the landscape of drug discovery for these diseases. In this work we took advantage of data from extensively studied organisms like human, mouse, E. coli and yeast, among others, to develop a novel integrative network model to prioritize and identify candidate drug targets in neglected pathogen proteomes, and bioactive drug-like molecules. We modeled genomic (proteins) and chemical (bioactive compounds) data as a multilayer weighted network graph that takes advantage of bioactivity data across 221 species, chemical similarities between 1.7 105 compounds and several functional relations among 1.67 105 proteins. These relations comprised orthology, sharing of protein domains, and shared participation in defined biochemical pathways. We showcase the application of this network graph to the problem of prioritization of new candidate targets, based on the information available in the graph for known compound-target associations. We validated this strategy by performing a cross validation procedure for known mouse and Trypanosoma cruzi targets and showed that our approach outperforms classic alignment-based approaches. Moreover, our model provides additional flexibility as two different network definitions could be considered, finding in both cases qualitatively different but sensible candidate targets. We also showcase the application of the network to suggest targets for orphan compounds that are active against Plasmodium falciparum in high-throughput screens. In this case our approach provided a reduced prioritization list of target proteins for the query molecules and showed the ability to propose new testable hypotheses for each compound. Moreover, we found that some predictions highlighted by our network model were supported by independent experimental validations as found post-facto in the literature.Fil: Berenstein, Ariel José. Fundación Instituto Leloir; Argentina. Universidad de Buenos Aires. Facultad de IngenierÃa. Departamento de FÃsica; ArgentinaFil: Magariños, MarÃa Paula. Consejo Nacional de Investigaciones CientÃficas y Técnicas. Centro CientÃfico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl AlfonsÃn" (sede Chascomús). Universidad Nacional de San MartÃn. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl AlfonsÃn" (sede Chascomús); ArgentinaFil: Chernomoretz, Ariel. Fundación Instituto Leloir; Argentina. Universidad de Buenos Aires. Facultad de IngenierÃa. Departamento de FÃsica; ArgentinaFil: Fernandez Aguero, Maria Jose. Consejo Nacional de Investigaciones CientÃficas y Técnicas. Centro CientÃfico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl AlfonsÃn" (sede Chascomús). Universidad Nacional de San MartÃn. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl AlfonsÃn" (sede Chascomús); Argentin
Network-based drug ranking and repositioning with respect to DrugBank therapeutic categories
Drug repositioning is a challenging computational problem involving the integration of heterogeneous sources of biomolecular data and the design of label ranking algorithms able to exploit the overall topology of the underlying pharmacological network. In this context, we propose a novel semisupervised drug ranking problem: prioritizing drugs in integrated biochemical networks according to specific DrugBank therapeutic categories. Algorithms for drug repositioning usually perform the inference step into an inhomogeneous similarity space induced by the relationships existing between drugs and a second type of entity (e.g., disease, target, ligand set), thus making unfeasible a drug ranking within a homogeneous pharmacological space. To deal with this problem, we designed a general framework based on bipartite network projections by which homogeneous pharmacological networks can be constructed and integrated from heterogeneous and complementary sources of chemical, biomolecular and clinical information. Moreover, we present a novel algorithmic scheme based on kernelized score functions that adopts both local and global learning strategies to effectively rank drugs in the integrated pharmacological space using different network combination methods. Detailed experiments with more than 80 DrugBank therapeutic categories involving about 1,300 FDA-approved drugs show the effectiveness of the proposed approach
Herb Target Prediction Based on Representation Learning of Symptom related Heterogeneous Network.
Traditional Chinese Medicine (TCM) has received increasing attention as a complementary approach or alternative to modern medicine. However, experimental methods for identifying novel targets of TCM herbs heavily relied on the current available herb-compound-target relationships. In this work, we present an Herb-Target Interaction Network (HTINet) approach, a novel network integration pipeline for herb-target prediction mainly relying on the symptom related associations. HTINet focuses on capturing the low-dimensional feature vectors for both herbs and proteins by network embedding, which incorporate the topological properties of nodes across multi-layered heterogeneous network, and then performs supervised learning based on these low-dimensional feature representations. HTINet obtains performance improvement over a well-established random walk based herb-target prediction method. Furthermore, we have manually validated several predicted herb-target interactions from independent literatures. These results indicate that HTINet can be used to integrate heterogeneous information to predict novel herb-target interactions
Drug repurposing using biological networks
Drug repositioning is a strategy to identify new uses for existing, approved, or research drugs that are outside the scope of its original medical indication. Drug repurposing is based on the fact that one drug can act on multiple targets or that two diseases can have molecular similarities, among others. Currently, thanks to the rapid advancement of high-performance technologies, a massive amount of biological and biomedical data is being generated. This allows the use of computational methods and models based on biological networks to develop new possibilities for drug repurposing. Therefore, here, we provide an in-depth review of the main applications of drug repositioning that have been carried out using biological network models. The goal of this review is to show the usefulness of these computational methods to predict associations and to find candidate drugs for repositioning in new indications of certain diseases
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