scholarly journals LPbyCD: a new scalable and interpretable approach for Link Prediction via Community Detection in bipartite networks

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Maksim Koptelov ◽  
Albrecht Zimmermann ◽  
Bruno Crémilleux ◽  
Lina F. Soualmia

AbstractMany aspects from real life with bi-relational structure can be modeled as bipartite networks. This modeling allows the use of some standard solutions for prediction and/or recommendation of new relations between objects in such networks. In this work, we combine an existing bipartite local models method with approaches for link prediction from communities to address the link prediction problem in this type of networks. The motivation of this work stems from the importance of an application task, drug–target interaction prediction. Searching valid drug candidates for a given biological target is an essential part of modern drug development. We model the problem as link prediction in a bipartite multi-layer network, which helps to aggregate different sources of information into one single structure and as a result improves the quality of link prediction. We adapt existing community measures for link prediction to the case of bipartite multi-layer networks, propose alternative ways for exploiting communities, and show experimentally that our approach is competitive with the state-of-the-art. We also demonstrate the scalability of our approach and assess interpretability. Additional evaluations on data of a different origin than drug–target interactions demonstrate the genericness of the proposed approach.

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Maha A. Thafar ◽  
Rawan S. Olayan ◽  
Somayah Albaradei ◽  
Vladimir B. Bajic ◽  
Takashi Gojobori ◽  
...  

AbstractDrug–target interaction (DTI) prediction is a crucial step in drug discovery and repositioning as it reduces experimental validation costs if done right. Thus, developing in-silico methods to predict potential DTI has become a competitive research niche, with one of its main focuses being improving the prediction accuracy. Using machine learning (ML) models for this task, specifically network-based approaches, is effective and has shown great advantages over the other computational methods. However, ML model development involves upstream hand-crafted feature extraction and other processes that impact prediction accuracy. Thus, network-based representation learning techniques that provide automated feature extraction combined with traditional ML classifiers dealing with downstream link prediction tasks may be better-suited paradigms. Here, we present such a method, DTi2Vec, which identifies DTIs using network representation learning and ensemble learning techniques. DTi2Vec constructs the heterogeneous network, and then it automatically generates features for each drug and target using the nodes embedding technique. DTi2Vec demonstrated its ability in drug–target link prediction compared to several state-of-the-art network-based methods, using four benchmark datasets and large-scale data compiled from DrugBank. DTi2Vec showed a statistically significant increase in the prediction performances in terms of AUPR. We verified the "novel" predicted DTIs using several databases and scientific literature. DTi2Vec is a simple yet effective method that provides high DTI prediction performance while being scalable and efficient in computation, translating into a powerful drug repositioning tool.


2019 ◽  
Vol 25 (25) ◽  
pp. 2772-2787 ◽  
Author(s):  
Raghu P. Mailavaram ◽  
Omar H.A. Al-Attraqchi ◽  
Supratik Kar ◽  
Shinjita Ghosh

Adenosine receptors (ARs) belongs to the family of G-protein coupled receptors (GPCR) that are responsible for the modulation of a wide variety of physiological functions. The ARs are also implicated in many diseases such as cancer, arthritis, cardiovascular and renal diseases. The adenosine A3 receptor (A3AR) has emerged as a potential drug target for the progress of new and effective therapeutic agents for the treatment of various pathological conditions. This receptor’s involvement in many diseases and its validity as a target has been established by many studies. Both agonists and antagonists of A3AR have been extensively investigated in the last decade with the goal of developing novel drugs for treating diseases related to immune disorders, inflammation, cancer, and others. In this review, we shall focus on the medicinal chemistry of A3AR ligands, exploring the diverse chemical classes that have been projected as future leading drug candidates. Also, the recent advances in the therapeuetic applications of A3AR ligands are highlighted.


2020 ◽  
Vol 21 (10) ◽  
pp. 1011-1026
Author(s):  
Bruna O. Costa ◽  
Marlon H. Cardoso ◽  
Octávio L. Franco

: Aminoglycosides and β-lactams are the most commonly used antimicrobial agents in clinical practice. This occurs because they are capable of acting in the treatment of acute bacterial infections. However, the effectiveness of antibiotics has been constantly threatened due to bacterial pathogens producing resistance enzymes. Among them, the aminoglycoside-modifying enzymes (AMEs) and β-lactamase enzymes are the most frequently reported resistance mechanisms. AMEs can inactivate aminoglycosides by adding specific chemical molecules in the compound, whereas β-lactamases hydrolyze the β-lactams ring, preventing drug-target interaction. Thus, these enzymes provide a scenario of multidrug-resistance and a significant threat to public health at a global level. In response to this challenge, in recent decades, several studies have focused on the development of inhibitors that can restore aminoglycosides and β-lactams activity. In this context, peptides appear as a promising approach in the field of inhibitors for future antibacterial therapies, as multiresistant bacteria may be susceptible to these molecules. Therefore, this review focused on the most recent findings related to peptide-based inhibitors that act on AMEs and β-lactamases, and how these molecules could be used for future treatment strategies.


2013 ◽  
Vol 13 (14) ◽  
pp. 1636-1649 ◽  
Author(s):  
Esvieta Tenorio-Borroto ◽  
Xerardo Garcia-Mera ◽  
Claudia Penuelas-Rivas ◽  
Juan Vasquez-Chagoyan ◽  
Francisco Prado-Prado ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Pusheng Quan ◽  
Kai Wang ◽  
Shi Yan ◽  
Shirong Wen ◽  
Chengqun Wei ◽  
...  

AbstractThis study aimed to identify potential novel drug candidates and targets for Parkinson’s disease. First, 970 genes that have been reported to be related to PD were collected from five databases, and functional enrichment analysis of these genes was conducted to investigate their potential mechanisms. Then, we collected drugs and related targets from DrugBank, narrowed the list by proximity scores and Inverted Gene Set Enrichment analysis of drug targets, and identified potential drug candidates for PD treatment. Finally, we compared the expression distribution of the candidate drug-target genes between the PD group and the control group in the public dataset with the largest sample size (GSE99039) in Gene Expression Omnibus. Ten drugs with an FDR < 0.1 and their corresponding targets were identified. Some target genes of the ten drugs significantly overlapped with PD-related genes or already known therapeutic targets for PD. Nine differentially expressed drug-target genes with p < 0.05 were screened. This work will facilitate further research into the possible efficacy of new drugs for PD and will provide valuable clues for drug design.


2021 ◽  
Vol 14 (7) ◽  
pp. 692
Author(s):  
Ryldene Marques Duarte da Cruz ◽  
Francisco Jaime Bezerra Mendonça-Junior ◽  
Natália Barbosa de Mélo ◽  
Luciana Scotti ◽  
Rodrigo Santos Aquino de Araújo ◽  
...  

Rheumatoid arthritis, arthrosis and gout, among other chronic inflammatory diseases are public health problems and represent major therapeutic challenges. Non-steroidal anti-inflammatory drugs (NSAIDs) are the most prescribed clinical treatments, despite their severe side effects and their exclusive action in improving symptoms, without effectively promoting the cure. However, recent advances in the fields of pharmacology, medicinal chemistry, and chemoinformatics have provided valuable information and opportunities for development of new anti-inflammatory drug candidates. For drug design and discovery, thiophene derivatives are privileged structures. Thiophene-based compounds, like the commercial drugs Tinoridine and Tiaprofenic acid, are known for their anti-inflammatory properties. The present review provides an update on the role of thiophene-based derivatives in inflammation. Studies on mechanisms of action, interactions with receptors (especially against cyclooxygenase (COX) and lipoxygenase (LOX)), and structure-activity relationships are also presented and discussed. The results demonstrate the importance of thiophene-based compounds as privileged structures for the design and discovery of novel anti-inflammatory agents. The studies reveal important structural characteristics. The presence of carboxylic acids, esters, amines, and amides, as well as methyl and methoxy groups, has been frequently described, and highlights the importance of these groups for anti-inflammatory activity and biological target recognition, especially for inhibition of COX and LOX enzymes.


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