Systems biology-derived genetic signatures of mastitis in dairy cattle : a new avenue for drug repurposing

Mastitis, a disease with high incidence worldwide, is the most prevalent and costly disease in the dairy industry. Gram-negative bacteria such as Escherichia coli (E. coli) are assumed to be among the leading agents causing acute severe infection with clinical signs. E. Coli, environmental mastitis pathogens, are the primary etiological agents of bovine mastitis in well-managed dairy farms. Response to E. Coli infection has a complex pattern affected by genetic and environmental parameters. On the other hand, the efficacy of antibiotics and/or anti-inflammatory treatment in E. coli mastitis is still a topic of scientific debate, and studies on the treatment of clinical cases show conflicting results. Unraveling the bio-signature of mastitis in dairy cattle can open new avenues for drug repurposing. In the current research, a novel, semi-supervised heterogeneous label propagation algorithm named Heter-LP, which applies both local and global network features for data integration, was used to potentially identify novel therapeutic avenues for the treatment of E. coli mastitis. Online data repositories relevant to known diseases, drugs, and gene targets, along with other specialized biological information for E. coli mastitis, including critical genes with robust bio-signatures, drugs, and related disorders, were used as input data for analysis with the Heter-LP algorithm. Our research identified novel drugs such as Glibenclamide, Ipratropium, Salbutamol, and Carbidopa as possible therapeutics that could be used against E. coli mastitis. Predicted relationships can be used by pharmaceutical scientists or veterinarians to find commercially efficacious medicines or a combination of two or more active compounds to treat this infectious disease

Novelty detection with self-organizing maps for autonomous extraction of salient tracking features

International audienceIn the image processing field, many tracking algorithms rely on prior knowledge like color, shape or even need a database of the objects to be tracked. This may be a problem for some real world applications that cannot fill those prerequisite. Based on image compression techniques, we propose to use Self-Organizing Maps to robustly detect novelty in the input video stream and to produce a saliency map which will outline unusual objects in the visual environment. This saliency map is then processed by a Dynamic Neural Field to extract a robust and continuous tracking of the position of the object. Our approach is solely based on unsupervised neural networks and does not need any prior knowledge, therefore it has a high adaptability to different inputs and a strong robustness to noisy environments

Heter-LP: A Heterogeneous Label Propagation Method for Drug Repositioning

Using existing drugs for diseases which are not developed for their treating (drug repositioning) provides a new approach to developing drugs at a lower cost, faster, and more secured. We proposed a method for drug repositioning which can predict simple and complex relationships between drugs, drug targets, and diseases. Since biological networks typically present a suitable model for relationships between different biological concepts, our primary approach is to analyze graphs and complex networks in the study of drugs and their therapeutic effects. Given the nature of existing data, the use of semi-supervised learning methods is crucial. So, in our research, we have developed a label propagation method to predict drug-target, drug-disease, and disease-target interactions (Heter-LP), which integrates various data sources at different levels. The predicted interactions are the most prominent relationships among the millions of relationships suggested to the related researchers for further investigation. The main advantages of Heter-LP are the effective integration of input data, eliminating the need for negative samples, and the use of local and global features together. The main steps of this research are as follows. The first step is the construction of a heterogeneous network as a data modeling task, in which data are collected and prepared. The second step is predicting potential interactions. We present a new label propagation algorithm for heterogeneous networks, which consists of two parts, one mapping and the other an iterative method for determining the final labels of the entire network vertices. Finally, for evaluation, we calculated the AUC and AUPR with tenfold cross-validation and compared the results with the best available methods for label propagation in heterogeneous networks and drug repositioning. Also, a series of experimental evaluations and some specific case studies have been presented. The result of the AUC and AUPR for Heter-LP was much higher than the average of the best available methods

Systems Biology–Derived Genetic Signatures of Mastitis in Dairy Cattle: A New Avenue for Drug Repurposing

Mastitis, a disease with high incidence worldwide, is the most prevalent and costly disease in the dairy industry. Gram-negative bacteria such as Escherichia coli (E. coli) are assumed to be among the leading agents causing acute severe infection with clinical signs. E. Coli, environmental mastitis pathogens, are the primary etiological agents of bovine mastitis in well-managed dairy farms. Response to E. Coli infection has a complex pattern affected by genetic and environmental parameters. On the other hand, the efficacy of antibiotics and/or anti-inflammatory treatment in E. coli mastitis is still a topic of scientific debate, and studies on the treatment of clinical cases show conflicting results. Unraveling the bio-signature of mastitis in dairy cattle can open new avenues for drug repurposing. In the current research, a novel, semi-supervised heterogeneous label propagation algorithm named Heter-LP, which applies both local and global network features for data integration, was used to potentially identify novel therapeutic avenues for the treatment of E. coli mastitis. Online data repositories relevant to known diseases, drugs, and gene targets, along with other specialized biological information for E. coli mastitis, including critical genes with robust bio-signatures, drugs, and related disorders, were used as input data for analysis with the Heter-LP algorithm. Our research identified novel drugs such as Glibenclamide, Ipratropium, Salbutamol, and Carbidopa as possible therapeutics that could be used against E. coli mastitis. Predicted relationships can be used by pharmaceutical scientists or veterinarians to find commercially efficacious medicines or a combination of two or more active compounds to treat this infectious diseaseThis article is published as Sharifi S, Lotfi Shahreza M, Pakdel A, Reecy JM, Ghadiri N, Atashi H, Motamedi M, Ebrahimie E. Systems Biology–Derived Genetic Signatures of Mastitis in Dairy Cattle: A New Avenue for Drug Repurposing. Animals. 2022; 12(1):29. https://doi.org/10.3390/ani12010029. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)

Heter-LP: A heterogeneous label propagation algorithm and its application in drug repositioning

Drug repositioning offers an effective solution to drug discovery, saving both time and resources by finding new indications for existing drugs. Typically, a drug takes effect via its protein targets in the cell. As a result, it is necessary for drug development studies to conduct an investigation into the interrelationships of drugs, protein targets, and diseases. Although previous studies have made a strong case for the effectiveness of integrative network-based methods for predicting these interrelationships, little progress has been achieved in this regard within drug repositioning research. Moreover, the interactions of new drugs and targets (lacking any known targets and drugs, respectively) cannot be accurately predicted by most established methods. In this paper, we propose a novel semi-supervised heterogeneous label propagation algorithm named Heter-LP, which applies both local and global network features for data integration. To predict drug-target, disease-target, and drug-disease associations, we use information about drugs, diseases, and targets as collected from multiple sources at different levels. Our algorithm integrates these various types of data into a heterogeneous network and implements a label propagation algorithm to find new interactions. Statistical analyses of 10-fold cross-validation results and experimental analyses support the effectiveness o