Multiple objectives have emerged in tuning protein-protein interaction (PPI) networks, such as identifying cross-species network similarities and predicting protein complexes and functions. Despite the proliferation of tuning methodologies, challenges remain in balancing accuracy and efficiency. In this paper, we introduce GA2Vec, a novel approach for globally aligning multiple PPI networks using genetic algorithms in a many-to-many fashion. GA2Vec leverages vector embeddings of protein sequences from ProtBERT, ESM-2, and ProtT5-XL-UniRef50 to reconstruct weighted PPI networks, incorporating functional similarity through Gene Ontology (GO) term embeddings derived from the Anc2vec method. We employ four community detection algorithms to generate candidate clusters from the weighted graph, serving as initial solutions for the genetic algorithm. The genetic algorithm optimizes network alignment by refining these clusters using a fitness function based on similarity scores from pre-trained embeddings and GO terms, achieving a robust global network alignment. We demonstrate the effectiveness of our method through experiments on eukaryotic, prokaryotic, SARS-CoV, and virus-host biological networks. It achieves robust alignment between SARS-CoV-2 and SARS-CoV-1 PPI networks, balancing $F1$, cluster interaction quality ($CIQ$), internal cluster quality ($ICQ$), consistent clusters, and $sensitivity$, with scores reflecting its adaptability to diverse biological contexts.

Following the publication of the original article [1], the authors identified errors in calculating the percentages of improvement and deterioration among DTIOG variants in the Results and discussion section. The changes have been highlighted with bold typeface and are shown in Additional file 1. The original article [1] has been corrected.

BACKGROUND: The pharmaceutical field faces a significant challenge in validating drug target interactions (DTIs) due to the time and cost involved, leading to only a fraction being experimentally verified. To expedite drug discovery, accurate computational methods are essential for predicting potential interactions. Recently, machine learning techniques, particularly graph-based methods, have gained prominence. These methods utilize networks of drugs and targets, employing knowledge graph embedding (KGE) to represent structured information from knowledge graphs in a continuous vector space. This phenomenon highlights the growing inclination to utilize graph topologies as a means to improve the precision of predicting DTIs, hence addressing the pressing requirement for effective computational methodologies in the field of drug discovery. RESULTS: The present study presents a novel approach called DTIOG for the prediction of DTIs. The methodology employed in this study involves the utilization of a KGE strategy, together with the incorporation of contextual information obtained from protein sequences. More specifically, the study makes use of Protein Bidirectional Encoder Representations from Transformers (ProtBERT) for this purpose. DTIOG utilizes a two-step process to compute embedding vectors using KGE techniques. Additionally, it employs ProtBERT to determine target-target similarity. Different similarity measures, such as Cosine similarity or Euclidean distance, are utilized in the prediction procedure. In addition to the contextual embedding, the proposed unique approach incorporates local representations obtained from the Simplified Molecular Input Line Entry Specification (SMILES) of drugs and the amino acid sequences of protein targets. CONCLUSIONS: The effectiveness of the proposed approach was assessed through extensive experimentation on datasets pertaining to Enzymes, Ion Channels, and G-protein-coupled Receptors. The remarkable efficacy of DTIOG was showcased through the utilization of diverse similarity measures in order to calculate the similarities between drugs and targets. The combination of these factors, along with the incorporation of various classifiers, enabled the model to outperform existing algorithms in its ability to predict DTIs. The consistent observation of this advantage across all datasets underlines the robustness and accuracy of DTIOG in the domain of DTIs. Additionally, our case study suggests that the DTIOG can serve as a valuable tool for discovering new DTIs.

Breast-cancer (BC) is the most common invasive cancer in women, with considerable death. Given that, BC is classified as a hormone-dependent cancer, when it collides with pregnancy, different questions may arise for which there are still no convincing answers. To deal with this issue, two new frameworks are proposed within this paper: CoRaM and Dist-CoRaM. The former is the first unified framework dedicated to the extraction of a generic basis of Correlated-Rare Association rules from gene expression data. The proposed approach has been successfully applied on a breast-cancer Gene Expression Matrix (GSE1379) with very promising results. The latter, the Dist-CoRaM approach, is a big-data processing based on Apache spark framework, dealing with correlation mining from micro-array pregnancy associated breast-cancer assays (PABC) data. It is successfully applied on the (GSE31192) gene expression matrix (GEM). The correlated patterns of gene-sets shed light on the fact that PABC exhibits heightened aggressiveness compared to cancers for Non-PABC women. Our findings suggest that higher levels of estrogen and progesterone hormones, unfortunately, are very keen to the increase of the tumor aggressiveness and the proliferation of the cancer.

In this work, we address the task of extracting application-specific taxonomies from the category hierarchy of Wikipedia. Previous work on pruning the Wikipedia knowledge graph relied on silver standard taxonomies which can only be automatically extracted for a small subset of domains rooted in relatively focused nodes, placed at an intermediate level in the knowledge graphs. In this work, we propose an iterative methodology to extract an application-specific gold standard dataset from a knowledge graph and an evaluation framework to comparatively assess the quality of noisy automatically extracted taxonomies. We employ an existing state of the art algorithm in an iterative manner and we propose several sampling strategies to reduce the amount of manual work needed for evaluation. A first gold standard dataset is released to the research community for this task along with a companion evaluation framework. This dataset addresses a real-world application from the medical domain, namely the extraction of food-drug and herb-drug interactions.

OBJECTIVES: The aim of this research was to automate the search of publications concerning adverse drug reactions (ADR) by defining the queries used to search MEDLINE and by determining the required threshold for the number of extracted publications to confirm the drug/event association in the literature. METHODS: We defined an approach based on the medical subject headings (MeSH) 'descriptor records' and 'supplementary concept records' thesaurus, using the subheadings 'chemically induced' and 'adverse effects' with the 'pharmacological action' knowledge. An expert-built validation set of true positive and true negative drug/adverse event associations (n=61) was used to validate our method. RESULTS: Using a threshold of three of more extracted publications, the automated search method presented a sensitivity of 90% and a specificity of 100%. For nine different drug/event pairs selected, the recall of the automated search ranged from 24% to 64% and the precision from 93% to 48%. CONCLUSIONS: This work presents a method to find previously established relationships between drugs and adverse events in the literature. Using MEDLINE, following a MeSH approach to filter the signals, is a valid option. Our contribution is available as a web service that will be integrated in the final European EU-ADR project (Exploring and Understanding Adverse Drug Reactions by integrative mining of clinical records and biomedical knowledge) automated system.

Drug safety issues pose serious health threats to the population and constitute a major cause of mortality worldwide. Due to the prominent implications to both public health and the pharmaceutical industry, it is of great importance to unravel the molecular mechanisms by which an adverse drug reaction can be potentially elicited. These mechanisms can be investigated by placing the pharmaco-epidemiologically detected adverse drug reaction in an information-rich context and by exploiting all currently available biomedical knowledge to substantiate it. We present a computational framework for the biological annotation of potential adverse drug reactions. First, the proposed framework investigates previous evidences on the drug-event association in the context of biomedical literature (signal filtering). Then, it seeks to provide a biological explanation (signal substantiation) by exploring mechanistic connections that might explain why a drug produces a specific adverse reaction. The mechanistic connections include the activity of the drug, related compounds and drug metabolites on protein targets, the association of protein targets to clinical events, and the annotation of proteins (both protein targets and proteins associated with clinical events) to biological pathways. Hence, the workflows for signal filtering and substantiation integrate modules for literature and database mining, in silico drug-target profiling, and analyses based on gene-disease networks and biological pathways. Application examples of these workflows carried out on selected cases of drug safety signals are discussed. The methodology and workflows presented offer a novel approach to explore the molecular mechanisms underlying adverse drug reactions.

BACKGROUND: Semantically-enriched browsing has enhanced the browsing experience by providing contextualized dynamically generated Web content, and quicker access to searched-for information. However, adoption of Semantic Web technologies is limited and user perception from the non-IT domain sceptical. Furthermore, little attention has been given to evaluating semantic browsers with real users to demonstrate the enhancements and obtain valuable feedback. The Sealife project investigates semantic browsing and its application to the life science domain. Sealife's main objective is to develop the notion of context-based information integration by extending three existing Semantic Web browsers (SWBs) to link the existing Web to the eScience infrastructure. METHODS: This paper describes a user-centred evaluation framework that was developed to evaluate the Sealife SWBs that elicited feedback on users' perceptions on ease of use and information findability. Three sources of data: i) web server logs; ii) user questionnaires; and iii) semi-structured interviews were analysed and comparisons made between each browser and a control system. RESULTS: It was found that the evaluation framework used successfully elicited users' perceptions of the three distinct SWBs. The results indicate that the browser with the most mature and polished interface was rated higher for usability, and semantic links were used by the users of all three browsers. CONCLUSION: Confirmation or contradiction of our original hypotheses with relation to SWBs is detailed along with observations of implementation issues.

The semantic Web vision relies on metadata and semantic annotation to be implemented on real world data. Ontologies and ontology-like artefacts are the key component providing necessary knowledge for Web document description. Domain ontology building is, however, a difficult and time consuming task. In this paper, we present our process of building an infection domain vocabulary for the national electronic library of infection. This paper describes the requirements for the vocabulary development process and the initial results.