Drug Side Effect Prediction with Deep Learning Molecular Embedding in a Graph-of-Graphs Domain

Drug side effects (DSEs), or adverse drug reactions (ADRs), constitute an important health risk, given the approximately 197,000 annual DSE deaths in Europe alone. Therefore, during the drug development process, DSE detection is of utmost importance, and the occurrence of ADRs prevents many candidate molecules from going through clinical trials. Thus, early prediction of DSEs has the potential to massively reduce drug development times and costs. In this work, data are represented in a non-euclidean manner, in the form of a graph-of-graphs domain. In such a domain, structures of molecule are represented by molecular graphs, each of which becomes a node in the higher-level graph. In the latter, nodes stand for drugs and genes, and arcs represent their relationships. This relational nature represents an important novelty for the DSE prediction task, and it is directly used during the prediction. For this purpose, the MolecularGNN model is proposed. This new classifier is based on graph neural networks, a connectionist model capable of processing data in the form of graphs. The approach represents an improvement over a previous method, called DruGNN, as it is also capable of extracting information from the graph-based molecular structures, producing a task-based neural fingerprint (NF) of the molecule which is adapted to the specific task. The architecture has been compared with other GNN models in terms of performance, showing that the proposed approach is very promising

Visual Question Answering for Cultural Heritage

International Conference Florence Heri-Tech is a conference about the technology applied to cultural heritage. This conference involves different areas and topics like engineering, material science, digital heritage..

Visual Question Answering for Cultural Heritage

Technology and the fruition of cultural heritage are becoming increasingly more entwined, especially with the advent of smart audio guides, virtual and augmented reality, and interactive installations. Machine learning and computer vision are important components of this ongoing integration, enabling new interaction modalities between user and museum. Nonetheless, the most frequent way of interacting with paintings and statues still remains taking pictures. Yet images alone can only convey the aesthetics of the artwork, lacking is information which is often required to fully understand and appreciate it. Usually this additional knowledge comes both from the artwork itself (and therefore the image depicting it) and from an external source of knowledge, such as an information sheet. While the former can be inferred by computer vision algorithms, the latter needs more structured data to pair visual content with relevant information. Regardless of its source, this information still must be be effectively transmitted to the user. A popular emerging trend in computer vision is Visual Question Answering (VQA), in which users can interact with a neural network by posing questions in natural language and receiving answers about the visual content. We believe that this will be the evolution of smart audio guides for museum visits and simple image browsing on personal smartphones. This will turn the classic audio guide into a smart personal instructor with which the visitor can interact by asking for explanations focused on specific interests. The advantages are twofold: on the one hand the cognitive burden of the visitor will decrease, limiting the flow of information to what the user actually wants to hear; and on the other hand it proposes the most natural way of interacting with a guide, favoring engagement.Comment: accepted at FlorenceHeritech 202

VISCOUNTH: A Large-Scale Multilingual Visual Question Answering Dataset for Cultural Heritage

Visual question answering has recently been settled as a fundamental multi-modal reasoning task of artificial intelligence that allows users to get information about visual content by asking questions in natural language. In the cultural heritage domain this task can contribute to assist visitors in museums and cultural sites, thus increasing engagement. However, the development of visual question answering models for cultural heritage is prevented by the lack of suitable large-scale datasets. To meet this demand, we built a large-scale heterogeneous and multilingual (Italian and English) dataset for cultural heritage that comprises approximately 500K Italian cultural assets and 6.5M question-answer pairs. We propose a novel formulation of the task that requires reasoning over both the visual content and an associated natural language description, and present baselines for this task. Results show that the current state of the art is reasonably effective, but still far from satisfactory, therefore further research is this area is recommended. Nonetheless, we also present a holistic baseline to address visual and contextual questions and foster future research on the topic

Molecular generative Graph Neural Networks for Drug Discovery

Drug Discovery is a fundamental and ever-evolving field of research. The design of new candidate molecules requires large amounts of time and money, and computational methods are being increasingly employed to cut these costs. Machine learning methods are ideal for the design of large amounts of potential new candidate molecules, which are naturally represented as graphs. Graph generation is being revolutionized by deep learning methods, and molecular generation is one of its most promising applications. In this paper, we introduce a sequential molecular graph generator based on a set of graph neural network modules, which we call MG2N2. At each step, a node or a group of nodes is added to the graph, along with its connections. The modular architecture simplifies the training procedure, also allowing an independent retraining of a single module. Sequentiality and modularity make the generation process interpretable. The use of Graph Neural Networks maximizes the information in input at each generative step, which consists of the subgraph produced during the previous steps. Experiments of unconditional generation on the QM9 and Zinc datasets show that our model is capable of generalizing molecular patterns seen during the training phase, without overfitting. The results indicate that our method is competitive, and outperforms challenging baselines for unconditional generation

Glycine induced formation and druggability score prediction of protein surface pockets

Nowadays, it is well established that most of the human diseases which are not related to pathogen infections have their origin from DNA disorders. Thus, DNA mutations, waiting for the availability of CRISPR-like remedies, will propagate into proteomics, offering the possibility to select natural or synthetic molecules to fight against the effects of malfunctioning proteins. Drug discovery, indeed, is a flourishing field of biotechnological research to improve human health, even though the development of a new drug is increasingly more expensive in spite of the massive use of informatics in Medicinal Chemistry. CRISPR technology adds new alternatives to cure diseases by removing DNA defects responsible of genome-related pathologies. In principle, the same technology, however, could also be exploited to induce protein mutations whose effects are controlled by the presence of suitable ligands. In this paper, a new idea is proposed for the realization of mutated proteins, on the surface of which more spacious transient pockets are formed and, therefore, are more suitable for hosting drugs. In particular, new allosteric sites are obtained by replacing amino-acids with bulky side chains with glycine, Gly, the smallest natural amino-acid. We also present a machine learning approach to evaluate the druggability score of new (or enlarged) pockets. Preliminary experimental results are very promising, showing that 10% of the sites created by the Gly-pipe software are druggable

A Deep Learning Approach to the Prediction of Drug Side-Effects on Molecular Graphs

: Predicting drug side effects before they occur is a critical task for keeping the number of drug-related hospitalizations low and for improving drug discovery processes. Automatic predictors of side-effects generally are not able to process the structure of the drug, resulting in a loss of information. Graph neural networks have seen great success in recent years, thanks to their ability of exploiting the information conveyed by the graph structure and labels. These models have been used in a wide variety of biological applications, among which the prediction of drug side-effects on a large knowledge graph. Exploiting the molecular graph encoding the structure of the drug represents a novel approach, in which the problem is formulated as a multi-class multi-label graph-focused classification. We developed a methodology to carry out this task, using recurrent Graph Neural Networks, and building a dataset from freely accessible and well established data sources. The results show that our method has an improved classification capability, under many parameters and metrics, with respect to previously available predictors. The method is not ready for clinical tests yet, as the specificity is still below the preliminary 25 % threshold. Future efforts will aim at improving this aspect

Modular multi-source prediction of drug side-effects with DruGNN

Drug Side-Effects (DSEs) have a high impact on public health, care system costs, and drug discovery processes. Predicting the probability of side-effects, before their occurrence, is fundamental to reduce this impact, in particular on drug discovery. Candidate molecules could be screened before undergoing clinical trials, reducing the costs in time, money, and health of the participants. Drug side-effects are triggered by complex biological processes involving many different entities, from drug structures to protein-protein interactions. To predict their occurrence, it is necessary to integrate data from heterogeneous sources. In this work, such heterogeneous data is integrated into a graph dataset, expressively representing the relational information between different entities, such as drug molecules and genes. The relational nature of the dataset represents an important novelty for drug side-effect predictors. Graph Neural Networks (GNNs) are exploited to predict DSEs on our dataset with very promising results. GNNs are deep learning models that can process graph-structured data, with minimal information loss, and have been applied on a wide variety of biological tasks. Our experimental results confirm the advantage of using relationships between data entities, suggesting interesting future developments in this scope. The experimentation also shows the importance of specific subsets of data in determining associations between drugs and side-effects

Structural Bioinformatics to unveil weaknesses of coronavirus spike glycoprotein stability

Alternative strategies for developing antiviral drugs are needed, as vaccines could not be the final answer against the present SARS CoV-2 outbreak, due to the still existing ambiguities in the immunological response to the virus. Thus, SARS CoV-2 enzymes have been thoroughly investigated to develop their inhibitors as antiviral drugs. We have searched the latter antiviral drugs among those small molecules that can interfere with the trimeric assembly of the S glycoprotein. We have systematically explored the trimer interfaces in the search of pockets that can be suitable for ligand binding. Virtual screening of FDA approved drug library confirmed that concave moieties of S glycoprotein protomer interfaces can act as binding sites of small molecules. Interfering with S glycoprotein quaternary assembly, these small molecules would represent an alternative family of antiviral drugs