Background: miRNAs regulate the expression of several genes with one miRNA able to target multiple genes and with one gene able to be simultaneously targeted by more than one miRNA. Therefore, it has become indispensable to shorten the long list of miRNA-target interactions to put in the spotlight in order to gain insight into understanding the regulatory mechanism orchestrated by miRNAs in various cellular processes. A reasonable solution is certainly to prioritize miRNA-target interactions to maximize the effectiveness of the downstream analysis. Results: We propose a new and easy-to-use web tool MIENTURNET (MicroRNA ENrichment TURned NETwork) that receives in input a list of miRNAs or mRNAs and tackles the problem of prioritizing miRNA-target interactions by performing a statistical analysis followed by a fully featured network-based visualization and analysis. The statistics is used to assess the significance of an over-representation of miRNA-target interactions and then MIENTURNET filters based on the statistical significance associated with each miRNA-target interaction. In addition, the holistic approach of the network theory is used to infer possible evidences of miRNA regulation by capturing emergent properties of the miRNA-target regulatory network that would be not evident through a pairwise analysis of the individual components. Conclusion: MIENTURNET offers the possibility to consistently perform both statistical and network-based analyses by using only a single tool leading to a more effective prioritization of the miRNA-target interactions. This has the potential to avoid researchers without computational and informatics skills to navigate multiple websites and thus to independently investigate miRNA activity in every cellular process of interest in an easy and at the same time exhaustive way thanks to the intuitive web interface. The web application along with a well-documented and comprehensive user guide are freely available at http://userver.bio.uniroma1.it/apps/mienturnet/ without any login requirement.

Alzheimer’s Disease (AD) is a neurodegenaritive disorder characterized by a progressive dementia, for which actually no cure is known. An early detection of patients affected by AD can be obtained by analyzing their electroencephalography (EEG) signals, which show a reduction of the complexity, a perturbation of the synchrony, and a slowing down of the rhythms. In this work, we apply a procedure that exploits feature extraction and classification techniques to EEG signals, whose aim is to distinguish patient affected by AD from the ones affected by Mild Cognitive Impairment (MCI) and healthy control (HC) samples. Specifically, we perform a time-frequency analysis by applying both the Fourier and Wavelet Transforms on 109 samples belonging to AD, MCI, and HC classes. The classification procedure is designed with the following steps: (i) preprocessing of EEG signals; (ii) feature extraction by means of the Discrete Fourier and Wavelet Transforms; and (iii) classification with tree-based supervised methods. By applying our procedure, we are able to extract reliable human-interpretable classification models that allow to automatically assign the patients into their belonging class. In particular, by exploiting a Wavelet feature extraction we achieve 83%, 92%, and 79% of accuracy when dealing with HC vs AD, HC vs MCI, and MCI vs AD classification problems, respectively. Finally, by comparing the classification performances with both feature extraction methods, we find out that Wavelets analysis outperforms Fourier. Hence, we suggest it in combination with supervised methods for automatic patients classification based on their EEG signals for aiding the medical diagnosis of dementia.

The novelty of new human coronavirus COVID-19/SARS-CoV-2 and the lack of effective drugs and vaccines gave rise to a wide variety of strategies employed to fight this worldwide pandemic. Many of these strategies rely on the repositioning of existing drugs that could shorten the time and reduce the cost compared to de novo drug discovery. In this study, we presented a new network-based algorithm for drug repositioning, called SAveRUNNER (Searching off-lAbel dRUg aNd NEtwoRk), which predicts drug–disease associations by quantifying the interplay between the drug targets and the disease-specific proteins in the human interactome via a novel network-based similarity measure that prioritizes associations between drugs and diseases locating in the same network neighborhoods. Specifically, we applied SAveRUNNER on a panel of 14 selected diseases with a consolidated knowledge about their disease-causing genes and that have been found to be related to COVID-19 for genetic similarity (i.e., SARS), comorbidity (e.g., cardiovascular diseases), or for their association to drugs tentatively repurposed to treat COVID-19 (e.g., malaria, HIV, rheumatoid arthritis). Focusing specifically on SARS subnetwork, we identified 282 repurposable drugs, including some the most rumored off-label drugs for COVID-19 treatments (e.g., chloroquine, hydroxychloroquine, tocilizumab, heparin), as well as a new combination therapy of 5 drugs (hydroxychloroquine, chloroquine, lopinavir, ritonavir, remdesivir), actually used in clinical practice. Furthermore, to maximize the efficiency of putative downstream validation experiments, we prioritized 24 potential anti-SARS-CoV repurposable drugs based on their network-based similarity values. These top-ranked drugs include ACE-inhibitors, monoclonal antibodies (e.g., anti-IFNγ, anti-TNFα, anti-IL12, anti-IL1β, anti-IL6), and thrombin inhibitors. Finally, our findings were in-silico validated by performing a gene set enrichment analysis, which confirmed that most of the network-predicted repurposable drugs may have a potential treatment effect against human coronavirus infections.

In this study, we integrate the outcomes of co-expression network analysis with the human interactome network to predict novel putative disease genes and modules. We first apply the SWItch Miner (SWIM) methodology, which predicts important (switch) genes within the co-expression network that regulate disease state transitions, then map them to the human protein–protein interaction network (PPI, or interactome) to predict novel disease–disease relationships (i.e., a SWIM-informed diseasome). Although the relevance of switch genes to an observed phenotype has been recently assessed, their performance at the system or network level constitutes a new, potentially fascinating territory yet to be explored. Quantifying the interplay between switch genes and human diseases in the interactome network, we found that switch genes associated with specific disorders are closer to each other than to other nodes in the network, and tend to form localized connected subnetworks. These subnetworks overlap between similar diseases and are situated in different neighborhoods for pathologically distinct phenotypes, consistent with the well-known topological proximity property of disease genes. These findings allow us to demonstrate how SWIM-based correlation network analysis can serve as a useful tool for efficient screening of potentially new disease gene associations. When integrated with an interactome-based network analysis, it not only identifies novel candidate disease genes, but also may offer testable hypotheses by which to elucidate the molecular underpinnings of human disease and reveal commonalities between seemingly unrelated diseases.