Network-based approaches to explore complex biological systems towards network medicine

Network medicine relies on different types of networks: from the molecular level of protein–protein interactions to gene regulatory network and correlation studies of gene expression. Among network approaches based on the analysis of the topological properties of protein–protein interaction (PPI) networks, we discuss the widespread DIAMOnD (disease module detection) algorithm. Starting from the assumption that PPI networks can be viewed as maps where diseases can be identified with localized perturbation within a specific neighborhood (i.e., disease modules), DIAMOnD performs a systematic analysis of the human PPI network to uncover new disease-associated genes by exploiting the connectivity significance instead of connection density. The past few years have witnessed the increasing interest in understanding the molecular mechanism of post-transcriptional regulation with a special emphasis on non-coding RNAs since they are emerging as key regulators of many cellular processes in both physiological and pathological states. Recent findings show that coding genes are not the only targets that microRNAs interact with. In fact, there is a pool of different RNAs—including long non-coding RNAs (lncRNAs) —competing with each other to attract microRNAs for interactions, thus acting as competing endogenous RNAs (ceRNAs). The framework of regulatory networks provides a powerful tool to gather new insights into ceRNA regulatory mechanisms. Here, we describe a data-driven model recently developed to explore the lncRNA-associated ceRNA activity in breast invasive carcinoma. On the other hand, a very promising example of the co-expression network is the one implemented by the software SWIM (switch miner), which combines topological properties of correlation networks with gene expression data in order to identify a small pool of genes—called switch genes—critically associated with drastic changes in cell phenotype. Here, we describe SWIM tool along with its applications to cancer research and compare its predictions with DIAMOnD disease genes

EEVi – framework for evaluating the effectiveness of visualization in cyber-security

Cyber-security visualization is an up-and-coming area which aims to reduce security analysts’ workload by presenting information as visual analytics rather than a string of text and characters. But the adoption of the resultant visualizations has not increased. The literature indicates a research gap of a lack of guidelines and standardized evaluation techniques for effective visualization in cyber-security, as a reason for it. Therefore, this research addresses the research gap by developing a framework called EEVi for effective cyber-security visualizations for the performed task. The term ‘effective visualization’ can be defined as the features of visualization that are crucial to perform a certain task successfully. EEVi has been developed by analyzing qualitative data that leads to the formation of cognitive relationships (called links) between data that act as guidelines for effective cyber-security visualization in terms of the performed task. The methodology to develop this framework can be applied to other fields to understand cognitive relationships between data. Additionally, the analysis presents a glimpse into the usage of EEVi in cyber-security visualization

SAveRUNNER: a network-based algorithm for drug repurposing and its application to COVID-19

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, comorbidity, or for their association to drugs tentatively repurposed to treat COVID-19. Focusing specifically on SARS subnetwork, we identified 282 repurposable drugs, including some the most rumored off-label drugs for COVID-19 treatments, as well as a new combination therapy of 5 drugs, 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, 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.Comment: 42 pages, 9 figure

Assessing a requirements evolution approach: Empirical studies in the air traffic management domain

In this paper, we report the results of the empirical evaluation of a novel approach for modeling and reasoning on evolving requirements. We evaluated the effectiveness of the approach in modeling requirements evolution by means of a series of empirical studies in the air traffic management (ATM) domain

Formal modelling of data integration systems security policies

Data Integration Systems (DIS) are concerned with integrating data from multiple data sources to resolve user queries. Typically, organisations providing data sources specify security policies that impose stringent requirements on the collection, processing, and disclosure of personal and sensitive data. If the security policies were not correctly enforced by the integration component of DIS, the data is exposed to data leakage threats, e.g. unauthorised disclosure or secondary use of the data. SecureDIS is a framework that helps system designers to mitigate data leakage threats during the early phases of DIS development. SecureDIS provides designers with a set of informal guidelines written in natural language to specify and enforce security policies that capture confidentiality, privacy, and trust properties. In this paper, we apply a formal approach to model a DIS with the SecureDIS security policies and verify the correctness and consistency of the model. The model can be used as a basis to perform security policies analysis or automatically generate a Java code to enforce those policies within DIS

Decentralised runtime monitoring for access control systems in cloud federations

Cloud federation is an emergent cloud-computing paradigm where partner organisations share data and services hosted on their own cloud platforms. In this context, it is crucial to enforce access control policies that satisfy data protection and privacy requirements of partner organisations. However, due to the distributed nature of cloud federations, the access control system alone does not guarantee that its deployed components cannot be circumvented while processing access requests. In order to promote accountability and reliability of a distributed access control system, we present a decentralised runtime monitoring architecture based on blockchain technology

The oncogenic role of circPVT1 in head and neck squamous cell carcinoma is mediated through the mutant p53/YAP/TEAD transcription-competent complex

Background: Circular RNAs are a class of endogenous RNAs with various functions in eukaryotic cells. Worthy of note, circular RNAs play a critical role in cancer. Currently, nothing is known about their role in head and neck squamous cell carcinoma (HNSCC). The identification of circular RNAs in HNSCC might become useful for diagnostic and therapeutic strategies in HNSCC. Results: Using samples from 115 HNSCC patients, we find that circPVT1 is over-expressed in tumors compared to matched non-tumoral tissues, with particular enrichment in patients with TP53 mutations. circPVT1 up-and down-regulation determine, respectively, an increase and a reduction of the malignant phenotype in HNSCC cell lines. We show that circPVT1 expression is transcriptionally enhanced by the mut-p53/YAP/TEAD complex. circPVT1 acts as an oncogene modulating the expression of miR-497-5p and genes involved in the control of cell proliferation. Conclusions: This study shows the oncogenic role of circPVT1 in HNSCC, extending current knowledge about the role of circular RNAs in cancer