GOssTo: a stand-alone application and a web tool for calculating semantic similarities on the Gene Ontology.

SUMMARY: We present GOssTo, the Gene Ontology semantic similarity Tool, a user-friendly software system for calculating semantic similarities between gene products according to the Gene Ontology. GOssTo is bundled with six semantic similarity measures, including both term- and graph-based measures, and has extension capabilities to allow the user to add new similarities. Importantly, for any measure, GOssTo can also calculate the Random Walk Contribution that has been shown to greatly improve the accuracy of similarity measures. GOssTo is very fast, easy to use, and it allows the calculation of similarities on a genomic scale in a few minutes on a regular desktop machine. CONTACT: alberto@cs.rhul.ac.uk AVAILABILITY: GOssTo is available both as a stand-alone application running on GNU/Linux, Windows and MacOS from www.paccanarolab.org/gossto and as a web application from www.paccanarolab.org/gosstoweb. The stand-alone application features a simple and concise command line interface for easy integration into high-throughput data processing pipelines.

LanDis: the disease landscape explorer.

From a network medicine perspective, a disease is the consequence of perturbations on the interactome. These perturbations tend to appear in a specific neighbourhood on the interactome, the disease module, and modules related to phenotypically similar diseases tend to be located in close-by regions. We present LanDis, a freely available web-based interactive tool ( https://paccanarolab.org/landis ) that allows domain experts, medical doctors and the larger scientific community to graphically navigate the interactome distances between the modules of over 44 million pairs of heritable diseases. The map-like interface provides detailed comparisons between pairs of diseases together with supporting evidence. Every disease in LanDis is linked to relevant entries in OMIM and UniProt, providing a starting point for in-depth analysis and an opportunity for novel insight into the aetiology of diseases as well as differential diagnosis.

Safety of International Professional Sports Competitions During the COVID-19 Pandemic: The Association Football Experience.

Major sporting events were suspended during the most acute phase of the COVID-19 pandemic. Competitions are resuming with enhanced hygiene protocols and altered mechanics. While risks for players and staff have been studied, the impact of large-scale tournaments on the communities that host them remains largely unstudied. CONMEBOL Copa América is one of the first wide-scale international tournaments to be conducted in its original format since the beginning of the COVID-19 pandemic. The tournament saw 10 national teams compete in four Brazilian cities during a period of heightened viral transmission. The analysis of over 28,000 compulsory PCR tests showed that positive cases did not lead to the uncontrolled spread of the disease among staff and players. More importantly, the data indicate that locally hired staff were not exposed to increased risk while working. The Copa América experience shows that international sporting competitions can be conducted safely even under unfavourable epidemiological situations.

A network medicine approach to quantify distance between hereditary disease modules on the interactome.

We introduce a MeSH-based method that accurately quantifies similarity between heritable diseases at molecular level. This method effectively brings together the existing information about diseases that is scattered across the vast corpus of biomedical literature. We prove that sets of MeSH terms provide a highly descriptive representation of heritable disease and that the structure of MeSH provides a natural way of combining individual MeSH vocabularies. We show that our measure can be used effectively in the prediction of candidate disease genes. We developed a web application to query more than 28.5 million relationships between 7,574 hereditary diseases (96% of OMIM) based on our similarity measure.

An extensive analysis of disease-gene associations using network integration and fast kernel-based gene prioritization methods.

OBJECTIVE: In the context of "network medicine", gene prioritization methods represent one of the main tools to discover candidate disease genes by exploiting the large amount of data covering different types of functional relationships between genes. Several works proposed to integrate multiple sources of data to improve disease gene prioritization, but to our knowledge no systematic studies focused on the quantitative evaluation of the impact of network integration on gene prioritization. In this paper, we aim at providing an extensive analysis of gene-disease associations not limited to genetic disorders, and a systematic comparison of different network integration methods for gene prioritization. MATERIALS AND METHODS: We collected nine different functional networks representing different functional relationships between genes, and we combined them through both unweighted and weighted network integration methods. We then prioritized genes with respect to each of the considered 708 medical subject headings (MeSH) diseases by applying classical guilt-by-association, random walk and random walk with restart algorithms, and the recently proposed kernelized score functions. RESULTS: The results obtained with classical random walk algorithms and the best single network achieved an average area under the curve (AUC) across the 708 MeSH diseases of about 0.82, while kernelized score functions and network integration boosted the average AUC to about 0.89. Weighted integration, by exploiting the different "informativeness" embedded in different functional networks, outperforms unweighted integration at 0.01 significance level, according to the Wilcoxon signed rank sum test. For each MeSH disease we provide the top-ranked unannotated candidate genes, available for further bio-medical investigation. CONCLUSIONS: Network integration is necessary to boost the performances of gene prioritization methods. Moreover the methods based on kernelized score functions can further enhance disease gene ranking results, by adopting both local and global learning strategies, able to exploit the overall topology of the network.