The emerging high-throughput technologies have led to the shift in the design of translational medicine projects towards collecting multi-omics patient samples and, consequently, their integrated analysis. However, the complexity of integrating these datasets has triggered new questions regarding the appropriateness of the available computational methods. Currently, there is no clear consensus on the best combination of omics to include and the data integration methodologies required for their analysis. This article aims to guide the design of multi-omics studies in the field of translational medicine regarding the types of omics and the integration method to choose. We review articles that perform the integration of multiple omics measurements from patient samples. We identify five objectives in translational medicine applications: (i) detect disease-associated molecular patterns, (ii) subtype identification, (iii) diagnosis/prognosis, (iv) drug response prediction, and (v) understand regulatory processes. We describe common trends in the selection of omic types combined for different objectives and diseases. To guide the choice of data integration tools, we group them into the scientific objectives they aim to address. We describe the main computational methods adopted to achieve these objectives and present examples of tools. We compare tools based on how they deal with the computational challenges of data integration and comment on how they perform against predefined objective-specific evaluation criteria. Finally, we discuss examples of tools for downstream analysis and further extraction of novel insights from multi-omics datasets.

Systems Bioinformatics is a relatively new approach, which lies in the intersection of systems biology and classical bioinformatics. It focuses on integrating information across different levels using a bottom-up approach as in systems biology with a data-driven top-down approach as in bioinformatics. The advent of omics technologies has provided the stepping-stone for the emergence of Systems Bioinformatics. These technologies provide a spectrum of information ranging from genomics, transcriptomics and proteomics to epigenomics, pharmacogenomics, metagenomics and metabolomics. Systems Bioinformatics is the framework in which systems approaches are applied to such data, setting the level of resolution as well as the boundary of the system of interest and studying the emerging properties of the system as a whole rather than the sum of the properties derived from the system’s individual components. A key approach in Systems Bioinformatics is the construction of multiple networks representing each level of the omics spectrum and their integration in a layered network that exchanges information within and between layers. Here, we provide evidence on how Systems Bioinformatics enhances computational therapeutics and diagnostics, hence paving the way to precision medicine. The aim of this review is to familiarize the reader with the emerging field of Systems Bioinformatics and to provide a comprehensive overview of its current state-of-the-art methods and technologies. Moreover, we provide examples of success stories and case studies that utilize such methods and tools to significantly advance research in the fields of systems biology and systems medicine.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is undeniably the most severe global health emergency since the 1918 Influenza outbreak. Depending on its evolutionary trajectory, the virus is expected to establish itself as an endemic infectious respiratory disease exhibiting seasonal flare-ups. Therefore, despite the unprecedented rally to reach a vaccine that can offer widespread immunization, it is equally important to reach effective prevention and treatment regimens for coronavirus disease 2019 (COVID-19). Contributing to this effort, we have curated and analyzed multi-source and multi-omics publicly available data from patients, cell lines and databases in order to fuel a multiplex computational drug repurposing approach. We devised a network-based integration of multi-omic data to prioritize the most important genes related to COVID-19 and subsequently re-rank the identified candidate drugs. Our approach resulted in a highly informed integrated drug shortlist by combining structural diversity filtering along with experts’ curation and drug–target mapping on the depicted molecular pathways. In addition to the recently proposed drugs that are already generating promising results such as dexamethasone and remdesivir, our list includes inhibitors of Src tyrosine kinase (bosutinib, dasatinib, cytarabine and saracatinib), which appear to be involved in multiple COVID-19 pathophysiological mechanisms. In addition, we highlight specific immunomodulators and anti-inflammatory drugs like dactolisib and methotrexate and inhibitors of histone deacetylase like hydroquinone and vorinostat with potential beneficial effects in their mechanisms of action. Overall, this multiplex drug repurposing approach, developed and utilized herein specifically for SARS-CoV-2, can offer a rapid mapping and drug prioritization against any pathogen-related disease.

This study aims to highlight SARS-COV-2 mutations which are associated with increased or decreased viral virulence. We utilize genetic data from all strains available from GISAID and countries’ regional information, such as deaths and cases per million, as well as COVID-19-related public health austerity measure response times. Initial indications of selective advantage of specific mutations can be obtained from calculating their frequencies across viral strains. By applying modelling approaches, we provide additional information that is not evident from standard statistics or mutation frequencies alone. We therefore, propose a more precise way of selecting informative mutations. We highlight two interesting mutations found in genes N (P13L) and ORF3a (Q57H). The former appears to be significantly associated with decreased deaths and cases per million according to our models, while the latter shows an opposing association with decreased deaths and increased cases per million. Moreover, protein structure prediction tools show that the mutations infer conformational changes to the protein that significantly alter its structure when compared to the reference protein.

Summary: ChemBioServer 2.0 is the advanced sequel of a web server for filtering, clustering and networking of chemical compound libraries facilitating both drug discovery and repurposing. It provides researchers the ability to (i) browse and visualize compounds along with their physicochemical and toxicity properties, (ii) perform property-based filtering of compounds, (iii) explore compound libraries for lead optimization based on perfect match substructure search, (iv) re-rank virtual screening results to achieve selectivity for a protein of interest against different protein members of the same family, selecting only those compounds that score high for the protein of interest, (v) perform clustering among the compounds based on their physicochemical properties providing representative compounds for each cluster, (vi) construct and visualize a structural similarity network of compounds providing a set of network analysis metrics, (vii) combine a given set of compounds with a reference set of compounds into a single structural similarity network providing the opportunity to infer drug repurposing due to transitivity, (viii) remove compounds from a network based on their similarity with unwanted substances (e.g. failed drugs) and (ix) build custom compound mining pipelines. Availability and implementation: http://chembioserver.vi-seem.eu.

The abundance of available information for each disease from multiple sources (e.g. as genetic, regulatory, metabolic, and protein-protein interaction) constitutes both an advantage and a challenge in identifying disease-specific underlying mechanisms. Integration of multi-source data is a rising topic and a great challenge in precision medicine and is crucial in enhancing disease understanding, identifying meaningful clusters of molecular mechanisms and increasing precision and personalisation towards the goal of Predictive, Preventive and Personalised Medicine (PPPM). The overall aim of this work was to develop a novel network-based integration methodology with the following characteristics: (i) maximise the number of data sources, (ii) utilise holistic approaches to integrate these sources (iii) be simple, flexible and extendable, (iv) be conclusive. Here, we present the case of Alzheimer's disease as a paradigm for illustrating our novel approach. In this work we present an integration methodology, which aggregates a large number of the available data sources and types by exploiting the holistic nature of network approaches. It is simple, flexible and extendable generating solid conclusions regarding the molecular mechanisms that underlie the input data. We have illustrated the strength of our proposed methodology using Alzheimer's disease as a paradigm. This method is expected to serve as a stepping-stone for further development of integration methods of multi-source omic-data and to contribute to progress towards the goal of Predictive, Preventive and Personalised Medicine (PPPM). The output of this methodology may act as a reference map of implicated pathways in the disease under investigation, where pathways related to additional omics data from any kind of experiment may be projected. This will increase the precision in the understanding of the disease and may contribute to personalised approaches for patients with different disease-related pathway profile, leading to a more precise, personalised and ideally preventive management of the disease.