Systems Bioinformatics: increasing precision of computational diagnostics and therapeutics through network-based approaches

Abstract

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.

Metabolomics to Improve the Diagnostic Efficiency of Inborn Errors of Metabolism

“…In one example, additional information on urine organic acid analysis was derived that could inform on treatment compliance [82]. Data generated from semi-targeted LC-MS/MS platforms could also be interrogated [54,56], were this to be linked with data on new diagnoses made through other methods, such as genomics [83]. The power here rests with creating linked datasets and bi-directionally mining them, as a form of systematic examination.…”

“…The power here rests with creating linked datasets and bi-directionally mining them, as a form of systematic examination. As with the advent of untargeted genomic testing (whole exome and genome sequencing), untargeted and semi-targeted metabolomic approaches provide a platform for the development of new disease biomarkers in situ [84], that is development, validation and repurposing for new clinical purposes while continuing to measure them for their existing intentions [83]. This underpins the notion for rapid translation from research into practice.…”

Investigating the Transition of Pre-Symptomatic to Symptomatic Huntington’s Disease Status Based on Omics Data

“…SB is an interdisciplinary field which combines the research fields of systems biology and bioinformatics. SB allows the integration of biological data across the omics categories such a genomics, transcriptomics, proteomics, metabolomics, lipidomics, epigenomics and several types of omics data [ 7 ].…”

IHS: an integrative method for the identification of network hubs

“…del Rio et al (2009) by analyzing 16 well-known centrality measures demonstrated that while identification of network hubs based on a single centrality measure is not statistically significant, the combination of two centrality measures that involve both local and global features of the network could more reliably predict the most influential nodes (del Rio et al, 2009). In systems biology studies, nodes with high degree and betweenness centrality are usually represented as network hubs in the context of defining both local significance and global network flow (Fu et al, 2015;Oulas et al, 2019). However, no method or algorithm has been developed to date that integrates these centrality measures with the purpose of synergizing their effects.…”