HYGIEIA: HYpothesizing the Genesis of Infectious Diseases and Epidemics through an Integrated Systems Biology Approach

Abstract

More than two years on, the COVID-19 pandemic continues to wreak havoc around the world and has battle-tested the pandemic-situation responses of all major global governments. Two key areas of investigation that are still unclear are: the molecular mechanisms that lead to heterogenic patient outcomes, and the causes of Post COVID condition (AKA Long-COVID). In this paper, we introduce the HYGIEIA project, designed to respond to the enormous challenges of the COVID-19 pandemic through a multi-omic approach supported by network medicine. It is hoped that in addition to investigating COVID-19, the logistics deployed within this project will be applicable to other infectious agents, pandemic-type situations, and also other complex, non-infectious diseases. Here, we first look at previous research into COVID-19 in the context of the proteome, metabolome, transcriptome, microbiome, host genome, and viral genome. We then discuss a proposed methodology for a large-scale multi-omic longitudinal study to investigate the aforementioned biological strata through high-throughput sequencing (HTS) and mass-spectrometry (MS) technologies. Lastly, we discuss how a network medicine approach can be used to analyze the data and make meaningful discoveries, with the final aim being the translation of these discoveries into the clinics to improve patient care.

Deep plasma proteomics with data-independent acquisition: A fastlane towards biomarkers identification

“…Utilising such a protocol can significantly reduce the cost, time, and complexity required in performing exploratory proteomic studies on human plasma and is currently being applied in our setting to a large, 200 +, multi-timepoint patient cohort in a multi-omics context 29 . control; FDR, False discovery rate; HYGIEIA, Hypothesizing the genesis of infectious diseases and epidemics through an integrated systems biology approach; AUC, Area under the curve; PCA, Principal component analysis; PC, Principal component; QC, Quality control; SDS, Sodium dodecyl-sulfate; logFC, Log fold change; NLM, National library of medicine…”

“…7 fractions are then concatenated into 3 pooled fractions, for a total MS run time of 360 minutes. Utilising such a protocol can significantly reduce the cost, time, and complexity required in performing exploratory proteomic studies on human plasma and is currently being applied in our setting to a large, 200 +, multi-timepoint patient cohort in a multi-omics context 29 .…”

“…The cohort included in this study comprises a 20 patient sub-cohort from the HYGIEIA study 29 . Patients were enrolled from August 2020 to December 2023.…”

NMR-Based Chromatography Readouts: Indispensable Tools to “Translate” Analytical Features into Molecular Structures

“…The accelerated knowledge transfer on the brink of the current pandemic [ 58 ], which was largely decoupled from scientific peer review, has clearly shown that it is of extraordinary importance to structurally characterize discriminators (“statistically”) found in in silico datasets. This is independent of experimental data sources, such as relative copy numbers of specific mRNA polymers (genomics and expression patterns), the pattern differences in 2D protein gels or highly complex mass spectra attributable to the peptides of sample proteins (proteomics and peptidomics), or even the secondary metabolite patterns in biological samples (metabolomics).…”