The SYSCID map: a graphical and computational resource of molecular mechanisms across rheumatoid arthritis, systemic lupus erythematosus and inflammatory bowel disease#
Authors#
Marcio Luis Acencio, Marek Ostaszewski, Alexander Mazein, Philip Rosenstiel, Konrad Aden, Neha Mishra, Vibeke Andersen, Prodromos Sidiropoulos, Aggelos Banos, Anastasia Filia, Souad Rahmouni, Axel Finckh, Wei Gu, Reinhard Schneider, Venkata Pardhasaradhi Satagopam
Abstract#
Chronic inflammatory diseases (CIDs), including inflammatory bowel disease (IBD), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are thought to emerge from an impaired complex network of inter- and intracellular biochemical interactions among several proteins and small chemical compounds under strong influence of genetic and environmental factors. CIDs are characterised by shared and disease-specific processes, which is reflected by partially overlapping genetic risk maps and pathogenic cells (e.g., T cells). Their pathogenesis involves a plethora of intracellular pathways. The translation of the research findings on CIDs molecular mechanisms into effective treatments is challenging and may explain the low remission rates despite modern targeted therapies. Modelling CID-related causal interactions as networks allows us to tackle the complexity at a systems level and improve our understanding of the interplay of key pathways. Here we report the construction, description, and initial applications of the SYSCID map (https://syscid.elixir-luxembourg.org/), a mechanistic causal interaction network covering the molecular crosstalk between IBD, RA and SLE. We demonstrate that the map serves as an interactive, graphical review of IBD, RA and SLE molecular mechanisms, and helps to understand the complexity of omics data. Examples of such application are illustrated using transcriptome data from time-series gene expression profiles following anti-TNF treatment and data from genome-wide associations studies that enable us to suggest potential effects to altered pathways and propose possible mechanistic biomarkers of treatment response.
Data Availability Statement#
The map generated and analyzed in this study can be found in the ELIXIR Luxembourg’s MINERVA platform at https://syscid.elixir-luxembourg.org/. The original version of the transcriptome dataset integrated to the map can be found at the Gene Expression Omnibus (GEO) website under the accession number GSE191328 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE191328. The MINERVA-adapted version of the integrated transcriptome dataset can be found embedded in the own map under the tab “OVERLAYS” or in the Supplementary Table S6. The IBD-, RA- and SLE-associated genetic variant datasets collected from the GWAS catalog https://www.ebi.ac.uk/gwas/ can be found embedded in the own map under the tab “OVERLAYS” and in the Supplementary Tables S2-S5. The list of publications curated for building the map can be found in the own map under the tab “Info” or in the Supplementary Table S10.
