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. 2022 Apr 28;13:2299. doi: 10.1038/s41467-022-29998-8

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — a Flow chart depicting the validation approaches. b Single nucleotide polymorphism (SNP) affected genes differentially expressed in ulcerative colitis (UC) patients from biopsy samples of the GSE109142 dataset. Absolute log2 fold change > 1 was used as a cut-off. c The percentage of differentially expressed genes from the first neighbours of the cluster-driving proteins using the same dataset. Analysis of the patients in the independent cohort produced two clusters similar to those generated by iSNP (red and purple cluster on Fig. 3B). The most differentially expressed genes from the UC-associated signalling network in the validation cohort were the first neighbours of multiple SNP-affected proteins. d Similarities between the over-represented Gene Ontology Biological Processes between first neighbours of cluster-driving proteins and differentially expressed genes. Gene Ontology terms were considered enriched based on a Benjamini-Hochberg corrected hypergeometric test p < 0.05. A gene was considered differentially expressed based on |FC| > 1 and q < 0.05 Benjamini-Hochberg corrected moderate t-test There are two main groups of Gene Ontology Biological Processes: common and specific. The common processes include regulation of signalling or metabolic processes while the specific processes represent the cluster-driving protein and its cluster function or the transcriptomic effect of inflammation. Differentially expressed genes, first neighbours, or functions are represented in yellow and the cluster-driving genes are represented by their respective colours: pink—SNAI1, CEBPB, PTPN1; blue—PRKCB; orange—VEGFA, XPO5, POLH; purple—NFKB1, turquoise—HLA proteins.