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High-Throughput Identification of the Plasma Proteomic Signature of Inflammatory Bowel Disease.

ABSTRACT: BACKGROUND:The molecular aetiology of inflammatory bowel disease [IBD] and its two subtypes, ulcerative colitis [UC] and Crohn's disease [CD], have been carefully investigated at genome and transcriptome levels. Recent advances in high-throughput proteome quantification has enabled comprehensive large-scale plasma proteomics studies of IBD. METHODS:The study used two cohorts: [1] The CERTIFI-cohort: 42 samples from the CERTIFI trial of anti-TNF?-refractory CD patients; [2] the PROgECT-UNITI-HCs cohort: 46 UC samples of the PROgECT study, 84 CD samples of the UNITI I and UNITI II studies, and 72 healthy controls recruited in Mount Sinai Hospital, New York, USA. The plasma proteome for these two cohorts was quantified using high-throughput platforms. RESULTS:For the PROgECT-UNITI-HCs cohort, we measured a total of 1310 proteins. Of these, 493 proteins showed different plasma levels in IBD patients to the plasma levels in controls at 10% false discovery rate [FDR], among which 11 proteins had a fold change greater than 2. The proteins upregulated in IBD were associated with immunity functionality, whereas the proteins downregulated in IBD were associated with nutrition and metabolism. The proteomic profiles were very similar between UC and CD. In the CERTIFI cohort, 1014 proteins were measured, and it was found that the plasma protein level had little correlation with the blood or intestine transcriptomes. CONCLUSIONS:We report the largest proteomics study to date on IBD and controls. A large proportion of plasma proteins are altered in IBD, which provides insights into the disease aetiology and indicates a potential for biomarker discovery.

SUBMITTER: Di Narzo AF

PROVIDER: S-EPMC6441306 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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High-Throughput Identification of the Plasma Proteomic Signature of Inflammatory Bowel Disease.

Di Narzo Antonio F AF Brodmerkel Carrie C Telesco Shannon E SE Argmann Carmen C Peters Lauren A LA Li Katherine K Kidd Brian B Dudley Joel J Cho Judy J Schadt Eric E EE Kasarskis Andrew A Dobrin Radu R Hao Ke K

Journal of Crohn's & colitis 20190301 4

<h4>Background</h4>The molecular aetiology of inflammatory bowel disease [IBD] and its two subtypes, ulcerative colitis [UC] and Crohn's disease [CD], have been carefully investigated at genome and transcriptome levels. Recent advances in high-throughput proteome quantification has enabled comprehensive large-scale plasma proteomics studies of IBD.<h4>Methods</h4>The study used two cohorts: [1] The CERTIFI-cohort: 42 samples from the CERTIFI trial of anti-TNFα-refractory CD patients; [2] the PRO ...[more]

PMID: 30445421

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Project description:BackgroundInflammatory bowel diseases (IBD) refer to a group of inflammatory conditions concerning colon and small intestine, which cause socially uncomfortable symptoms and often are associated with an increased risk of colon cancer. IBD are complex disorders, which rely on genetic susceptibility, environmental factors, deregulation of the immune system, and host relationship with commensal microbiota. The complexity of these pathologies makes difficult to clearly understand the mechanisms of their onset. Therefore, the study of IBD must be faced exploiting an integrated and multilevel approach, ranging from genes, transcripts and proteins to pathways altered in affected tissues, and carefully considering their regulatory mechanisms, which may intervene in the pathology onset. It is also crucial to have a knowledge base about the symbiotic bacteria that are hosted in the human gut. To date, much data exist regarding IBD and human commensal bacteria, but this information is sparse in literature and no free resource provides a homogeneously and rationally integrated view of biomolecular data related to these pathologies.MethodsHuman genes altered in IBD have been collected from literature, paying particular interest for the immune system alterations prompted by the interaction with the gut microbiome. This process has been performed manually to assure the reliability of collected data. Heterogeneous metadata from different sources have been automatically formatted and integrated in order to enrich information about these altered genes. A user-friendly web interface has been created for easy access to structured data. Tools such as gene clustering coefficients, all-pairs shortest paths and pathway lengths calculation have been developed to provide data analysis support. Moreover, the implemented resource is compliant to the Galaxy framework, allowing the collected data to be exploited in the context of high throughput bioinformatics analysis.ResultsTo fill the lack of a reference resource for 'omics' science analysis in the context of IBD, we developed the IBDsite (available at http://www.itb.cnr.it/ibd), a disease-oriented platform, which collects data related to biomolecular mechanisms involved in the IBD onset. The resource provides a section devoted to human genes identified as altered in IBD, which can be queried at different biomolecular levels and visualised in gene-centred report pages. Furthermore, the system presents information related to the gut microbiota involved in IBD affected patients. The IBDsite is compliant with all Galaxy installations (in particular, it can be accessed from our custom version of Galaxy, http://www.itb.cnr.it/galaxy), in order to facilitate high-throughput data integration and to enable evaluations of the genomic basis of these diseases, complementing the tools embedded in the IBDsite.ConclusionsLots of sparse data exist concerning IBD studies, but no on-line resource homogeneously and rationally integrate and collect them. The IBDsite is an attempt to group available information regarding human genes and microbial aspects related to IBD, by means of a multilevel mining tool. Moreover, it constitutes a knowledge base to filter, annotate and understand new experimental data in order to formulate new scientific hypotheses, thanks to the possibility of integrating genomics aspects by employing the Galaxy framework. Discussed use-cases demonstrate that the developed system is useful to infer not trivial knowledge from the existing widespread data or from novel experiments.

Dataset Information

High-Throughput Identification of the Plasma Proteomic Signature of Inflammatory Bowel Disease.

Publications

High-Throughput Identification of the Plasma Proteomic Signature of Inflammatory Bowel Disease.

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