Identification of promoters and enhancers specific for inflammatory bowel disease and its subtypes

Project Information

IPEIBD

Grant agreement ID: 659505

DOI

10.3030/659505

Project terminated on 31 August 2017

EC signature date 4 March 2015

Start date 1 June 2015

End date 29 November 2017

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 212 194,80

EU contribution

€ 212 194,80

Coordinated by

KOBENHAVNS UNIVERSITET
Denmark

Periodic Reporting for period 1 - IPEIBD (Identification of promoters and enhancers specific for inflammatory bowel disease and its subtypes)

Reporting period: 2015-06-01 to 2017-05-31

Summary of the context and overall objectives of the project

Inflammatory bowel disease (IBD) is a frequent chronic intestinal disorder, with two main types: Crohn’s disease (CD) and ulcerative colitis (UC). The incidence and prevalence of IBD is highest in Europe and North America (incidence up to 24 per 100,000 person-years) and affecting up to 0.5% in the Western world. IBD is not well-understood on a molecular level, and the distinction between CD and UC is critical for prescribing correct medication and especially surgery, yet the diagnosis is challenging. As the disease is chronic, patients typically require life-long treatment, often with very expensive biological drugs, which are not always effective. As diagnoses determines treatment, molecular methods for diagnosis complementing current state of the art methods would therefore be highly beneficial, but this requires comprehensive molecular screening of many subjects.

We identified a set of biomarkers (promoters and enhancers) that could predict IBD diagnosis (Crohn’s disease, ulcerative colitis or control) with an accuracy of 85%, using targeted microfluidics qPCR, where the prediction method was trained on one group of patients and evaluated in an independent group. This shows the potential for qPCR-based diagnostics methods for IBD, complementing current histology-based approaches. More generally, our results constitute a foundation for understanding the molecular pathology and genetics of IBD.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

In this project, we have analyzed a unique emerging dataset of controlled gut biopsies taken from a large number of both UC, CD and healthy individuals (109 total) subjected to a unique RNA sequencing technology – CAGE – that can identify novel gene isoforms, transcribed enhancers and non-coding RNAs. The precise locations and activity of promoters and enhancers across the large patient population enabled us to train a classification method to predict the diagnosis of the subjects (healthy, Crohn’s disease or ulcerative colitis). This allowed us to identify a set of biomarkers, mentioned above, that have potential for use in the clinic for more accurate diagnosis of the disease.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

This biomarker set is potentially applicable in the clinic as a way of increasing the accuracy of diagnosis and thus enable accurate medication – a cornerstone of precision medicine. It has commercial value for a wider use and we are in the process of looking for interested parties. A patent has been submitted for this set and it has commercial value for a wider use.