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@article{Pavlidis:2019:10.1371/journal.pcbi.1006951,
author = {Pavlidis, S and Monast, C and Loza, MJ and Branigan, P and Chung, KF and Adcock, IM and Guo, Y and Rowe, A and Baribaud, F},
doi = {10.1371/journal.pcbi.1006951},
journal = {PLoS Computational Biology},
title = {I_MDS: an inflammatory bowel disease molecular activity score to classify patients with differing disease-driving pathways and therapeutic response to anti-TNF treatment},
url = {http://dx.doi.org/10.1371/journal.pcbi.1006951},
volume = {15},
year = {2019}
}

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TY  - JOUR
AB  - Crohn's disease and ulcerative colitis are driven by both common and distinct underlying mechanisms of pathobiology. Both diseases, exhibit heterogeneity underscored by the variable clinical responses to therapeutic interventions. We aimed to identify disease-driving pathways and classify individuals into subpopulations that differ in their pathobiology and response to treatment. We applied hierarchical clustering of enrichment scores derived from gene set variation analysis of signatures representative of various immunological processes and activated cell types, to a colonic biopsy dataset that included healthy volunteers, Crohn's disease and ulcerative colitis patients. Patient stratification at baseline or after anti-TNF treatment in clinical responders and non-responders was queried. Signatures with significantly different enrichment scores were identified using a general linear model. Comparisons to healthy controls were made at baseline in all participants and then separately in responders and non-responders. Fifty-nine percent of the signatures were commonly enriched in both conditions at baseline, supporting the notion of a disease continuum within ulcerative colitis and Crohn's disease. Signatures included T cells, macrophages, neutrophil activation and poly:IC signatures, representing acute inflammation and a complex mix of potential disease-driving biology. Collectively, identification of significantly enriched signatures allowed establishment of an inflammatory bowel disease molecular activity score which uses biopsy transcriptomics as a surrogate marker to accurately track disease severity. This score separated diseased from healthy samples, enabled discrimination of clinical responders and non-responders at baseline with 100% specificity and 78.8% sensitivity, and was validated in an independent data set that showed comparable classification. Comparing responders and non-responders separately at baseline to controls, 43% and 70% of signatures were enri
AU  - Pavlidis,S
AU  - Monast,C
AU  - Loza,MJ
AU  - Branigan,P
AU  - Chung,KF
AU  - Adcock,IM
AU  - Guo,Y
AU  - Rowe,A
AU  - Baribaud,F
DO  - 10.1371/journal.pcbi.1006951
PY  - 2019///
SN  - 1553-734X
TI  - I_MDS: an inflammatory bowel disease molecular activity score to classify patients with differing disease-driving pathways and therapeutic response to anti-TNF treatment
T2  - PLoS Computational Biology
UR  - http://dx.doi.org/10.1371/journal.pcbi.1006951
UR  - https://www.ncbi.nlm.nih.gov/pubmed/31039157
UR  - http://hdl.handle.net/10044/1/69530
VL  - 15
ER  -

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