title: Identification of novel predictor classifiers for inflammatory bowel disease by gene expression profiling.
abstract: BACKGROUND
  Improvement of patient quality of life is the ultimate goal of biomedical research, particularly when dealing with complex, chronic and debilitating conditions such as inflammatory bowel disease (IBD). This is largely dependent on receiving an accurate and rapid diagnose, an effective treatment and in the prediction and prevention of side effects and complications. The low sensitivity and specificity of current markers burden their general use in the clinical practice. New biomarkers with accurate predictive ability are needed to achieve a personalized approach that take the inter-individual differences into consideration.
  
  
  METHODS
  We performed a high throughput approach using microarray gene expression profiling of colon pinch biopsies from IBD patients to identify predictive transcriptional signatures associated with intestinal inflammation, differential diagnosis (Crohn's disease or ulcerative colitis), response to glucocorticoids (resistance and dependence) or prognosis (need for surgery). Class prediction was performed with self-validating Prophet software package.
  
  
  RESULTS
  Transcriptional profiling divided patients in two subgroups that associated with degree of inflammation. Class predictors were identified with predictive accuracy ranging from 67 to 100%. The expression accuracy was confirmed by real time-PCR quantification. Functional analysis of the predictor genes showed that they play a role in immune responses to bacteria (PTN, OLFM4 and LILRA2), autophagy and endocytocis processes (ATG16L1, DNAJC6, VPS26B, RABGEF1, ITSN1 and TMEM127) and glucocorticoid receptor degradation (STS and MMD2).
  
  
  CONCLUSIONS
  We conclude that using analytical algorithms for class prediction discovery can be useful to uncover gene expression profiles and identify classifier genes with potential stratification utility of IBD patients, a major step towards personalized therapy.
authors.affiliation: The William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, London, United Kingdom.
authors.forename: Trinidad
authors.initials: T
authors.lastname: Montero-Meléndez
authors.forename: Xavier
authors.initials: X
authors.lastname: Llor
authors.forename: Esther
authors.initials: E
authors.lastname: García-Planella
authors.forename: Mauro
authors.initials: M
authors.lastname: Perretti
authors.forename: Antonio
authors.initials: A
authors.lastname: Suárez
mesh_terms: D003093:Colitis, Ulcerative / Q000145:classification / Q000235:genetics; D003424:Crohn Disease / Q000145:classification / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics; D015212:Inflammatory Bowel Diseases / Q000145:classification* / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results