4.6 Article

Evaluation of Pathway Activation for a Single Sample Toward Inflammatory Bowel Disease Classification

Journal

FRONTIERS IN GENETICS
Volume 10, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fgene.2019.01401

Keywords

similar complex diseases; pathway activation; single sample; inflammatory bowel disease; pathway biomarkers

Funding

  1. National Natural Science Foundation of China [61832019, 61702054]
  2. 111 Project [B18059]
  3. Hunan Provincial Innovation Foundation For Postgraduate [CX20190123]
  4. Hunan Provincial Natural Science Foundation of China [2018JJ3568]

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Since similar complex diseases are much alike in clinical symptoms, patients are easily misdiagnosed and mistreated. It is crucial to accurately predict the disease status and identify markers with high sensitivity and specificity for classifying similar complex diseases. Many approaches incorporating network information have been put forward to predict outcomes, but they are not robust because of their low reproducibility. Several pathway-based methods are robust and functionally interpretable. However, few methods characterize the disease-specific states of single samples from the perspective of pathways. In this study, we propose a novel framework, Pathway Activation for Single Sample (PASS), which utilizes the pathway information in a single sample way to better recognize the differences between two similar complex diseases. PASS can mainly be divided into two parts: for each pathway, the extent of perturbation of edges and the statistic difference of genes caused by a single disease sample are quantified; then, a novel method, named as an AUCpath, is applied to evaluate the pathway activation for single samples from the perspective of genes and their interactions. We have applied PASS to two main types of inflammatory bowel disease (IBD) and widely verified the characteristics of PASS. For a new patient, PASS features can be used as the indicators or potential pathway biomarkers to precisely diagnose complex diseases, discover significant features with interpretability and explore changes in the biological mechanisms of diseases.

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