title: Explore Small Molecule-induced Genome-wide Transcriptional Profiles for Novel Inflammatory Bowel Disease Drug.
abstract: Inflammatory Bowel Disease (IBD) is a chronic and relapsing disorder, which affects millions people worldwide. Current drug options cannot cure the disease and may cause severe side effects. We developed a systematic framework to identify novel IBD drugs exploiting millions of genomic signatures for chemical compounds. Specifically, we searched all FDA-approved drugs for candidates that share similar genomic profiles with IBD. In the evaluation experiments, our approach ranked approved IBD drugs averagely within top 26% among 858 candidates, significantly outperforming a state-of-art genomics-based drug repositioning method (p-value < e-8). Our approach also achieved significantly higher average precision than the state-of-art approach in predicting potential IBD drugs from clinical trials (0.072 vs. 0.043, p<0.1) and off-label IBD drugs (0.198 vs. 0.138, p<0.1). Furthermore, we found evidences supporting the therapeutic potential of the top-ranked drugs, such as Naloxone, in literature and through analyzing target genes and pathways.
authors: Department of Electrical Engineering and Computer Science, School of Engineering, Case Western Reserve University, Cleveland, Ohio, USA.
authors: Xiaoshu
authors: X
authors: Cai
authors: Department of Epidemiology & Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
authors: Yang
authors: Y
authors: Chen
authors: Department of Epidemiology & Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
authors: Zhen
authors: Z
authors: Gao
authors: Department of Epidemiology & Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
authors: Rong
authors: R
authors: Xu