title: deGPS is a powerful tool for detecting differential expression in RNA-sequencing studies.
abstract: BACKGROUND
  The advent of the NGS technologies has permitted profiling of whole-genome transcriptomes (i.e., RNA-Seq) at unprecedented speed and very low cost. RNA-Seq provides a far more precise measurement of transcript levels and their isoforms compared to other methods such as microarrays. A fundamental goal of RNA-Seq is to better identify expression changes between different biological or disease conditions. However, existing methods for detecting differential expression from RNA-Seq count data have not been comprehensively evaluated in large-scale RNA-Seq datasets. Many of them suffer from inflation of type I error and failure in controlling false discovery rate especially in the presence of abnormal high sequence read counts in RNA-Seq experiments.
  
  
  RESULTS
  To address these challenges, we propose a powerful and robust tool, termed deGPS, for detecting differential expression in RNA-Seq data. This framework contains new normalization methods based on generalized Poisson distribution modeling sequence count data, followed by permutation-based differential expression tests. We systematically evaluated our new tool in simulated datasets from several large-scale TCGA RNA-Seq projects, unbiased benchmark data from compcodeR package, and real RNA-Seq data from the development transcriptome of Drosophila. deGPS can precisely control type I error and false discovery rate for the detection of differential expression and is robust in the presence of abnormal high sequence read counts in RNA-Seq experiments.
  
  
  CONCLUSIONS
  Software implementing our deGPS was released within an R package with parallel computations ( https://github.com/LL-LAB-MCW/deGPS ). deGPS is a powerful and robust tool for data normalization and detecting different expression in RNA-Seq experiments. Beyond RNA-Seq, deGPS has the potential to significantly enhance future data analysis efforts from many other high-throughput platforms such as ChIP-Seq, MBD-Seq and RIP-Seq.
authors.affiliation: Department of Statistics and Finance, University of Science and Technology of China, Hefei, Anhui, 230026, China. chenchu@mcw.edu.|Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA. chenchu@mcw.edu.|Department of Gynecologic Oncology, The Affiliated Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310029, China. chenchu@mcw.edu.
authors.forename: Chen
authors.initials: C
authors.lastname: Chu
authors.affiliation: Department of Statistics and Finance, University of Science and Technology of China, Hefei, Anhui, 230026, China. zbfang@ustc.edu.cn.
authors.forename: Zhaoben
authors.initials: Z
authors.lastname: Fang
authors.affiliation: Department of Statistics and Finance, University of Science and Technology of China, Hefei, Anhui, 230026, China. xing.hua@nih.gov.|Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA. xing.hua@nih.gov.
authors.forename: Xing
authors.initials: X
authors.lastname: Hua
authors.affiliation: Department of Statistics and Finance, University of Science and Technology of China, Hefei, Anhui, 230026, China. ynyang@ustc.edu.cn.
authors.forename: Yaning
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Division of Respiratory Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, China. georgechen100@gmail.com.
authors.forename: Enguo
authors.initials: E
authors.lastname: Chen
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA. cowley@mcw.edu.
authors.forename: Allen W
authors.initials: AW
authors.lastname: Cowley
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA. mliang@mcw.edu.
authors.forename: Mingyu
authors.initials: M
authors.lastname: Liang
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA. pliu@mcw.edu.|Division of Respiratory Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310058, China. pliu@mcw.edu.|Institute for Translational Medicine, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310029, China. pliu@mcw.edu.
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Gynecologic Oncology, The Affiliated Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310029, China. yanlu76@zju.edu.cn.|Institute for Translational Medicine, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310029, China. yanlu76@zju.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
mesh_terms: D019295:Computational Biology / Q000379:methods; D030541:Databases, Genetic; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D006801:Humans; D016012:Poisson Distribution; D017423:Sequence Analysis, RNA / Q000379:methods*; D012984:Software; D059467:Transcriptome