title: SMAP: a streamlined methylation analysis pipeline for bisulfite sequencing.
abstract: BACKGROUND
  DNA methylation has important roles in the regulation of gene expression and cellular specification. Reduced representation bisulfite sequencing (RRBS) has prevailed in methylation studies due to its cost-effectiveness and single-base resolution. The rapid accumulation of RRBS data demands well designed analytical tools.
  
  
  RESULTS
  To streamline the data processing of DNA methylation from multiple RRBS samples, we present a flexible pipeline named SMAP, whose features include: (i) handling of single-and/or paired-end diverse bisulfite sequencing data with reduced false-positive rates in differentially methylated regions; (ii) detection of allele-specific methylation events with improved algorithms; (iii) a built-in pipeline for detection of novel single nucleotide polymorphisms (SNPs); (iv) support of multiple user-defined restriction enzymes; (v) conduction of all methylation analyses in a single-step operation when well configured.
  
  
  CONCLUSIONS
  Simulation and experimental data validated the high accuracy of SMAP for SNP detection and methylation identification. Most analyses required in methylation studies (such as estimation of methylation levels, differentially methylated cytosine groups, and allele-specific methylation regions) can be executed readily with SMAP. All raw data from diverse samples could be processed in parallel and 'packetized' streams. A simple user guide to the methylation applications is also provided.
authors.affiliation: Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark ; BGI Co Ltd, Shenzhen, 518083 China ; Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Shengjie
authors.initials: S
authors.lastname: Gao
authors.affiliation: BGI Co Ltd, Shenzhen, 518083 China ; School of Computer Science, National University of Defense Technology, Changsha, 410073 China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zou
authors.affiliation: BGI Co Ltd, Shenzhen, 518083 China ; Genomic Biology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors.forename: Likai
authors.initials: L
authors.lastname: Mao
authors.affiliation: BGI Co Ltd, Shenzhen, 518083 China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: BGI Co Ltd, Shenzhen, 518083 China ; Department of Computer Science, City University of Hong Kong, Hong Kong, 999077 China.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Jia
authors.affiliation: Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Huang
authors.affiliation: BGI Co Ltd, Shenzhen, 518083 China.
authors.forename: Shancen
authors.initials: S
authors.lastname: Zhao
authors.affiliation: BGI Co Ltd, Shenzhen, 518083 China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, China.
authors.forename: Song
authors.initials: S
authors.lastname: Wu
authors.affiliation: BGI Co Ltd, Shenzhen, 518083 China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Li
authors.affiliation: Electronic Engineering College, Naval Engineering University, Jiefang Avenue #717, Wuhan, 430033 China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xia
authors.affiliation: BGI Co Ltd, Shenzhen, 518083 China.
authors.forename: Huafeng
authors.initials: H
authors.lastname: Chen
authors.affiliation: BGI Co Ltd, Shenzhen, 518083 China.
authors.forename: Maoshan
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Torben F
authors.initials: TF
authors.lastname: Ørntoft
authors.affiliation: BGI Co Ltd, Shenzhen, 518083 China ; Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Bolund
authors.affiliation: Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Karina D
authors.initials: KD
authors.lastname: Sørensen
mesh_terms: D000465:Algorithms; D019175:DNA Methylation; D020641:Polymorphism, Single Nucleotide; D013447:Sulfites / Q000737:chemistry*
chemical_list: D013447:Sulfites; C042345:hydrogen sulfite
keywords: Allele-specific DNA methylation (ASM); Differentially methylated region (DMR); Reduced representation bisulfite sequencing (RRBS)