title: Multiple-omic data analysis of Klebsiella pneumoniae MGH 78578 reveals its transcriptional architecture and regulatory features.
abstract: BACKGROUND
  The increasing number of infections caused by strains of Klebsiella pneumoniae that are resistant to multiple antibiotics has developed into a major medical problem worldwide. The development of next-generation sequencing technologies now permits rapid sequencing of many K. pneumoniae isolates, but sequence information alone does not provide important structural and operational information for its genome.
  
  
  RESULTS
  Here we take a systems biology approach to annotate the K. pneumoniae MGH 78578 genome at the structural and operational levels. Through the acquisition and simultaneous analysis of multiple sample-matched -omics data sets from two growth conditions, we detected 2677, 1227, and 1066 binding sites for RNA polymerase, RpoD, and RpoS, respectively, 3660 RNA polymerase-guided transcript segments, and 3585 transcription start sites throughout the genome. Moreover, analysis of the transcription start site data identified 83 probable leaderless mRNAs, while analysis of unannotated transcripts suggested the presence of 119 putative open reading frames, 15 small RNAs, and 185 antisense transcripts that are not currently annotated.
  
  
  CONCLUSIONS
  These findings highlight the strengths of systems biology approaches to the refinement of sequence-based annotations, and to provide new insight into fundamental genome-level biology for this important human pathogen.
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Joo-Hyun
authors.initials: JH
authors.lastname: Seo
authors.forename: Jay Sung-Joong
authors.initials: JS
authors.lastname: Hong
authors.forename: Donghyuk
authors.initials: D
authors.lastname: Kim
authors.forename: Byung-Kwan
authors.initials: BK
authors.lastname: Cho
authors.forename: Tzu-Wen
authors.initials: TW
authors.lastname: Huang
authors.forename: Shih-Feng
authors.initials: SF
authors.lastname: Tsai
authors.forename: Bernhard O
authors.initials: BO
authors.lastname: Palsson
authors.forename: Pep
authors.initials: P
authors.lastname: Charusanti
mesh_terms: D012321:DNA-Directed RNA Polymerases / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks; D016680:Genome, Bacterial; D007711:Klebsiella pneumoniae / Q000235:genetics*; D058977:Molecular Sequence Annotation; D016366:Open Reading Frames; D016372:RNA, Antisense; D058727:RNA, Small Untranslated; D017422:Sequence Analysis, DNA; D012808:Sigma Factor / Q000235:genetics; D049490:Systems Biology; D024363:Transcription Initiation Site; D014158:Transcription, Genetic
chemical_list: D016372:RNA, Antisense; D058727:RNA, Small Untranslated; D012808:Sigma Factor; D012321:DNA-Directed RNA Polymerases