title: Synergizing genomic analysis with biological knowledge to identify and validate novel genes in pancreatic development.
abstract: OBJECTIVE
  This study investigated the utility of advanced computational techniques to large-scale genome-based data to identify novel genes that govern murine pancreatic development.
  
  
  METHODS
  An expression data set for mouse pancreatic development was complemented with high-throughput data analyzer to identify and prioritize novel genes. Quantitative real-time polymerase chain reaction, in situ hybridization, and immunohistochemistry were used to validate selected genes.
  
  
  RESULTS
  Four new genes whose roles in the development of murine pancreas have not previously been established were identified: cystathionine β-synthase (Cbs), Meis homeobox 1, growth factor independent 1, and aldehyde dehydrogenase 18 family, member A1. Their temporal expression during development was documented. Cbs was localized in the cytoplasm of the tip cells of the epithelial chords of the undifferentiated progenitor cells at E12.5 and was coexpressed with the pancreatic and duodenal homeobox 1 and pancreas-specific transcription factor, 1a-positive cells. In the adult pancreas, Cbs was localized primarily within the acinar compartment.
  
  
  CONCLUSIONS
  In silico analysis of high-throughput microarray data in combination with background knowledge about genes provides an additional reliable method of identifying novel genes. To our knowledge, the expression and localization of Cbs have not been previously documented during mouse pancreatic development.
authors.affiliation: Barbara Davis Center for Childhood Diabetes, School of Medicine, University of Colorado Denver, Aurora, CO 80045, USA. suparna.sarkar@ucdenver.edu
authors.forename: Suparna A
authors.initials: SA
authors.lastname: Sarkar
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Lee
authors.forename: Hannah
authors.initials: H
authors.lastname: Tipney
authors.forename: Anis
authors.initials: A
authors.lastname: Karimpour-Fard
authors.forename: Jason D
authors.initials: JD
authors.lastname: Dinella
authors.forename: Kirstine
authors.initials: K
authors.lastname: Juhl
authors.forename: Jay A
authors.initials: JA
authors.lastname: Walters
authors.forename: John C
authors.initials: JC
authors.lastname: Hutton
authors.forename: Lawrence E
authors.initials: LE
authors.lastname: Hunter
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D019295:Computational Biology; D003541:Cystathionine beta-Synthase / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D030541:Databases, Genetic; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D023281:Genomics / Q000379:methods; D005865:Gestational Age; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D009024:Morphogenesis / Q000235:genetics*; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010179:Pancreas / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C079873:Gfi1 protein, mouse; D018398:Homeodomain Proteins; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D000444:Aldehyde Dehydrogenase; D003541:Cystathionine beta-Synthase