title: Transcriptomic analysis of human lung development.
abstract: BACKGROUND
  Current understanding of the molecular regulation of lung development is limited and derives mostly from animal studies.
  
  
  OBJECTIVE
  To define global patterns of gene expression during human lung development.
  
  
  METHODS
  Genome-wide expression profiling was used to measure the developing lung transcriptome in RNA samples derived from 38 normal human lung tissues at 53 to 154 days post conception. Principal component analysis was used to characterize global expression variation and to identify genes and bioontologic attributes contributing to these variations. Individual gene expression patterns were verified by quantitative reverse transcriptase-polymerase chain reaction analysis.
  
  
  RESULTS
  Gene expression analysis identified attributes not previously associated with lung development, such as chemokine-immunologic processes. Lung characteristics attributes (e.g., surfactant function) were observed at an earlier-than-anticipated age. We defined a 3,223 gene developing lung characteristic subtranscriptome capable of describing a majority of the process. In gene expression space, the samples formed a time-contiguous trajectory with transition points correlating with histological stages and suggesting the existence of novel molecular substages. Induction of surfactant gene expression characterized a pseudoglandular "molecular phase" transition. Individual gene expression patterns were independently validated. We predicted the age of independent human lung transcriptome profiles with a median absolute error of 5 days, supporting the validity of the data and modeling approach.
  
  
  CONCLUSIONS
  This study extends our knowledge of key gene expression patterns and bioontologic attributes underlying early human lung developmental processes. The data also suggest the existence of molecular phases of lung development.
authors.affiliation: Children's Hospital Informatics Program, Harvard-MIT Division of Health Sciences and Technology, Boston, Massachusetts, USA.
authors.forename: Alvin T
authors.initials: AT
authors.lastname: Kho
authors.forename: Soumyaroop
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: Kelan G
authors.initials: KG
authors.lastname: Tantisira
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Carey
authors.forename: Roger
authors.initials: R
authors.lastname: Gaedigk
authors.forename: J Steven
authors.initials: JS
authors.lastname: Leeder
authors.forename: Isaac S
authors.initials: IS
authors.lastname: Kohane
authors.forename: Scott T
authors.initials: ST
authors.lastname: Weiss
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Mariani
mesh_terms: D047109:Fetal Development / Q000235:genetics*; D020869:Gene Expression Profiling; D005865:Gestational Age; D006801:Humans; D008168:Lung / Q000196:embryology*; D020411:Oligonucleotide Array Sequence Analysis; D025341:Principal Component Analysis; D011663:Pulmonary Surfactants
chemical_list: D011663:Pulmonary Surfactants