title: Large scale physiological readjustment during growth enables rapid, comprehensive and inexpensive systems analysis.
abstract: BACKGROUND
  Rapidly characterizing the operational interrelationships among all genes in a given organism is a critical bottleneck to significantly advancing our understanding of thousands of newly sequenced microbial and eukaryotic species. While evolving technologies for global profiling of transcripts, proteins, and metabolites are making it possible to comprehensively survey cellular physiology in newly sequenced organisms, these experimental techniques have not kept pace with sequencing efforts. Compounding these technological challenges is the fact that individual experiments typically only stimulate relatively small-scale cellular responses, thus requiring numerous expensive experiments to survey the operational relationships among nearly all genetic elements. Therefore, a relatively quick and inexpensive strategy for observing changes in large fractions of the genetic elements is highly desirable.
  
  
  RESULTS
  We have discovered in the model organism Halobacterium salinarum NRC-1 that batch culturing in complex medium stimulates meaningful changes in the expression of approximately two thirds of all genes. While the majority of these changes occur during transition from rapid exponential growth to the stationary phase, several transient physiological states were detected beyond what has been previously observed. In sum, integrated analysis of transcript and metabolite changes has helped uncover growth phase-associated physiologies, operational interrelationships among two thirds of all genes, specialized functions for gene family members, waves of transcription factor activities, and growth phase associated cell morphology control.
  
  
  CONCLUSIONS
  Simple laboratory culturing in complex medium can be enormously informative regarding the activities of and interrelationships among a large fraction of all genes in an organism. This also yields important baseline physiological context for designing specific perturbation experiments at different phases of growth. The integration of such growth and perturbation studies with measurements of associated environmental factor changes is a practical and economical route for the elucidation of comprehensive systems-level models of biological systems.
authors.affiliation: Institute for Systems Biology, 1441 North 34th Street, Seattle, WA 98103, USA. mtfacciotti@ucdavis.edu
authors.forename: Marc T
authors.initials: MT
authors.lastname: Facciotti
authors.forename: Wyming L
authors.initials: WL
authors.lastname: Pang
authors.forename: Fang-yin
authors.initials: FY
authors.lastname: Lo
authors.forename: Kenia
authors.initials: K
authors.lastname: Whitehead
authors.forename: Tie
authors.initials: T
authors.lastname: Koide
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Masumura
authors.forename: Min
authors.initials: M
authors.lastname: Pan
authors.forename: Amardeep
authors.initials: A
authors.lastname: Kaur
authors.forename: David J
authors.initials: DJ
authors.lastname: Larsen
authors.forename: David J
authors.initials: DJ
authors.lastname: Reiss
authors.forename: Linh
authors.initials: L
authors.lastname: Hoang
authors.forename: Ewa
authors.initials: E
authors.lastname: Kalisiak
authors.forename: Trent
authors.initials: T
authors.lastname: Northen
authors.forename: Sunia A
authors.initials: SA
authors.lastname: Trauger
authors.forename: Gary
authors.initials: G
authors.lastname: Siuzdak
authors.forename: Nitin S
authors.initials: NS
authors.lastname: Baliga
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods; D004926:Escherichia coli / Q000378:metabolism; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D019617:Halobacterium salinarum / Q000235:genetics* / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods; D008954:Models, Biological; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D013597:Systems Analysis; D049490:Systems Biology; D014158:Transcription, Genetic
chemical_list: D012333:RNA, Messenger
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