Skip to main content
Article thumbnail
Location of Repository

A Novel Dynamic Impact Approach (DIA) for Functional Analysis of Time-Course Omics Studies: Validation Using the Bovine Mammary Transcriptome

By Massimo Bionaz, Kathiravan Periasamy, Sandra L. Rodriguez-Zas, Walter L. Hurley and Juan J. Loor


The overrepresented approach (ORA) is the most widely-accepted method for functional analysis of microarray datasets. The ORA is computationally-efficient and robust; however, it suffers from the inability of comparing results from multiple gene lists particularly with time-course experiments or those involving multiple treatments. To overcome such limitation a novel method termed Dynamic Impact Approach (DIA) is proposed. The DIA provides an estimate of the biological impact of the experimental conditions and the direction of the impact. The impact is obtained by combining the proportion of differentially expressed genes (DEG) with the log2 mean fold change and mean –log P-value of genes associated with the biological term. The direction of the impact is calculated as the difference of the impact of up-regulated DEG and down-regulated DEG associated with the biological term. The DIA was validated using microarray data from a time-course experiment of bovine mammary gland across the lactation cycle. Several annotation databases were analyzed with DIA and compared to the same analysis performed by the ORA. The DIA highlighted that during lactation both BTA6 and BTA14 were the most impacted chromosomes; among Uniprot tissues those related with lactating mammary gland were the most positively-impacted; within KEGG pathways ‘Galactose metabolism’ and several metabolism categories related to lipid synthesis were among the most impacted and induced; within Gene Ontology “lactose biosynthesis” among Biological processes and “Lactose synthase activity” and “Stearoyl-CoA 9-desaturase activity” among Molecular processes were the most impacted and induced. With the exception of the terms ‘Milk’, ‘Milk protein’ and ‘Mammary gland’ among Uniprot tissues and SP_PIR_Keyword, the use of ORA failed to capture as significantly-enriched (i.e., biologically relevant) any term known to be associated with lactating mammary gland. Results indicate the DIA is a biologically-sound approach for analysis of time-course experiments. This tool represents an alternative to ORA for functional analysis

Topics: Research Article
Publisher: Public Library of Science
OAI identifier:
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles


    1. (2009). A functional genomics approach to evaluate candidate genes located in a QTL interval for milk production traits on BTA6.
    2. (1999). A genome scan for QTL influencing milk production and health traits in dairy cattle.
    3. (2002). A genome scan for quantitative trait loci affecting milk production in Norwegian dairy cattle.
    4. (1998). A QTL with major effect on milk yield and composition maps to bovine chromosome 14.
    5. (2007). A systems biology approach for pathway level analysis.
    6. (2009). Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists.
    7. (1976). Clathrin: a unique protein associated with intracellular transfer of membrane by coated vesicles.
    8. (2003). Cloned transgenic cattle produce milk with higher levels of beta-casein and kappacasein.
    9. (2006). Co-expression of bovine statherin gene with casein gene /i CSN1S1. Animal Science Papers and Reports
    10. (2010). Confirmation and refinement of a QTL on BTA5 affecting milk production traits in the Fleckvieh dual purpose cattle breed.
    11. (1995). Controlling the False Discovery Rate – a Practical and Powerful Approach to Multiple Testing.
    12. (2007). Enrichment analysis in highthroughput genomics - accounting for dependency in the NULL.
    13. (2006). Evolution of the mammary gland from the innate immune system?
    14. (2011). Gene networks driving bovine mammary protein synthesis during the lactation cycle.
    15. (2008). Gene networks driving bovine milk fat synthesis during the lactation cycle.
    16. (2008). Genome assembly anchored QTL map of bovine chromosome 14.
    17. (2010). GO-Bayes: Gene Ontology-based overrepresentation analysis using a Bayesian approach.
    18. (2005). Identification of a missense mutation in the bovine ABCG2 gene with a major effect on the QTL on chromosome 6 affecting milk yield and composition in Holstein cattle.
    19. (2004). Increased milk yield in transgenic mice expressing insulin-like growth factor 1.
    20. (2011). Invited review: quantitative trait nucleotide determination in the era of genomic selection.
    21. (2002). Lactational performance of first-parity transgenic gilts expressing bovine alphalactalbumin in their milk.
    22. (2009). Lactose synthase components in milk: concentrations of alpha-lactalbumin and beta1,4-galactosyltransferase in milk of cows from several breeds at various stages of lactation.
    23. (2006). Major advances associated with the biosynthesis of milk.
    24. (2005). Mammary specific transgenic over-expression of insulin-like growth factor-I (IGF-I) increases pig milk IGF-I and IGF binding proteins, with no effect on milk composition or yield.
    25. (1995). Mapping quantitative trait loci controlling milk production in dairy cattle by exploiting progeny testing.
    26. (1984). Metabolites of nucleic acids in bovine milk.
    27. (1999). Mouse mammary gland xanthine oxidoreductase: purification, characterization, and regulation.
    28. (2009). Peroxisome proliferator-activated receptor-gamma activation and long-chain fatty acids alter lipogenic gene networks in bovine mammary epithelial cells to various extents.
    29. (2002). Positional candidate cloning of a QTL in dairy cattle: identification of a missense mutation in the bovine DGAT1 gene with major effect on milk yield and composition.
    30. (1998). Production of bovine alpha-lactalbumin in the milk of transgenic pigs.
    31. (2003). Quantitative trait loci affecting milk production traits in Finnish Ayrshire dairy cattle.
    32. (2004). Quantitative trait loci mapping in dairy cattle: review and meta-analysis.
    33. (2001). Roads taken by milk proteins in mammary epithelial cells.
    34. (2003). Search for pleiotropic QTL on chromosome BTA6 affecting yield traits of milk production.
    35. (2001). Short communication: effects of increased expression of alpha-lactalbumin in transgenic mice on milk yield and pup growth.
    36. (2009). Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources.
    37. (2009). The concordance test emerges as a powerful tool for identifying quantitative trait nucleotides: lessons from BTA6 milk yield QTL.
    38. (1972). The effect of intravenous infusions of sterculic acid on milk fat synthesis.
    39. (2002). The housekeeping gene xanthine oxidoreductase is necessary for milk fat droplet enveloping and secretion: gene sharing in the lactating mammary gland.
    40. (2008). The life cycle of a transport vesicle.
    41. (1999). The majority of clathrin coated vesicles from lactating rabbit mammary gland arises from the secretory pathway.
    42. (2001). Transgenic alteration of sow milk to improve piglet growth and health.
    43. (2000). Transport of milk constituents by the mammary gland.

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.