title: From experimental design to functional gene networks: DNA microarray contribution to skin ageing research.
abstract: There is no doubt that the DNA microarray-based technology contributed to increase our knowledge of a wide range of processes. However, integrating genes into functional networks, rather than terms describing generic characteristics, remains an important challenge. The highly context-dependent function of a given gene and feedback mechanisms complexify greatly the interpretation of the data. Moreover, it is difficult to determine whether changes in gene expression are the result or the cause of pathologies or physiological events. In both cases, the difficulty relies on the involvement of processes that, at an early stage, can be protective and later on, deleterious because of their runaway. Each individual cell has its own transcription profile that determines its behaviour and its relationships with its neighbours. This is particularly true when a mechanism such as cell cycle is concerned. Another issue concerns the analyses from samples of different donors. Whereas the statistical tools lead to determine common features among groups, they tend to smooth the overall data and consequently, the selected values represent the 'tip of the iceberg'. There is a significant overlap in the set of genes identified in the different studies on skin ageing processes described in the present review. The reason of this overlap is because most of these genes belong to the basic machinery controlling cell growth and arrest. To get a more full picture of these processes, a hard work has still to be done to determine the precise mechanisms conferring the cell type specificity of ageing. Integrative biology applied to the huge amount of existing microarray data should fulfil gaps, through the characterization of additional actors accounting for the activation of specific signalling pathways at crossing points. Furthermore, computational tools have to be developed taking into account that expression values among similar groups may not vary 'by chance' but may reflect, along with other subtle changes, specific features of one given donor. Through a better stratification, these tools will allow to recover genes from the 'bottom of the iceberg'. Identifying these genes should contribute to understand how skin ages among individuals, thus paving the way for personalized skin care.
authors: UMR 7259 (NICN) CNRS - Aix-Marseille Université, Faculté de Médecine Secteur Nord, CS80011, 51 Bd Pierre Dramard, Marseille CEDEX 15, 13344, France.
authors: P D
authors: PD
authors: Benech
authors: A
authors: A
authors: Patatian
mesh_terms: D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D019295:Computational Biology / Q000379:methods; D053263:Gene Regulatory Networks / Q000235:genetics / Q000502:physiology*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D012313:RNA / Q000235:genetics; D015595:Skin Aging / Q000235:genetics / Q000502:physiology*
chemical_list: D012313:RNA
keywords: ageing; functional genomics; gene expression; senescence