Changing paradigm through a genome-based approach to clinical and basic immunology

Excerpt

Genomics or, in other words, genome-based biology offers an entirely new prospective on strategies applicable to the study of distinct physio-pathological conditions through a "discovery-driven" approach that may complement traditional "hypothesis-driven" scientific thinking [1‐3]. Indeed, analysis of genomic variation at the DNA level and functional genomics that addresses transcriptional variations of biological material have been extensively used by bio-scientists to study distinct pathological conditions and this trend has spread, more recently to applications in basic and clinical immunology [4‐9]. This shift in paradigm in the study of biology and, for the purpose of this Commentary, in immunology may very well be suitable for the understanding of immune regulation in sickness and in health which represents a particularly complicated biological matter due do the extreme versatility of the immune system in adaptation to environmental changes. The study of immune regulation in response to pathogen invasion, presence of malignant or allogeneic tissue and, in some cases, toward normal autologous tissue may require global approaches that could study in parallel the behavior of whole-systems. In fact, the study of single immunological parameters has, so far, failed to unlock several questions related to the immune-system complexity. This may be particularly true for tumor immunology that is a compound field in which the dynamic heterogeneity of cancer cells [10] supplements the complexity of polymorphic variation and epigenetic adaptation characteristic of human immunology [11]. In fact, new tools have been developed that allow a global vision of genetic processes in parallel at various levels that encompass genetic variation (single nucleotide polymorphism analysis), epigenetic changes (i.e. methylation-detection arrays or comparative genomic hybridization that can detect gene methylation or deletion / amplification respectively) and global transcription analysis (i.e. cDNA- or oligonucleotide-based microarrays like the lympho-chip or the peptide-MHC microarrays) that combined with bio-informatics tools provide a new approach to the description of complex immunological phenomena [3, 9, 11‐14]. …