Th e human genome can be investigated from two diff erent angles that consist of either determining its make up or measuring its output. Sequence variation can be detected using, for instance, single nucleotide polymorphism (SNP) chips, which permit the identifi cation of common polymorphisms or rare mutations associated with diseases. Hundreds of thousands of SNPs can be typed using these platforms, yielding a genome-wide, hypothesis-free scan of genetic associations for a given phenotype of interest. Many such genome-wide association studies (often referred to as GWAS) have been published in recent years, a number of them investigating the genetic underpinning of immune-related diseases [1] . Notably, such studies have been useful to pinpoint genes and pathways that may be involved in the pathogenesis of Figure 1 . Blood is the pipeline of the immune system. Transcriptional profi ling in the blood consists of measuring RNA abundance in circulating nucleated cells. Changes in transcript abundance can result from exposure to host or pathogen-derived immunogenic factors (for example, pathogen-derived molecular patterns activating specialized pattern recognition receptors expressed at the surface of leukocytes) and/or changes in relative cellular composition (for example, infl ux of immature neutrophils occurring in response to bacterial infection). The main blood leukocyte populations circulating in the blood are represented in this fi gure. Each cell type has a specialized function. Eosinophils, basophils and neutrophils are innate immune eff ectors playing a key role in defense against pathogens. T lymphocytes are the mediators of the adaptive cellular immune response. Antibody producing B lymphocytes (plasma cells) are key eff ectors of the humoral immune response. Monocytes, dendritic cells and B lymphocytes present antigens to T lymphocytes and play a central role in the development of the adaptive immune response. Blood leukocytes can be exposed in the circulation to factors released systemically from tissues where pathogenic processes take place. In addition, leukocytes will cross the endothelial barrier to reach local sites of infl ammation. Dendritic cells exposed to infl ammatory factors in tissues will be transported via the lymphatic system and reach lymph nodes via the aff erent lymphatic vessels. These dendritic cells will encounter naïve T cells that are transported to the lymph node via high endothelial venules. 'Educated' T cells will then exit the lymph node via eff erent lymph vessels that collect in the thoracic lymph duct, which in turn connects to the subclavian vein, at which point these T cells rejoin the blood circulation. [2] . Associations between common genetic variants and resistance to infection have also been reported [3, 4] . However, parameters measured by this approach are determined by heredity and will not change throughout the life of an individual. Th is is in contrast to transcript abundance, which is the parameter measured by the second genome-wide profi ling approach. Transcriptional activity is largely dependent on environmental factors and, as a result, RNA abundance will change dynamically over time. For instance, sets of transcripts may be induced in response to an infectious challenge and return to baseline levels following pathogen clearance. Dynamic changes in the cellular make up of a tissue will also eff ect changes in transcript abundance that will be measured on a genome-wide scale.