The hepatic transcriptome in human liver disease

The sequencing of the human and other genomes has heralded the age of functional genomics. Although an invaluable resource in understanding human biology and disease, the frequent lack of sequence correlation with a defined tissue or disease phenotype has led to the genomic sequence databases being huge reservoirs of knowledge that mostly aid but do not direct research. We have the start of the map for human disease but only limited understanding of how it unfolds. Moreover, this genomic "gene map" is invariant across an entire organism and it is the expression of messenger RNA (mRNA) gene transcripts and resultant protein expression that defines normal molecular homeostasis and pathobiology. Functional genomics studies attempt to correlate gene mRNA transcript expression with a characterised phenotype thereby inferring function.The entire mRNA transcript pool within a cell or tissue has been labelled the transcriptome [1-3]. Similarly, the proteome refers to the entire protein pool. Understanding the regulation and expression of transcriptomes or proteomes in a disease specific context is pivotal to understanding human disease. Further, although proteins are the mediators of molecular pathobiology proteome expression is ultimately controlled by the transcriptome. Approaches aimed at understanding the relationship between mRNA and protein expression are complementary and important in understanding disease [1,2]. No single approach or methodology to examine the transcriptome is "best" or "correct" and one of the central goals of this review is to highlight the benefits and deficiencies of many current approaches being utilized to examine transciptomes (Table 1). Additionally, understanding the relationship between the transcriptome and proteome is essential in interpreting functional genomic studies.Organ specific research has lagged behind the understanding of general biological processes. However, most human disease is defined by unique changes to organ specific tr