**3. Uses of gene expression profiling**

Quantification of the transcriptome has been a useful mechanism for both discovering and defining mechanisms of pathogenesis in ALS (Cox et al 2010; Ferraiuolo et al 2007; Kirby et al 2005; Kirby et al 2011). In particular lists of differentially expressed genes can be usefully converted to functional 'themes' by an enrichment analysis (Hosack et al 2003). Various categorisations exist, including the gene ontology (GO) and Kyoto encyclopaedia of genes and genomes (KEGG), which classify genes according to molecular function, biological process, cellular component or a known biological pathway.

A frequent application of gene expression profiling has been the development of putative biomarkers via a supervised classification approach (Booij et al 2011; Nagasaka et al 2005; Scherzer et al 2007). The large number of targets quantified simultaneously by gene expression profiling is essential for biomarker discovery, as it allows an unbiased survey of the most informative RNA transcripts. A reliable biomarker(s) for defining pathogenesis and prognosis in ALS has yet to be established, though gene expression profiling is one of the methodologies currently being used to establish an ALS biomarker(s).
