Progress in gene expression profiling by the introduction of metagenes

摘要

Identification of toxic mechanisms by test compound-induced gene expression alterations is one of the major topics in current toxicological research (Ellinger-Ziegelbauer et al. 2008; Yamauchi et al. 2011; Bolt et al. 2010; Shimada et al. 2010; Adler et al. 2011; Heise et al. 2012). Also, a great deal of effort has been invested to optimize cell systems for gene array analyses in vitro (Godoy et al. 2009, 2010a, b; Zellmer et al. 2010; Hoehme et al. 2010). Recently, Schmidt and colleagues have introduced a technique that substantially facilitated the understanding and biological interpretation of complex gene expression profiles (Schmidt et al. 2008, 2009a, b, 2011, 2012): the metagenes of biological motifs. The authors observed sets of highly correlated genes in breast cancer tissue. Interestingly, these sets belonged to specific biological motifs, for example the proliferation metagene or a metagene of genes associated with the oestrogen receptor. Of particular interest are the newly discovered B- and T-cell metagenes that indicate an infiltration of the tissue with immune cells. However, the presence of normal tissue can also be identified by a 'normal-like metagene'. Further studies have reported that the mechanoactivity of tumour cells (Martin et al. 2012), stem cell properties (Lee et al. 2010), glycerophospholipid profiles (Cadenas et al. 2010) and apoptosis sensitivity (Petry et al. 2010) can be reflected by specific profiles of gene expression.