Combining many techniques is key to systems biology. Credit: BEYOND GENOMICS

Beyond Genomics in Waltham, Massachusetts, is taking a broad view for target validation — its approach hinges on systems biology. The company first characterizes potential targets within their normal biochemical pathways. “We measure cells, tissues and body fluids at multiple bioanalytical levels, including transcript, protein, and endogenous metabolite and enzyme product,” says Aram Adourian, the company's senior director of advanced technologies and strategic development.

It then compares these profiles with similar profiles from disease states, and correlates features of the profile with the disease in question using pattern-recognition algorithms and bioinformatics techniques. The result is a set of potential targets, which can then be perturbed by RNAi or transgenics, for example. The subsequent biological changes are monitored by the same systems-biology approach.

As a target-validation tool, systems biology is “a truly exciting method for illuminating causative relations between target modulation and effects on disease”, says Adourian. By learning more about the biological pathways in which the target is involved, it is possible to predict the potential toxicity of perturbing its normal function, he says.

Adourian believes that an integrative approach to target validation is more likely to yield the highest-quality targets: “One ultimately needs to examine the system as a whole, with its interacting networks and components of genes, proteins, metabolites and other molecules, to begin to assemble a unified and contextualized perspective on the role, function and relevance of a potential target.”

Another firm taking a wide view of target validation is MDS Proteomics in Toronto, Canada, which uses bioinformatics, gene-expression information, high-throughput protein analysis and protein-pathway biology to identify prospective targets and gain all-round evidence of their cellular role.