situation is not impossible, and the general goal of understanding system function is worthy. Evolution solved the problem by making systems work. A question that is relevant to the proposed Genomics: GTL facilities is, What is the best route to an understanding of these systems?

Despite the temptation to draw analogies, biological systems are not similar to electrical circuits. Electrical circuits are composed of a rather small diversity of entities, whereas biological systems are composed of a multitude of dissimilar parts, even to the point of adaptive variation in apparently common components. Given the scale and complexity of the challenge, it is not obvious that a complete catalog and partial analysis of all proteins in a few target genomes would be a major advance toward understanding and predicting the function of complex microbial systems.

In going forward, some questions need to be considered:

  • Do we need a complete catalog of all parts, or do we want only to describe some parts?

  • If we want to focus only on some parts, what are they, and how do we identify them?

  • Given a complete catalog of parts, do we care equally about all interactions between parts?

  • Do we care equally about where every part resides, in every genotype, and under every condition, or do we care more about some parts under specific conditions?

It stands to reason that for any given situation only a small portion of the “parts” need to be understood in great detail to model system function. Such control points might be genes, alleles, proteins, metabolites, genotypes, or even taxa and their relative spatial distribution. Moreover, the specific control points may vary between different systems and situations. Developing methods of identifying such control points would be a major step toward predicting system function. Moreover, it would allow research to focus on relevant aspects of systems rather than all aspects irrespective of their relative importance.

It is not clear that describing the protein components of individual cells or multiorganism consortia is a necessary first step toward systems biology. Forefront science requires taking a step beyond that, into a detailed characterization of target systems by highly interdisciplinary teams of scientists. In the course of such an endeavor, enumeration of individual components and their interrelationships emerges naturally because it is driven by the complexity of the specific systems under study, as revealed by an integrated approach to their analysis. The technologies (both new and existing) are more effectively limited to those which are appropriate, and this is both time-efficient and cost-effective.

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