Proteomics: Praise, Promises and Problems

Kelvin H. Lee
Cornell University Chemical Engineering
khlee@cheme.cornell.edu
www.leelab.org

The drive to better understand the relationship between genome sequenceinformation, gene regulation and expression and biological phenomenasimultaneously challenges several disciplines and creates many newopportunities. As high-throughput DNA sequencing technology is applied toan ever increasing number of organisms, ones attention turns to a moredetailed understanding of gene regulation and expression. Indeed, the pastseveral years have seen an unprecedented amount of effort and interestdevoted to new technologies for quantitative and semi-quantitative mRNAanalysis such as serial analysis of gene expression and microarrays. At thesame time, there has been relatively little development of new technologiesfor "high-throughput" simultaneous protein expression particularly intechnologies which are discovery-based. This area is clearly an importantone and it poses many challenges. Unlike nucleic acids which vary largelyin length and in relatively few other characteristics (sequence, secondarystructures and other features are certainly important), proteins, and theamino acids which result in protein sequences, are relatively diverse.Indeed, no current technology can reliably resolve all of the proteins ofvarious hydrophobicities that are expressed in a particular cell ororganism. In as much as the Human Genome Initiative has truly benefitedfrom an initial effort to define and to develop improved technologies forgenerating DNA sequence information before a concerted effort to sequencethe Genome was mounted, we should take time to both develop newtechnologies for assessing the state of the proteome which includes ananalysis of protein expression, post-translational modifications andfunction while also applying these tools to systems which lend themselveswell to the development of predictive mathematical models. We will considergenerally accessible state-of-the art methods for proteome measurements andconsider their strengths and limitations.