HOW MANY MEMBRANE-PROTEINS ARE THERE

One of the basic issues that arises in functional genomics is the abil ity to predict the subcellular location of proteins that are deduced f rom gene and genome sequencing. In particular, one would like to be ab le to readily specify those proteins that are soluble and those that a re inserted in a membrane. Traditional methods of distinguishing betwe en these two locations have relied on extensive, time-consuming bioche mical studies. The alternative approach has been to make inferences ba sed on a visual search of the amino acid sequences of presumed gene pr oducts for stretches of hydrophobic amino acids. This numerical, seque nce-based approach is usually seen as a first approximation pending mo re reliable biochemical data. The recent availability of large and com plete sequence data sets for several organisms allows us to determine just how accurate such a numerical approach could be, and to attempt t o minimize and quantify the error involved. We have optimized a statis tical approach to protein location determination. Using our approach, we have determined that surprisingly few proteins are misallocated usi ng the numerical method. We also examine the biological implications o f the success of this technique.