ABSTRACT

High-throughput sequencing and computerized genome annotation combined with proteomics approaches have contributed to the identifi cation of most of the basic components of the eukaryotic cell. However, despite this, we are still far from understanding how a cell functions. To reach this goal, we need to understand how cellular processes are generated from interactions between the cell’s components. To cell biologists, phenotypes are thus of more interest than genomes because they are the observations that need explaining. Characterization of cellular phenotypes in gene perturbation experiments is the standard way of establishing causal relationships between genes and phenotypes and provides the most reliable way of assigning functions to genes. Phenotyping cells has thus long provided insights into cellular functions. However, the cost of phenotyping being higher than that of genotyping, gene identifi cation has largely outpaced gene function characterization. As a result, 13 years after the completion of the human genome project, less than a third of the human protein-coding genes have been experimentally assigned a function. This points to phenotyping becoming the bottleneck in the

Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.