phenotype. Rosetta stone approach The Rosetta stone approach is a computational method for de-novo protein function prediction. It is based on the hypothesis that some proteins involved in a given physiological process may exist as two separate genes in one organism and as a single gene in another. Genomes are scanned for sequences that are independent in one organism and in a single open reading frame in another. If two genes have fused, it is predicted that they have similar biological functions that make such co-regulation advantageous. Bioinformatics methods for Functional genomics Because of the large quantity of data produced by these techniques and the desire to find biologically meaningful patterns, bioinformatics is crucial to analysis of functional genomics data. Examples of techniques in this class are data clustering or principal component analysis for unsupervised machine learning (class detection) as well as artificial neural networks or support vector machines for supervised machine learning (class prediction, classification). Functional enrichment analysis is used to determine the extent of over- or under-expression (positive- or negative- regulators in case of RNAi screens) of functional categories relative to a background sets. Gene ontology based enrichment analysis are provided by DAVID and gene set enrichment analysis (GSEA), pathway based analysis by Ingenuity and Pathway studio and protein complex based analysis by COMPLEAT. New computational methods have been developed for understanding the results of a deep mutational scanning experiment. 'phydms' compares the result of a deep mutational scanning experiment to a phylogenetic tree. This allows the user to infer if the selection process in nature applies similar constraints on a protein as the results of the deep mutational scan indicate. This may allow an experimenter to choose between different experimental conditions based on how well they reflect nature. Deep mutational scanning has also been used to infer protein-protein interactions. The authors used a thermodynamic model to predict the effects of mutations in different parts of a dimer. Deep mutational structure can also be used to infer protein structure. Strong positive epistasis between two mutations in a deep mutational scan can be indicative of two parts of the protein that are close to each other in 3-D space. This information can then be used to infer protein structure. A proof of principle of this approach was shown by two groups using the protein GB1. Results from MPRA experiments have required machine learning approaches to interpret the data. A