Integrating physical and genetic maps: from genomes to interaction networks

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Abstract
The integration of genetic and physical maps was a defining feature of the Human Genome Project. Mapping of the cell's regulatory and signalling networks is now proceeding along highly analogous lines. A first step in sequencing the human genome was to assign quality scores to each sequenced nucleotide. In the case of physical and genetic interactions, the method of choice for improving quality is integration of data across a wide variety of measurement types. Genome assembly was the process of putting sequence reads together to form contigs. In the context of molecular interactions, assembly refers to the integration of individual interactions into larger network structures that represent pathways, protein complexes and other components of cellular machinery. Network assembly is aided by a classification system for molecular interactions. Towards this goal, recent studies have begun to place interactions into various categories beyond the initial division into genetic and physical. Categories of interactions include ordered versus unordered, transient versus stable, between- versus within-pathway, alleviating versus aggravating, and interactions of the first versus second degree. These types are being combined with one another in various combinations to assemble integrated network models. Examples include integration of protein–protein interactions with aggravating, alleviating or ordered genetic interactions, as well as integration of eQTLs with protein–DNA transcriptional interactions. A final step is network annotation: inference of additional details such as interaction dynamics, strengths and condition-specificity onto the static network. Integration of genetic and physical interaction mapping data will be particularly important to the current wave of genome-wide association studies, in which many genetic interactions are apparent with little physical or mechanistic explanation.