| Like other life sciences, nutrition science can benefit enormously from the techniques of bioinformatics. Here, the steps necessary to enable bioinformatic approaches in nutrition research are outlined, from the short-range goal of data availability in author-defined formats to the longer range goals of nutrition experiment standardization and migration of all experimental data into databases. Several examples of what will be possible for nutrition researchers in this new paradigm are described.;One aspect of food that has not been interrogated for its nutritional value is its structure. Mammalian milk provides examples of food structures ingeniously designed for nutritional advantages, such as delaying the rate of macronutrient absorption. Technologies that may be leveraged to investigate physiological responses to foods are proposed.;Bringing theory to practice, bioinformatics techniques are applied to understand the molecular biology of milk production. Mammary gland microarray data, cellular localization data, protein-protein interactions, and literature-mined genes were integrated and analyzed using statistics, principal component analysis, gene ontology analysis, pathway analysis, and network analysis to identify global biological principles that govern molecular events during pregnancy, lactation, and involution. Several key principles were derived: (1) nearly a third of the transcriptome fluctuates to build, run, and disassemble the lactation apparatus; (2) genes encoding the secretory machinery are transcribed prior to lactation; (3) the diversity of the endogenous portion of the milk proteome is derived from fewer than 100 transcripts; (4) the lactation switch is primarily post-transcriptionally mediated; (5) the secretion of materials during lactation occurs not by up-regulation of novel genomic functions, but by widespread transcriptional suppression of functions such as protein degredation and cell-environment communication; (6) the involution switch is primarily transcriptionally mediated; and (7) during early involution, the transcriptional state is partially reverted to the pre-lactation state. A new hypothesis for secretory dimunition is suggested---milk production gradually declines because the secretory machinery is not transcriptionally replenished. A comprehensive network of protein interactions during lactation is assembled and new regulatory gene targets are identified. Less than one fifth of the transcriptionally regulated nodes in this lactation network have been previously explored in the context of lactation. |
