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Pig in spacePigSpace: An Interactive Environment for
Analyzing Genes and Environment in Heart Disease

The promise of personalized medicine is a revolution in treating individuals rather than groups. Personalized medicine is patient-centered, treating each person according to a custom situation rather than physician-centered, treating each disease according to its standard progression. Personal Health is a combination of many factors, each with individual variation. Some factors are in the genes, resulting in a particular bodytype with particular susceptibility to stimuli. Some factors are in the environment, resulting in a particular lifestyle that provides stimuli. The combination of genes and environment produce a custom situation that yields a health status.

The promise of genomic biology is that personalized medicine can be achieved via using functional analysis of animal genomes. Although there are some diseases where genes are the primary causation, the diseases that adversely affect the health of most people are complicated combinations. For example, certain body types are more susceptible to heart disease no matter what the lifestyle (obesity genes). Conversely, certain lifestyles are more susceptible to heart disease no matter what the bodytype (environment stress). Measuring personal health requires analyzing the physiology of bodytype and the psychology of lifestyle. Improving personal health requires individualized medicine (targeted drugs) and lifestyle modification (diet and exercise).

We propose a grand project in personalized medicine, to develop health predictors for heart diseases. We will use the analytic technologies of genomic biology, with the pig as the animal model for human health. The pig has been the classic model for studying heart diseases, due to its close physical and functional analogues to the human. Pigs can now be cloned, so that controlled experiments are possible to relate genotype to phenotype. For example, different animals with identical genetics can have modified lifestyles with different diet and exercise regimes, then the effects on heart condition precisely measured.

The biology part of the PigSpace project will be led by Larry Schook, who is the Principal Investigator of the pig genome project being funded by USDA. The sequencing is underway at the Sanger Center and will form the underlying basis for the genome analysis of heart regions. His personal laboratory is pioneering phenotype mapping for cloned pigs. The informatics part of the PigSpace project will be led by Bruce Schatz, who is the Principal Investigator of the BeeSpace project being funded by NSF. The software development is underway at the Institute for Genomic Biology and will form the underlying basis for the functional analysis for heart health. His personal laboratory is pioneering phenotype clustering for human populations.

BeeSpace is developing an interactive environment for functional analysis of genes and environment in social behavior. Wet lab analysis of microarray expressions in honey bees is used to record gene clusters relevant to social behaviors. Dry lab analysis of biomedical literature and genome databases is used to discover functional clusters for these gene clusters. Each microarray experiment records a different combination of genes and environment, to evaluate relative contributions of nature and nurture. The BeeSpace software will be the basis of the PigSpace software, as text analysis of biomedical literature is common to bees and pigs. The genome databases for BeeSpace use the fly as model organism; those for PigSpace would use the mouse as model, or possibly the more recent rat genome database.

The project is being carried out in the Animal Bioinformatics Laboratory (B. Schatz lead) at the Institute for Genomic Biology at the University of Illinois. This Bioinformatics Laboratory is shared between the Neurobiology Genomics Theme (G. Robinson lead), where BeeSpace is being developed, and the Regenerative Biology Theme (L. Schook lead), where PigSpace is being developed. The Medical research is being carried out in association with the Carle Foundation Hospital in Urbana Illinois for the heart analysis and health analysis.

PigSpace supports conceptual navigation within an information space across all the sources: literature and genome, populations and individuals. The major steps to develop are:

(1) Genome Analysis of Heart Regions. (PigBase)

A region by region analysis of the pig sequence as to which segments of the genome control which segments of the circulatory system. Human Heart diseases are typically described by the segments of failure, such as congestive heart failure (pump failure), coronary artery (pipe blockage), atherosclerosis (wall decay), and so on. Experimentally this can be done by recording gene expressions in pigs that have each particular heart condition and using the annotation pipeline adapted from the BeeSpace environment to functionally analyze each gene cluster.

(2) Phenotype Mapping for Pig. (Heart Analysis)

An experimental investigation of the relative contributions of genes and environment on heart disease in the pig. Multiple cloned pigs are separately given different regimes of diet and exercise, then their hearts examined for plaque development and other failures. In addition to lifestyle experiments on the pig clone, genome scanning is systematically done of different breeds representing different bodytypes. This attempts to incorporate genetic (population) variation into the phenotype mapping by QTL analysis via SNP scanning across bodytypes.

(3) Phenotype Clustering for Human. (Health Analysis)

An experimental investigation of population cohorts for heart disease across health factors. Human patients are clustered into cohorts based on similar features, by asking daily questions chosen adaptively for the particular patient across the entire spectrum of health factors. Such factors include physiological measures such as pain and mobility as well as psychological measures such as stress and sociality. The health monitors are deployed via the Internet to self-administer the status questionnaires via home computers. The test population will attempt to include a range of bodytypes to incorporate environmental (individual) variation into measures.

(4) Functional Analysis of Heart Health. (PigSpace)

A bodytype by bodytype analysis of human health related to heart disease. For each bodytype, the likely outcomes of different lifestyles are given. These outcomes are inferred from (2) and (3), where (2) gives what outcome occurs with each combination of bodytype and lifestyle in pig, while (3) gives the cohort clusters for human. Bodytype and Lifestyle are approximations for routine and accurate genotypes and phenotypes. Functional analysis matches up human cohorts to pig clusters via supporting evidence. Part of the evidence is data analysis from pig individuals and human populations, while part is text analysis from biomedical literature of health status in similar cohorts.

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