Building an application framework for integrative genomics.

The accelerated pace of biological research and the current availability of whole-genome data sets provides significant new sources of functional insight. We designed an architecture and framework for software to query and explore such data in an orderly and iterative fashion. The architecture is intended to provide an extensible platform for developing web based bioinformatics applications and to offer a flexible and end-user-extensible software environment to explore and integrate disparate biological data sources. This will enable the user to explore existing relationships and discover new functional relationships among these data.

Providing context-sensitive decision-support based on WHO guidelines.

A decision support system was developed implementing the WHO guideline for diarrhea management. The decision-support system is integrated into a medical records application on a handheld computer. The system will be used by primary health care workers in rural India. The guideline was encoded as a set of chained rules in CLIPS format. To enhance adherence to guidelines, we use a model based on a context-adapted guideline to provide decision support at the point of care in a particular setting. The purpose of the system is to tailor the recommendations based on the patient's condition and the local factors such as resource availability in order to create feasible uniformity in a practice across different providers of care.

Integrated analysis of protein composition, tissue diversity, and gene regulation in mouse mitochondria.

Mitochondria are tailored to meet the metabolic and signaling needs of each cell. To explore its molecular composition, we performed a proteomic survey of mitochondria from mouse brain, heart, kidney, and liver and combined the results with existing gene annotations to produce a list of 591 mitochondrial proteins, including 163 proteins not previously associated with this organelle. The protein expression data were largely concordant with large-scale surveys of RNA abundance and both measures indicate tissue-specific differences in organelle composition. RNA expression profiles across tissues revealed networks of mitochondrial genes that share functional and regulatory mechanisms. We also determined a larger "neighborhood" of genes whose expression is closely correlated to the mitochondrial genes. The combined analysis identifies specific genes of biological interest, such as candidates for mtDNA repair enzymes, offers new insights into the biogenesis and ancestry of mammalian mitochondria, and provides a framework for understanding the organelle's contribution to human disease.