From proteomics to systems biology of bacterial pathogens: approaches, tools, and applications.

The hallmark of a systems biology approach is the integration of computational tools with experimental data encompassing multiple classes of biomolecules across different functional levels. Equally important as the availability of reasonably comprehensive information at the gene, protein, and metabolite levels is the development of adequate analysis and visualization tools to reduce the inherent complexity to interpretable dimensions. In this paper, we describe the integration of a 2-D gel-based proteome map of Staphylococcus aureus Mu50 with genomic and transcriptomic information through a customized data integration and user interface built on the Ensembl genome browser. We illustrate its application and potential through the analysis of a defined system perturbation caused by a mutation in the formyltransferase gene. We envision that this software package, which we called Insieme, can support the development of novel antibiotics by allowing a systems-based view of the bacterial response pathways.

Evaluation of biomarker discovery approaches to detect protein biomarkers of acute renal allograft rejection.

Management of host responses to allografts by immunosuppressive therapy is the cornerstone of transplantation medicine, but it is still deficient in one important element: biomarkers that are readily accessible and predict the fate of the transplant early, specifically, and reliably. Using a Brown Norway (BN)-to-Lewis rat renal allograft model of kidney transplantation, this study aims at evaluating two proteomic approaches to discover biomarkers for acute rejection: SELDI-MS technology and 2D gel electrophoresis combined with mass spectrometry. Several novel potential serum biomarkers have been identified for follow up. Overall, the conclusion is that apparently at the serum protein level, dramatic changes only occur at a stage where kidney function is already severely affected. Multivariate analysis of serum profiles suggests that there is an ensemble of subtle changes, comprising a proteomic signature of acute rejection at an early stage, a more detailed evaluation of which might provide novel opportunities for the diagnosis of acute rejection. Profiling of the excreted proteins indicates that urine might even present the earliest signs of the rejection process.