Prequips--an extensible software platform for integration, visualization and analysis of LC-MS/MS proteomics data.

SUMMARY: We describe an integrative software platform, Prequips, for comparative proteomics-based systems biology analysis that: (i) integrates all information generated from mass spectrometry (MS)-based proteomics as well as from basic proteomics data analysis tools, (ii) visualizes such information for various proteomic analyses via graphical interfaces and (iii) links peptide and protein abundances to external tools often used in systems biology studies. AVAILABILITY: http://prequips.sourceforge.net

A systems approach to prion disease.

Prions cause transmissible neurodegenerative diseases and replicate by conformational conversion of normal benign forms of prion protein (PrP(C)) to disease-causing PrP(Sc) isoforms. A systems approach to disease postulates that disease arises from perturbation of biological networks in the relevant organ. We tracked global gene expression in the brains of eight distinct mouse strain-prion strain combinations throughout the progression of the disease to capture the effects of prion strain, host genetics, and PrP concentration on disease incubation time. Subtractive analyses exploiting various aspects of prion biology and infection identified a core of 333 differentially expressed genes (DEGs) that appeared central to prion disease. DEGs were mapped into functional pathways and networks reflecting defined neuropathological events and PrP(Sc) replication and accumulation, enabling the identification of novel modules and modules that may be involved in genetic effects on incubation time and in prion strain specificity. Our systems analysis provides a comprehensive basis for developing models for prion replication and disease, and suggests some possible therapeutic approaches.

MS-BID: a Java package for label-free LC-MS-based comparative proteomic analysis.

UNLABELLED: MS-BID (MS Biomarker Discovery Platform) is an integrative computational pipeline for biomarker discovery using LC-MS-based comparative proteomic analysis. This platform consists of several computational tools for: (i) detecting peptides in the collected patterns; (ii) matching detected peptides across a number of LC-MS datasets and (iii) selecting discriminatory peptides between classes of samples. AVAILABILITY: MS-BID source codes, binaries and documentations are freely available under LGPL from http://tools.proteomecenter.org/msBID.php.

The Prion Disease Database: a comprehensive transcriptome resource for systems biology research in prion diseases.

Prion diseases reflect conformational conversion of benign isoforms of prion protein (PrP(C)) to malignant PrP(Sc) isoforms. Networks perturbed by PrP(Sc) accumulation and their ties to pathological events are poorly understood. Time-course transcriptomic and phenotypic data in animal models are critical for understanding prion-perturbed networks in systems biology studies. Here, we present the Prion Disease Database (PDDB), the most comprehensive data resource on mouse prion diseases to date. The PDDB contains: (i) time-course mRNA measurements spanning the interval from prion inoculation through appearance of clinical signs in eight mouse strain-prion strain combinations and (ii) histoblots showing temporal PrP(Sc) accumulation patterns in brains from each mouse-prion combination. To facilitate prion research, the PDDB also provides a suite of analytical tools for reconstructing dynamic networks via integration of temporal mRNA and interaction data and for analyzing these networks to generate hypotheses.Database URL:http://prion.systemsbiology.net.

Genomic analysis of the olfactory receptor region of the mouse and human T-cell receptor alpha/delta loci.

We have conducted a comparative genomic analysis of several olfactory receptor (OR) genes that lie immediately 5' to the V-alpha gene segments at the mouse and human T-cell receptor (TCR) alpha/delta loci. Five OR genes are identified in the human cluster. The murine cluster has at least six OR genes; the first five are orthologous to the human genes. The sixth mouse gene has arisen since mouse-human divergence by a duplication of a approximately 10-kb block. One pair of OR paralogs found at the mouse and human loci are more similar to each other than to their corresponding orthologs. This paralogous "twinning" appears to be under selection, perhaps to increase sensitivity to particular odorants or to resolve structurally-similar odorants. The promoter regions of the mouse OR genes were identified by RACE-PCR. Orthologs share extensive 5' UTR homology, but we find no significant similarity among paralogs. These findings extend previous observations that suggest that OR genes do not share local significant regulatory homology despite having a common regulatory agenda. We also identified a diverged TCR-alpha gene segment that uses a divergent recombination signal sequence (RSS) to initiate recombination in T-cells from within the OR region. We explored the hypothesis that OR genes may use DNA recombination in expressing neurons, e.g., to recombine ORs into a transcriptionally active locus. We searched the mouse sequence for OR-flanking RSS motifs, but did not find evidence to suggest that these OR genes use TCR-like recombination target sequences.