Systems biology efforts are increasingly adopting quantitative, mechanistic modeling to study cellular signal transduction pathways and other networks. However, it is uncertain whether the particular set of kinetic parameter values of the model closely approximates the corresponding biological system. We propose that the parameters be assigned statistical distributions that reflect the degree of uncertainty for a comprehensive simulation analysis. From this analysis, we globally identify the key components and steps in signal transduction networks at a systems level. We investigated a recent mathematical model of interferon gamma induced Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway by applying multi-parametric sensitivity analysis that is based on simultaneous variation of the parameter values. We find that suppressor of cytokine signaling-1, nuclear phosphatases, cytoplasmic STAT1, and the corresponding reaction steps are sensitive perturbation points of this pathway.
A high-performance method was developed for protein secondary structure prediction based on the dual-layer support vector machine (SVM) and position-specific scoring matrices (PSSMs). SVM is a new machine learning technology that has been successfully applied in solving problems in the field of bioinformatics. The SVM's performance is usually better than that of traditional machine learning approaches. The performance was further improved by combining PSSM profiles with the SVM analysis. The PSSMs were generated from PSI-BLAST profiles, which contain important evolution information. The final prediction results were generated from the second SVM layer output. On the CB513 data set, the three-state overall per-residue accuracy, Q3, reached 75.2%, while segment overlap (SOV) accuracy increased to 80.0%. On the CB396 data set, the Q3 of our method reached 74.0% and the SOV reached 78.1%. A web server utilizing the method has been constructed and is available at http://www.bioinfo.tsinghua.edu.cn/pmsvm.
BackgroundSubcellular localization information is one of the key features to protein function research. Locating to a specific subcellular compartment is essential for a protein to function efficiently. Proteins which have multiple localizations will provide more clues. This kind of proteins may take a high proportion, even more than 35%.DescriptionWe have developed a database of proteins with multiple subcellular localizations, designated DBMLoc. The initial release contains 10470 multiple subcellular localization-annotated entries. Annotations are collected from primary protein databases, specific subcellular localization databases and literature texts. All the protein entries are cross-referenced to GO annotations and SwissProt. Protein-protein interactions are also annotated. They are classified into 12 large subcellular localization categories based on GO hierarchical architecture and original annotations. Download, search and sequence BLAST tools are also available on the website.ConclusionDBMLoc is a protein database which collects proteins with more than one subcellular localization annotation. It is freely accessed at .
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