ExonImpact: prioritizing pathogenic alternative splicing events

Alternative splicing (AS) is a closely regulated process that allows a single gene to encode multiple protein isoforms, thereby contributing to the diversity of the proteome. Dysregulation of the splicing process has been found to be associated with many inherited diseases. However, among the pathogenic AS events, there are numerous “passenger” events whose inclusion or exclusion does not lead to significant changes with respect to protein function. In this study, we evaluate the secondary and tertiary structural features of proteins associated with disease-causing and neutral AS events, and show that several structural features are strongly associated with the pathological impact of exon inclusion. We further develop a machine-learning-based computational model, ExonImpact, for prioritizing and evaluating the functional consequences of hitherto uncharacterized AS events. We evaluated our model using several strategies including cross-validation, and data from the Gene-Tissue Expression (GTEx) and ClinVar databases. ExonImpact is freely available at http://watson.compbio.iupui.edu/ExonImpact

regSNPs-splicing: a tool for prioritizing synonymous single-nucleotide substitution

While synonymous single-nucleotide variants (sSNVs) have largely been unstudied, since they do not alter protein sequence, mounting evidence suggests that they may affect RNA conformation, splicing, and the stability of nascent-mRNAs to promote various diseases. Accurately prioritizing deleterious sSNVs from a pool of neutral ones can significantly improve our ability of selecting functional genetic variants identified from various genome-sequencing projects, and, therefore, advance our understanding of disease etiology. In this study, we develop a computational algorithm to prioritize sSNVs based on their impact on mRNA splicing and protein function. In addition to genomic features that potentially affect splicing regulation, our proposed algorithm also includes dozens structural features that characterize the functions of alternatively spliced exons on protein function. Our systematical evaluation on thousands of sSNVs suggests that several structural features, including intrinsic disorder protein scores, solvent accessible surface areas, protein secondary structures, and known and predicted protein family domains, show significant differences between disease-causing and neutral sSNVs. Our result suggests that the protein structure features offer an added dimension of information while distinguishing disease-causing and neutral synonymous variants. The inclusion of structural features increases the predictive accuracy for functional sSNV prioritization

Multi-modes control method for spacecraft formation establishment and reconfiguration near the libration points

AbstractThis paper studies Multi-modes control method for libration points formation establishment and reconfiguration. Firstly, relations between optimal impulse control and Floquet modes are investigated. Method of generating modes is proposed. Characteristics of the mode coefficients stimulated at different time are also given. Studies show that coefficients of controlled modes can be classified into four types, and formation establishment and reconfiguration can be achieved by multi-impulse control with the presented method of generating modes. Then, since libration points formation is generally unstable, mutli-modes keeping control method which can stabilize five Floquet modes simultaneously is proposed. Finally, simulation on formation establishment and reconfiguration are carried out by using method of generating modes and mutli-modes keeping control method. Results show that the proposed control method is effective and practical

PREPARATION OF ULTRA-THIN CATION EXCHANGE COMPOSITE MEMBRANES BY A NOVEL PLASMA POLYMERIZATION TECHNIQUE

An after-glow capacitively coupled discharge technique has been used to fabricate ultra-thin proton exchange composite membranes in a plasma polymerization reactor, where styrene and acrylic acid are used as starting materials. By this technique, a good preservation of monomer structure can be achieved. The structure and composition of the plasma polymerized membranes were characterized by X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FT-IR). The morphology information and thickness of the membranes were provided by Scanning electron micrographs (SEM). The synthesized membranes are dense with uniform structure and rich with carboxyl acid groups. This novel plasma polymerization technique is expected to be used for the preparation of alternative membranes to preserve their monomer structure to a maximum extent.Plasma polymerization, Fourier transform infrared spectroscopy, acrylic acid, plasma composite membranes

PREPARATION OF HIGHLY SULFONATED ULTRA-THIN PROTON-EXCHANGE POLYMER MEMBRANES FOR PROTON EXCHANGE MEMBRANE FUEL CELLS

Sulfonated ultra-thin proton-exchange polymer membrane carrying pyridine groups was made from a plasma polymerization of styrene, 2-vinylpyridine, and trifluoromethanesulfonic acid by after-glow capacitively coupled discharge technique. Pyridine groups tethered to the polymer backbone acts as a medium through the basic nitrogen for transfer of protons between the sulfonic acid groups of proton exchange membrane. It shows that the method using present technology could effectively depress the degradation of monomers during the plasma polymerization. Spectroscopic analyses reveal that the obtained membranes are highly functionalized with proton exchange groups and have higher proton conductivity. Thus, the membranes are expected to be used in direct methanol fuel cells.Plasma polymerization, proton-exchange polymer membranes, composite materials, electron microscopy, chemical vapor deposition