Meta-prediction of protein subcellular localization with reduced voting

Meta-prediction seeks to harness the combined strengths of multiple predicting programs with the hope of achieving predicting performance surpassing that of all existing predictors in a defined problem domain. We investigated meta-prediction for the four-compartment eukaryotic subcellular localization problem. We compiled an unbiased subcellular localization dataset of 1693 nuclear, cytoplasmic, mitochondrial and extracellular animal proteins from Swiss-Prot 50.2. Using this dataset, we assessed the predicting performance of 12 predictors from eight independent subcellular localization predicting programs: ELSPred, LOCtree, PLOC, Proteome Analyst, PSORT, PSORT II, SubLoc and WoLF PSORT. Gorodkin correlation coefficient (GCC) was one of the performance measures. Proteome Analyst is the best individual subcellular localization predictor tested in this four-compartment prediction problem, with GCC = 0.811. A reduced voting strategy eliminating six of the 12 predictors yields a meta-predictor (RAW-RAG-6) with GCC = 0.856, substantially better than all tested individual subcellular localization predictors (P = 8.2 × 10−6, Fisher's Z-transformation test). The improvement in performance persists when the meta-predictor is tested with data not used in its development. This and similar voting strategies, when properly applied, are expected to produce meta-predictors with outstanding performance in other life sciences problem domains

A compendium of genetic regulatory effects across pig tissues

The Farm Animal Genotype-Tissue Expression (FarmGTEx) project has been established to develop a public resource of genetic regulatory variants in livestock, which is essential for linking genetic polymorphisms to variation in phenotypes, helping fundamental biological discovery and exploitation in animal breeding and human biomedicine. Here we show results from the pilot phase of PigGTEx by processing 5,457 RNA-sequencing and 1,602 whole-genome sequencing samples passing quality control from pigs. We build a pig genotype imputation panel and associate millions of genetic variants with five types of transcriptomic phenotypes in 34 tissues. We evaluate tissue specificity of regulatory effects and elucidate molecular mechanisms of their action using multi-omics data. Leveraging this resource, we decipher regulatory mechanisms underlying 207 pig complex phenotypes and demonstrate the similarity of pigs to humans in gene expression and the genetic regulation behind complex phenotypes, supporting the importance of pigs as a human biomedical model.</p

Simultaneous Characterization of Lipid sn-Positional and Double-Bond Positional Isomers using On-Demand Electrochemical Mass Spectrometry

We present an on-demand electrochemical mass spectrometry workflow for lipid structural characterization with the capability of identifying double-bond and sn-positional isomers. Two voltage-controlled electrochemical reactions, interfacial electro-epoxidation and anodic corrosion of a cobalt electrode, are cascaded in this strategy. The epoxidized products and Co-adducted ions of lipids are fragmented in tandem MS to generate structure characteristic fragments that indicate double-bond and sn-positions. The unique feature of this workflow lies in the sequential localization of double bonds, elucidation of sn-positions, and collection of native lipid information in a single system and simply by tuning ESI voltages. This feature, as well as low sample consumption, no need for extra apparatus, and quantitative analysis, should allow wide applications in the lipidomic field

Effect of Titanium Modification on Microstructure and Impact Toughness of High-Boron Multi-Component Alloy

This work investigated the microstructure and mechanical property of high-boron multi-component alloy with Fe, B, C, Cr, Mo, Al, Si, V, Mn and different contents of Ti. The results indicate that the as-cast metallurgical microstructure of high-boron multi-component alloys consist of ferrite, pearlite and borocarbide. In an un-modified alloy, continuous reticular structure of borocarbide is observed. After titanium addition, the structure of borocarbide changes into a fine and isolated morphology. TiC is the existence form of titanium in the alloy, which acts as the heterogeneous nuclei for eutectic borocarbide. Moreover, impact toughness of the alloy is remarkably improved by titanium modification

Interfacial Electro-Epoxidation in Electrospray Ionization Mass Spectrometry for Simultaneous Analysis of Negatively and Positively Charged Unsaturated Glycerophospholipids

In this study, we developed an AC-induced interfacial electro-epoxidation reaction for localization of double-bonds in nega-tively and positively charged forms of lipids simultaneously. An AC voltage plays multiple roles in this method, including initiation of the electrochemical epoxidation of double-bonds in both charge states of lipids, and protonation and deprotona-tion of lipid for detection in both ion modes. The advantages of simultaneous detection of negatively changed and positively charged unsaturated lipids, voltage-controlled electrochemical derivatization, and the low sample consumption allow its wide applications in a broad range of lipid-related research

A Cost Modeling Method Based on AADL2

The Architecture Analysis and Design Language (AADL) is widely used in the modeling, analysis and verification of the dependability-critical system. Previously, we have implemented the multi-objective (based on dependability and cost) architecture optimization analysis of the AADL model. The cost attribute modeling, however, was only assumed to be a simple numerical value. It cannot accurately reflect the actual cost model. In addition, there is still a lack of mature cost modeling methods for AADL. In this paper, we develop a cost modeling method for the latest AADL2. The factors that affect the cost of components and systems are firstly summarized and concluded. Based on those summarized factors, a cost meta-model is secondly abstracted and developed. The cost meta-model is finally defined as a property set in the AADL model. With this cost property set, users can not only use the developed life cycle cost properties directly, but also can define individualized cost properties to meet specific cost requirements. The proposed method has greatly extended the cost modeling capabilities for the AADL

First-Principles Investigations of the Structural, Anisotropic Mechanical, Thermodynamic and Electronic Properties of the AlNi2Ti Compound

In this paper, the electronic, mechanical and thermodynamic properties of AlNi2Ti are studied by first-principles calculations in order to reveal the influence of AlNi2Ti as an interfacial phase on ZTA (zirconia toughened alumina)/Fe. The results show that AlNi2Ti has relatively high mechanical properties, which will benefit the impact or wear resistance of the ZTA/Fe composite. The values of bulk, shear and Young’s modulus are 164.2, 63.2 and 168.1 GPa respectively, and the hardness of AlNi2Ti (4.4 GPa) is comparable to common ferrous materials. The intrinsic ductile nature and strong metallic bonding character of AlNi2Ti are confirmed by B/G and Poisson’s ratio. AlNi2Ti shows isotropy bulk modulus and anisotropic elasticity in different crystallographic directions. At room temperature, the linear thermal expansion coefficient (LTEC) of AlNi2Ti estimated by quasi-harmonic approximation (QHA) based on Debye model is 10.6 × 10−6 K−1, close to LTECs of zirconia toughened alumina and iron. Therefore, the thermal matching of ZTA/Fe composite with AlNi2Ti interfacial phase can be improved. Other thermodynamic properties including Debye temperature, sound velocity, thermal conductivity and heat capacity, as well as electronic properties, are also calculated

Lipid Isobaric Mass Tagging for Enhanced Relative Quantification of Unsaturated <i>sn</i>-Positional Isomers

Changes in the levels of lipid sn-positional isomers are associated with perturbation of the physiological environment within the biological system. Consequently, knowing the concentrations of these lipids holds significant importance for unraveling their involvement in disease diagnosis and pathological mechanisms. However, existing methods for lipid quantification often fall short in accuracy due to the structural diversity and isomeric forms of lipids. To address this challenge, we have developed an aziridine-based isobaric tag labeling strategy that allows (i) differentiation and (ii) enhanced relative quantification of lipid sn-positional isomers from distinct samples in a single run. The methodology enabled by aziridination, isobaric tag labeling, and lithiation has been applied to various phospholipids, enabling the determination of the sn-positions of fatty acyl chains and enhanced relative quantification. The analysis of Escherichia coli lipid extracts demonstrated the enhanced determination of the concentration ratios of lipid isomers by measuring the intensity ratios of mass reporters released from sn-positional diagnostic ions. Moreover, we applied the method to the analysis of human colon cancer plasma. Intriguingly, 17 PC lipid sn-positional isomers were identified and quantified simultaneously, and among them, 7 showed significant abundance changes in the colon cancer plasma, which can be used as potential plasma markers for diagnosis of human colon cancer