Predicting essential proteins by integrating orthology, gene expressions, and PPI networks

<div><p>Identifying essential proteins is very important for understanding the minimal requirements of cellular life and finding human disease genes as well as potential drug targets. Experimental methods for identifying essential proteins are often costly, time-consuming, and laborious. Many computational methods for such task have been proposed based on the topological properties of protein-protein interaction networks (PINs). However, most of these methods have limited prediction accuracy due to the noisy and incomplete natures of PINs and the fact that protein essentiality may relate to multiple biological factors. In this work, we proposed a new centrality measure, OGN, by integrating orthologous information, gene expressions, and PINs together. OGN determines a protein’s essentiality by capturing its co-clustering and co-expression properties, as well as its conservation in the evolution process. The performance of OGN was tested on the species of <i>Saccharomyces cerevisiae</i>. Compared with several published centrality measures, OGN achieves higher prediction accuracy in both working alone and ensemble.</p></div

Influence of ion exchange resin on the performance of continuous electrodeionization (CEDI) treating low-level radioactive wastewater

<p>With the fast development of nuclear power, low-level radioactive wastewater (LLRW) treatment will meet more severe requirements. Continuous electrodeionization (CEDI) is a novel technology to treat LLRW with advantages of lower level effluent and smaller waste production. In this study, the influences of ion exchange resins (IERs) in the concentrate and dilute compartments on the performance of CEDI were investigated. The three stacks filled with anion exchange resins in the dilute compartments were more efficient for boron removal than metal ions, while the three stacks filled with cation exchange resins were more efficient for the removal of metal ions than boron. The stack filled with a type of mixed IERs was good at removing both metal ions and boron. The correlation analysis showed that no significant correlations were found between ion exchange capacities or ion exchange kinetics with the decontamination factors of metal ions. The removal ratios of boron were positively correlated with the ion exchange capacities, but were not correlated with the ion exchange kinetics. The results can guide the CEDI stack design by filling different IERs for different purposes.</p

Dissecting the Effect of Temperature on Hyperthermophilic Pf2001 Esterase Dimerization by Molecular Dynamics

Pf2001 esterase (Pf2001) from Pyrococcus furiosus has hyperthermophilic properties and exerts a biocatalytic function in a dimeric state. Crystal structures revealed that the structural rearrangement of the cap domain is responsible for the Pf2001 dimer formation. However, the details of the cap domain remodeling and the effects of temperature on the dimerization process remain elusive at the molecular level, taking into account that experimental methods are difficult to capture the dynamic process of dimerization to some extent. Herein, four dimer models based on the monomeric crystal structure (PDB ID: 5G59) were constructed to investigate the conformational transition details and temperature effects in the dimerization by conventional molecular dynamics and accelerated molecular dynamics simulations. Our simulation results indicate that the monomer undergoes a conformational change into a “preparatory state” at high temperatures, which is more favorable for its transformation into a stable dimer. The subsequent free energy landscape analysis further identifies four intermediate states (from separated state to dimeric state) and discloses that a more accessible α-helix driven by stronger hydrophobic interactions induces a rearrangement of the cap domain, displaying a “tic-tac-toe” activation feature that is important for stabilizing the dimer interface and facilitating the formation of hydrophobic pockets. In addition, the electrostatic potential surface analysis illustrates that the weaker electrostatic repulsion (Lys and Arg) in the dimer interface at high temperatures is also a key factor for dimer stabilization. Altogether, our results can provide molecular-level insight into the dimer formation process of hyperthermophilic esterase and would be useful to understand the enzymatic specificity of α/β-hydrolase

The protein interaction network for the top 100 selected proteins by OGN (alpha = 0.3).

<p>The protein interaction network for the top 100 selected proteins by OGN (alpha = 0.3).</p

Dissecting the Effect of Temperature on Hyperthermophilic Pf2001 Esterase Dimerization by Molecular Dynamics

Pf2001 esterase (Pf2001) from Pyrococcus furiosus has hyperthermophilic properties and exerts a biocatalytic function in a dimeric state. Crystal structures revealed that the structural rearrangement of the cap domain is responsible for the Pf2001 dimer formation. However, the details of the cap domain remodeling and the effects of temperature on the dimerization process remain elusive at the molecular level, taking into account that experimental methods are difficult to capture the dynamic process of dimerization to some extent. Herein, four dimer models based on the monomeric crystal structure (PDB ID: 5G59) were constructed to investigate the conformational transition details and temperature effects in the dimerization by conventional molecular dynamics and accelerated molecular dynamics simulations. Our simulation results indicate that the monomer undergoes a conformational change into a “preparatory state” at high temperatures, which is more favorable for its transformation into a stable dimer. The subsequent free energy landscape analysis further identifies four intermediate states (from separated state to dimeric state) and discloses that a more accessible α-helix driven by stronger hydrophobic interactions induces a rearrangement of the cap domain, displaying a “tic-tac-toe” activation feature that is important for stabilizing the dimer interface and facilitating the formation of hydrophobic pockets. In addition, the electrostatic potential surface analysis illustrates that the weaker electrostatic repulsion (Lys and Arg) in the dimer interface at high temperatures is also a key factor for dimer stabilization. Altogether, our results can provide molecular-level insight into the dimer formation process of hyperthermophilic esterase and would be useful to understand the enzymatic specificity of α/β-hydrolase

Performance of ensemble method with different top <i>n</i> and threshold <i>T</i>.

<p>Performance of ensemble method with different top <i>n</i> and threshold <i>T</i>.</p

Comparison of OGN, CoEWC, SON, LBCC, and five common used centrality measures (BC, CC, DC, EC, and SC) using Jackknife method.

<p>Comparison of OGN, CoEWC, SON, LBCC, and five common used centrality measures (BC, CC, DC, EC, and SC) using Jackknife method.</p

Online_Supplement – Supplemental material for Assessing Item-Level Fit for Higher Order Item Response Theory Models

<p>Supplemental material, Online_Supplement for Assessing Item-Level Fit for Higher Order Item Response Theory Models by Xue Zhang, Chun Wang and Jian Tao in Applied Psychological Measurement</p

Precision-recall curves of OGN with different α.

<p>Precision-recall curves of OGN with different α.</p

The number of true essential proteins identified by OGN with different α.

<p>The number of true essential proteins identified by OGN with different α.</p