scholarly journals Graph contextualized attention network for predicting synthetic lethality in human cancers

2021 ◽  
Author(s):  
Yahui Long ◽  
Min Wu ◽  
Yong Liu ◽  
Jie Zheng ◽  
Chee Keong Kwoh ◽  
...  
Keyword(s):  
Synthetic Lethality ◽  
Critical Role ◽  
Design Feature ◽  
Cost Effective ◽  
Attention Network ◽  
New Genes ◽  
Lab Experiments ◽  
Proposed Model ◽  
Multiple Feature ◽  
Wet Lab

Abstract Motivation Synthetic Lethality (SL) plays an increasingly critical role in the targeted anticancer therapeutics. In addition, identifying SL interactions can create opportunities to selectively kill cancer cells without harming normal cells. Given the high cost of wet-lab experiments, in silico prediction of SL interactions as an alternative can be a rapid and cost-effective way to guide the experimental screening of candidate SL pairs. Several matrix factorization-based methods have recently been proposed for human SL prediction. However, they are limited in capturing the dependencies of neighbors. In addition, it is also highly challenging to make accurate predictions for new genes without any known SL partners. Results In this work, we propose a novel graph contextualized attention network named GCATSL to learn gene representations for SL prediction. First, we leverage different data sources to construct multiple feature graphs for genes, which serve as the feature inputs for our GCATSL method. Second, for each feature graph, we design node-level attention mechanism to effectively capture the importance of local and global neighbors and learn local and global representations for the nodes, respectively. We further exploit multi-layer perceptron (MLP) to aggregate the original features with the local and global representations and then derive the feature-specific representations. Third, to derive the final representations, we design feature-level attention to integrate feature-specific representations by taking the importance of different feature graphs into account. Extensive experimental results on three datasets under different settings demonstrated that our GCATSL model outperforms 14 state-of-the-art methods consistently. In addition, case studies further validated the effectiveness of our proposed model in identifying novel SL pairs. Availability Python codes and dataset are freely available on GitHub (https://github.com/longyahui/GCATSL) and Zenodo (https://zenodo.org/record/4522679) under the MIT license.

scholarly journals Graph Contextualized Attention Network for Predicting Synthetic Lethality in Human Cancers

2021 ◽  
Author(s):  
Yahui Long ◽  
Min Wu ◽  
Yong Liu ◽  
Jie Zheng ◽  
Chee Keong Kwoh ◽  
...  
Keyword(s):  
Synthetic Lethality ◽  
Critical Role ◽  
Design Feature ◽  
Cost Effective ◽  
Attention Network ◽  
New Genes ◽  
Lab Experiments ◽  
Proposed Model ◽  
Multiple Feature ◽  
Wet Lab

AbstractMotivationSynthetic Lethality (SL) plays an increasingly critical role in the targeted anticancer therapeutics. In addition, identifying SL interactions can create opportunities to selectively kill cancer cells without harming normal cells. Given the high cost of wet-lab experiments, in silico prediction of SL interactions as an alternative can be a rapid and cost-effective way to guide the experimental screening of candidate SL pairs. Several matrix factorization-based methods have recently been proposed for human SL prediction. However, they are limited in capturing the dependencies of neighbors. In addition, it is also highly challenging to make accurate predictions for new genes without any known SL partners.ResultsIn this work, we propose a novel graph contextualized attention network named GCATSL to learn gene representations for SL prediction. First, we leverage different data sources to construct multiple feature graphs for genes, which serve as the feature inputs for our GCATSL method. Second, for each feature graph, we design node-level attention mechanism to effectively capture the importance of local and global neighbors and learn local and global representations for the nodes, respectively. We further exploit multi-layer perceptron (MLP) to aggregate the original features with the local and global representations and then derive the feature-specific representations. Third, to derive the final representations, we design feature-level attention to integrate feature-specific representations by taking the importance of different feature graphs into account. Extensive experimental results on three datasets under different settings demonstrate that our GCATSL model outperforms 14 state-of-the-art methods consistently. In addition, case studies further validate the effectiveness of our proposed model in identifying novel SL pairs.AvailabilityPython codes and dataset are available at:[email protected] and [email protected]

scholarly journals Crystallization of and selenomethionine phasing strategy for a SETMAR–DNA complex

2016 ◽  
Vol 72 (9) ◽  
pp. 713-719 ◽  
Author(s):  
Qiujia Chen ◽  
Millie Georgiadis
Keyword(s):  
Dna Binding ◽  
Catalytic Domain ◽  
Specific Binding ◽  
Critical Role ◽  
Binding Activity ◽  
Structural Basis ◽  
Unexpected Finding ◽  
Terminal Inverted Repeat ◽  
Dna Binding Activity ◽  
New Genes

Transposable elements have played a critical role in the creation of new genes in all higher eukaryotes, including humans. Although the chimeric fusion protein SETMAR is no longer active as a transposase, it contains both the DNA-binding domain (DBD) and catalytic domain of theHsmar1transposase. The amino-acid sequence of the DBD has been virtually unchanged in 50 million years and, as a consequence, SETMAR retains its sequence-specific binding to the ancestralHsmar1terminal inverted repeat (TIR) sequence. Thus, the DNA-binding activity of SETMAR is likely to have an important biological function. To determine the structural basis for the recognition of TIR DNA by SETMAR, the design of TIR-containing oligonucleotides and SETMAR DBD variants, crystallization of DBD–DNA complexes, phasing strategies and initial phasing experiments are reported here. An unexpected finding was that oligonucleotides containing two BrdUs in place of thymidines produced better quality crystals in complex with SETMAR than their natural counterparts.

scholarly journals ATM loss leads to synthetic lethality in BRCA1 BRCT mutant mice associated with exacerbated defects in homology-directed repair

2017 ◽  
Vol 114 (29) ◽  
pp. 7665-7670 ◽  
Author(s):  
Chun-Chin Chen ◽  
Elizabeth M. Kass ◽  
Wei-Feng Yen ◽  
Thomas Ludwig ◽  
Mary Ellen Moynahan ◽  
...  
Keyword(s):  
Synthetic Lethality ◽  
Critical Role ◽  
Nonhomologous End Joining ◽  
Dna Double Strand Breaks ◽  
End Joining ◽  
Atm Kinase ◽  
Strand Breaks ◽  
Homology Directed Repair ◽  
Dna Damage Signaling ◽  
Mutant Cells

BRCA1 is essential for homology-directed repair (HDR) of DNA double-strand breaks in part through antagonism of the nonhomologous end-joining factor 53BP1. The ATM kinase is involved in various aspects of DNA damage signaling and repair, but how ATM participates in HDR and genetically interacts with BRCA1 in this process is unclear. To investigate this question, we used the Brca1S1598F mouse model carrying a mutation in the BRCA1 C-terminal domain of BRCA1. Whereas ATM loss leads to a mild HDR defect in adult somatic cells, we find that ATM inhibition leads to severely reduced HDR in Brca1S1598F cells. Consistent with a critical role for ATM in HDR in this background, loss of ATM leads to synthetic lethality of Brca1S1598F mice. Whereas both ATM and BRCA1 promote end resection, which can be regulated by 53BP1, 53bp1 deletion does not rescue the HDR defects of Atm mutant cells, in contrast to Brca1 mutant cells. These results demonstrate that ATM has a role in HDR independent of the BRCA1–53BP1 antagonism and that its HDR function can become critical in certain contexts.

scholarly journals Synthetic lethality screen identifies a novel yeast myosin I gene (MYO5): myosin I proteins are required for polarization of the actin cytoskeleton.

1996 ◽  
Vol 133 (6) ◽  
pp. 1277-1291 ◽  
Author(s):  
H V Goodson ◽  
B L Anderson ◽  
H M Warrick ◽  
L A Pon ◽  
J A Spudich
Keyword(s):  
Actin Cytoskeleton ◽  
Synthetic Lethality ◽  
Critical Role ◽  
Neck Region ◽  
Actin Binding ◽  
Cell Physiology ◽  
Deletion Mutants ◽  
Tail Domain ◽  
Amino Terminal ◽  
Myosin I

The organization of the actin cytoskeleton plays a critical role in cell physiology in motile and nonmotile organisms. Nonetheless, the function of the actin based motor molecules, members of the myosin superfamily, is not well understood. Deletion of MYO3, a yeast gene encoding a "classic" myosin I, has no detectable phenotype. We used a synthetic lethality screen to uncover genes whose functions might overlap with those of MYO3 and identified a second yeast myosin 1 gene, MYO5. MYO5 shows 86 and 62% identity to MYO3 across the motor and non-motor regions. Both genes contain an amino terminal motor domain, a neck region containing two IQ motifs, and a tail domain consisting of a positively charged region, a proline-rich region containing sequences implicated in ATP-insensitive actin binding, and an SH3 domain. Although myo5 deletion mutants have no detectable phenotype, yeast strains deleted for both MYO3 and MYO5 have severe defects in growth and actin cytoskeletal organization. Double deletion mutants also display phenotypes associated with actin disorganization including accumulation of intracellular membranes and vesicles, cell rounding, random bud site selection, sensitivity to high osmotic strength, and low pH as well as defects in chitin and cell wall deposition, invertase secretion, and fluid phase endocytosis. Indirect immunofluorescence studies using epitope-tagged Myo5p indicate that Myo5p is localized at actin patches. These results indicate that MYO3 and MYO5 encode classical myosin I proteins with overlapping functions and suggest a role for Myo3p and Myo5p in organization of the actin cytoskeleton of Saccharomyces cerevisiae.

Investigation of the relationships among educational application (APP) quality, computer anxiety and student engagement

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Jung-Chieh Lee ◽  
Liang Nan Xiong
Keyword(s):  
Student Engagement ◽  
Computer Anxiety ◽  
Critical Role ◽  
System Quality ◽  
Is Success ◽  
Content Type ◽  
Mediating Role ◽  
Proposed Model ◽  
Traditional Classroom Teaching ◽  
Educational Applications

PurposeNumerous educational applications (APP) have been developed to assist traditional classroom teaching and student learning. APP quality plays a critical role in influencing students' learning behaviors. However, the role negative mindsets, especially computer anxiety, play in how APP quality affects student engagement remains unknown. To address the relationships among APP quality, computer anxiety and student engagement in an APP-based learning environment, we developed an extended information system (IS) success model that includes interface and instructor quality.Design/methodology/approachTo empirically test the proposed model, we conducted a survey with a sample of 225 university students and examined the hypotheses using the partial least squares (PLS) method.FindingsComputer anxiety was demonstrated to fully mediate the relationships between student engagement and interface quality and service quality and system quality. In addition, the instructor quality acts as a partial mediator of the relationship between computer anxiety and student engagement.Originality/valueThis study reveals the important mediating role of computer anxiety in APP-assisted learning and the special status of instructor quality and user experience in influencing student engagement. The findings of this study shed meaningful light on the practical implications for instructors and APP software developers.

scholarly journals Differential gene expression, induced by salicylic acid and Fusarium oxysporum f. sp. lycopersici infection, in tomato

2008 ◽  
Vol 43 (8) ◽  
pp. 1017-1023 ◽  
Author(s):  
Daniel Oliveira Jordão do Amaral ◽  
Marleide Magalhães de Andrade Lima ◽  
Luciane Vilela Resende ◽  
Márcia Vanusa da Silva
Keyword(s):  
Salicylic Acid ◽  
Fusarium Oxysporum ◽  
Foliar Application ◽  
Cost Effective ◽  
Subtractive Hybridization ◽  
Differentially Expressed ◽  
Transcript Profile ◽  
Tomato Plants ◽  
New Genes ◽  
Differential Gene

The objective of this work was to determine the transcript profile of tomato plants (Lycopersicon esculentum Mill.), during Fusarium oxysporum f. sp. lycopersici infection and after foliar application of salicylic acid. The suppression subtractive hybridization (SSH) technique was used to generate a cDNA library enriched for transcripts differentially expressed. A total of 307 clones was identified in two subtractive libraries, which allowed the isolation of several defense-related genes that play roles in different mechanisms of plant resistance to phytopathogens. Genes with unknown roles were also isolated from the two libraries, which indicates the possibility of identifying new genes not yet reported in studies of stress/defense response. The SSH technique is effective for identification of resistance genes activated by salicylic acid and F. oxysporum f. sp. lycopersici infection. Not only the application of this technique enables a cost effective isolation of differentially expressed sequences, but also it allows the identification of novel sequences in tomato from a relative small number of sequences.

scholarly journals Rumen Sampling Methods Bias Bacterial Communities Observed

2021 ◽  
Author(s):  
Jill V. Hagey ◽  
Maia Laabs ◽  
Elizabeth A. Maga ◽  
Edward J. DePeters
Keyword(s):  
Relative Abundance ◽  
Critical Role ◽  
Cost Effective ◽  
Feed Additives ◽  
Rrna Gene ◽  
Stomach Tube ◽  
Fecal Samples ◽  
Rumen Microbes ◽  
Lower Abundance ◽  
The Family

AbstractThe rumen is a complex ecosystem that plays a critical role in our efforts to improve feed efficiency of cattle and reduce their environmental impacts. Sequencing of the 16S rRNA gene provides a powerful tool to survey shifts in the microbial community in response to feed additives and dietary changes. Oral stomach tubing a cow for a rumen sample is a rapid, cost-effective alternative to rumen cannulation for acquiring rumen samples. In this study, we determined how sampling method, as well as type of sample collected (liquid vs solid), bias the microbial populations observed. The abundance of major archaeal populations was not different at the family level in samples acquired via rumen cannula or stomach tube. Liquid samples were enriched for the order WCHB1-41 (phylum Kiritimatiellaeota) as well as the family Prevotellaceae and had significantly lower abundance of Lachnospiraceae compared with grab samples from the rumen cannula. Solid samples most closely resembled the grab samples; therefore, inclusion of particulate matter is important for an accurate representation of the rumen microbes. Stomach tube samples were the most variable and were most representative of the liquid phase. In comparison with a grab sample, stomach tube samples had significantly lower abundance of Lachnospiraceae, Fibrobacter and Treponema. Fecal samples did not reflect the community composition of the rumen, as fecal samples had significantly higher relative abundance of Ruminococcaceae and significantly lower relative abundance of Lachnospiraceae compared with samples from the rumen.

scholarly journals METHODOLOGICAL APPROACH TO CREATING A MODEL OF COST-EFFECTIVE MECHANISM FOR MANAGING INNOVATIVE ACTIVITY OF HOTEL ORGANIZATIONS

2021 ◽  
pp. 68-76
Author(s):  
T. P. Levchenko ◽  
M. B. Moldazhanov ◽  
V. V. Purichi ◽  
I. V. Strishkina
Keyword(s):  
Innovation Management ◽  
Methodological Approach ◽  
Cost Effective ◽  
Innovative Activity ◽  
Effective Management ◽  
Management Mechanism ◽  
Effective Mechanism ◽  
Scenario Modeling ◽  
Proposed Model ◽  
Activity Management

The transition of hotel organizations to a qualitatively new level of development can be ensured by the formation and use of a cost-effective innovation management mechanism. The article attempts to create a model of a cost-effective management mechanism that could take into account the multifaceted relationships of indicators and indicators of innovative activity. The operation of this mechanism implies the use of indicative control tools, as well as factor and scenario modeling. The author considers the mechanism from the perspective of implementing five interconnected blocks: subjects, goals and tasks, objects, processes and resulting effects. The content of the resulting effects of the implementation of innovative processes based on the calculation of integral indicators of innovative activity and its elements. Based on the proposed model of a cost-effective mechanism for managing the innovative activity of hotel organizations, an analysis of trends in the level of innovative activity was carried out at using the example of three hotel in Sochi, their graphical interpretation is presented. As part of the presented model, scenario modeling of innovative activity management was carried out as one of its tools, a graph of the ratio of indicators of innovative activity of hotel organizations in Sochi was built.

An analytical model for predicting noise radiated by switch reluctance electric motors

2021 ◽  
Vol 263 (2) ◽  
pp. 4100-4110
Author(s):  
Murat Inalpolat ◽  
Bahadir Sarikaya ◽  
Enes Timur Ozdemir ◽  
Hyun Ku Lee
Keyword(s):  
Magnetic Energy ◽  
Cost Effective ◽  
Torque Ripple ◽  
Air Gap ◽  
Sound Power ◽  
Electromagnetic Forces ◽  
Phase Switching ◽  
Proposed Model ◽  
Torque Ripples

Switch reluctance motors (SRM) have become a prominent alternative for electric vehicles in recent years due to their simple, high power density architecture and cost-effective manufacturability. Despite its potential, NVH problems have been one of the biggest challenges for SRM's implementation. Vibration and noise generated by the SRM are mainly caused by phase switching related torque ripple, unbalanced electromagnetic forces from air gap variations and lamination problems. Our proposed model is an analytical noise radiation prediction model which relates geometrical, material and electrical design inputs to radiated sound power. The electromagnetic part of the model is nonlinear with saturation and provides back-emf and flux linkage by receiving design inputs. The computed magnetic energy, radial and tangential rotor forces are utilized as excitation sources to a continuous shell dynamic model to obtain the steady-state vibration response. Finally, surface velocities obtained from the shell model are used to calculate sound power. Utilizing a shell structure provides axial, radial and tangential information on the casing by considering the effect of magneto-restrictive forces of laminations, torque ripples and unbalanced electromagnetic forces. The effect of air gap, lamination error, and stator and rotor geometry on sound radiation are studied through an example case study.

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