scholarly journals egKnock: identifying direct gene knockout strategies for microbial strain optimization based on metabolic network with gene-protein-reaction relationships

2019 ◽  
Author(s):  
Zixiang Xu
Keyword(s):  
Gene Deletion ◽  
Gene Knockout ◽  
Flux Variability Analysis ◽  
Variability Analysis ◽  
Direct Gene ◽  
Chemical Products ◽  
Relationship Of ◽  
Protein Reaction ◽  
Microbial Strain ◽  
Logic Relationship

AbstractBackgroundGene knockout method has been used to improve the conversion ratio of industrial strains for many chemical products. There are a series of published algorithms to predict the targets for deletion. Based on metabolic networks, many of these algorithms are designed to predict the target of reaction or enzyme deletion. But as for the many-to-many relationship between genes and reactions, reaction or enzyme deletion is not the ideal strategy for metabolic engineering. GDLS algorithm aims to find direct gene deletion target by using local search, but it actually ignores the logic relationship of gene-protein-reaction.ResultsIn this study, we aim to find direct gene deletion targets for metabolic network, but the logic relationship of gene-protein-reaction (GPR) is considered. Our algorithm is call egKnock. At the same time, egKnock will provide the solution with multiple strategies and can maximize the minimum target flux of industrial objective in flux variability analysis. We compare egKnock with the algorithm of GDLS and OptORF by predicting the targets of gene deletion for several chemical products with their flux balance analysis testification, flux variability analysis testification and the main flux distribution.ConclusionsBy comparison with the algorithm of GDLS and OptORF, we can conclude that egKnock is a nice algorithm for identifying direct gene knockout strategies for microbial strain optimization.

scholarly journals Flux variability analysis approach of autism related metabolism in stoichiometric model of mitochondria

2013 ◽  
Vol 2 (2) ◽  
pp. 37-42 ◽  
Author(s):  
Agris Pentjuss ◽  
Oskars Rubenis ◽  
Daiga Bauze ◽  
Lilija Aprupe ◽  
Baiba Lace
Keyword(s):  
Analysis Approach ◽  
Flux Variability Analysis ◽  
Variability Analysis ◽  
Stoichiometric Model ◽  
Flux Variability

scholarly journals MicroRNA and circRNA Expression Analysis in a Zbtb1 Gene Knockout Monoclonal EL4 Cell Line

2021 ◽  
Vol 11 ◽  
Author(s):  
Jun-Hong Wang ◽  
Chun-Wei Shi ◽  
Yi-Yuan Lu ◽  
Yan Zeng ◽  
Ming-Yang Cheng ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Line ◽  
Gene Deletion ◽  
Cell Lymphoma ◽  
Gene Knockout ◽  
Expression Profiles ◽  
T Cell Lymphoma ◽  
Differentially Expressed ◽  
Btb Domain

Zinc finger and BTB domain containing 1(Zbtb1) is a transcriptional suppressor protein, and a member of the mammalian Zbtb gene family. Previous studies have shown that Zbtb1 is essential for T-cell development. However, the role of Zbtb1 in T-cell lymphoma is undetermined. In this study, an EL4 cell line with Zbtb1 deletion was constructed using the CRISPR-Cas9 technique. The expression profiles of microRNA and circRNA produced by the control and gene deletion groups were determined by RNA-seq. In general, 24 differentially expressed microRNA and 16 differentially expressed circRNA were found between normal group and gene deletion group. Through further analysis of differentially expressed genes, GO term histogram and KEGG scatter plot were drawn, and three pairs of miRNA and circRNA regulatory relationships were found. This study describes the differentially expressed microRNA and circRNA in normal and Zbtb1-deficient EL4 cell lines, thus providing potential targets for drug development and clinical treatment of T-cell lymphoma.

Abstract 311: Poly(ADP-ribose) Polymerase-1 Inhibition Prevents High Fat Diet-induced Cardiac Hypertrophy by Modulating Matrix-destabilizing Proteases and Oxidative Stress

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Chetan P Hans ◽  
Yumei Feng ◽  
Amarjit Naura ◽  
Mourad Zerfaoui ◽  
Dana Troxclair ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Cardiac Myocytes ◽  
High Fat Diet ◽  
Gene Deletion ◽  
Structural Integrity ◽  
Imaging System ◽  
Gene Knockout ◽  
Hemodynamic Parameters ◽  
High Fat ◽  
Parp 1

Background: We recently showed that PARP-1 is activated within atherosclerotic plaques and that inhibition of this enzyme, exerts protective effects against high fat diet-induced atherogenesis. Given the tight association between atherosclerosis and cardiac pathologies, we examined, whether PARP-1 is an active participant in high fat diet-induced cardiac hypertrophy and whether PARP-1 gene knockout prevents such pathological abnormalities. Methods: Apolipoprotein (ApoE)−/− mice fed a high-fat diet were used as a model of atherosclerosis. C57BL/6 ApoE−/− mice that are deficient in PARP-1 (ApoE-PARP-1d−/−) were generated in our laboratory. Hemodynamic parameters were obtained by a small animal-adapted ultrasound imaging system. Results: Hemodynamic parameters revealed that ApoE−/− mice on regular diet exhibited markers of cardiac hypertrophy. PARP-1 gene knockout markedly protected against dyslipidemia-induced cardiac hypertrophy. An increase in dyslipidemia burden further exacerbated the latter parameters in ApoE−/− mice. Inhibition of PARP-1 by gene deletion provided a significant protection against the parameters of cardiac hypertrophy. Histology showed enlarged hypertrophied cardiac myocytes in ApoE−/− mice with typical “boxcar-shaped” nuclei and high-fat diet caused separation of the myocardial fibers suggestive of dilated cardiomyopathy in these mice. PARP-1 gene deletion maintained the structural integrity of cardiac myocytes. MMP activity, measured by zymography, was dramatically increased in heart and aorta of ApoE−/− mice on high-fat diet compared to ApoE-PARP-1d−/− mice on similar diet regimen, which was accompanied by increased collagen degradation and mast cell degranulation. PARP-1 gene knockout was associated with increased TIMP-2 expression in various cells of vascular origin which seemed to neutralize the degenerative effects of MMP activity. Discussion: Our results demonstrate that PARP-1 gene deletion protects against dyslipidemia-induced cardiac hypertrophy and dilatations. We also provide evidence that PARP-1 inhibition protects against these pathologies by increasing expression of TIMP-2 and subsequent inhibition of tissue-degrading proteases in a mouse model of atherosclerosis.

scholarly journals Poly(Beta-Amino Ester) Nanoparticles Enable Nonviral Delivery of CRISPR-Cas9 Plasmids for Gene Knockout and Gene Deletion

2020 ◽  
Vol 20 ◽  
pp. 661-672 ◽  
Author(s):  
Yuan Rui ◽  
Mahita Varanasi ◽  
Shanelle Mendes ◽  
Hannah M. Yamagata ◽  
David R. Wilson ◽  
...  
Keyword(s):  
Gene Deletion ◽  
Gene Knockout ◽  
Amino Ester ◽  
Nonviral Delivery

scholarly journals Adaptive Flux Variability Analysis: A Tool To Deal With Uncertainties

2019 ◽  
Vol 52 (1) ◽  
pp. 70-75 ◽  
Author(s):  
T. Abbate ◽  
L. Dewasme ◽  
Ph. Bogaerts ◽  
A. Vande Wouwer
Keyword(s):  
Flux Variability Analysis ◽  
Variability Analysis ◽  
Flux Variability

scholarly journals Long Term UV Continuum and Line Variability in NGC 1275

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Bryan Rithesh Miranda ◽  
Vijayakumar H Doddamani ◽  
Vedavathi P
Keyword(s):  
Emission Line ◽  
Spectroscopic Data ◽  
Wavelength Region ◽  
Emission Lines ◽  
Observational Period ◽  
Flux Variability Analysis ◽  
Variability Analysis ◽  
Ngc 1275 ◽  
First Time

In this paper, we present our results for the first time on long term emission-line and continuum variability studies using the International Ultraviolet Explorer’s final archive of UV spectroscopic data obtained in the wavelength region from 1150 Å to 3200 Å for NGC 1275, a dust dominated BL Lac characterized by the Rmax and  F-variance parameter. The UV continuum flux variability analysis presented in this paper covers more number of emission-line free continuum windows in the UV region centred at  1710 Å, 1800 Å, 2625 Å, 2875 Å & 3025 Å. We have obtained a higher value of Fvar  ~ 45 % at 1710 Å and a lower value of ~ 30 % at 1800 Å for the IUE's observational period of 1978 - 1989. The Lyα, C IV, C III] and Mg II emission lines have been observed as weaker line features on fewer occasions intermittently.

scholarly journals 6S-1 RNA Contributes to Sporulation and Parasporal Crystal Formation in Bacillus thuringiensis

2020 ◽  
Vol 11 ◽  
Author(s):  
Zhou Li ◽  
Li Zhu ◽  
Zhaoqing Yu ◽  
Lu Liu ◽  
Shan-Ho Chou ◽  
...  
Keyword(s):  
Bacillus Thuringiensis ◽  
Deletion Mutant ◽  
Gene Deletion ◽  
Gene Knockout ◽  
Single Gene ◽  
Crystal Formation ◽  
Bacterial Cells ◽  
Parasporal Crystal ◽  
6S Rna ◽  
Gene Deletion Mutant

6S RNA is a kind of high-abundance non-coding RNA that globally regulates bacterial transcription by interacting with RNA polymerase holoenzyme. Through bioinformatics analysis, we found that there are two tandem 6S RNA-encoding genes in the genomes of Bacillus cereus group bacteria. Using Bacillus thuringiensis BMB171 as the starting strain, we have explored the physiological functions of 6S RNAs, and found that the genes ssrSA and ssrSB encoding 6S-1 and 6S-2 RNAs were located in the same operon and are co-transcribed as a precursor that might be processed by specific ribonucleases to form mature 6S-1 and 6S-2 RNAs. We also constructed two single-gene deletion mutant strains ΔssrSA and ΔssrSB and a double-gene deletion mutant strain ΔssrSAB by means of the markerless gene knockout method. Our data show that deletion of 6S-1 RNA inhibited the growth of B. thuringiensis in the stationary phase, leading to lysis of some bacterial cells. Furthermore, deletion of 6S-1 RNA also significantly reduced the spore number and parasporal crystal content. Our work reveals that B. thuringiensis 6S RNA played an important regulatory role in ensuring the sporulation and parasporal crystal formation.

scholarly journals VFFVA: dynamic load balancing enables large-scale flux variability analysis

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Marouen Ben Guebila
Keyword(s):  
Load Balancing ◽  
Large Scale ◽  
Parallel Implementation ◽  
Convergence Time ◽  
Coupled Models ◽  
Flux Variability Analysis ◽  
Variability Analysis ◽  
Flux Variability ◽  
Fast Flux ◽  
Computation Load

Abstract Background Genome-scale metabolic models are increasingly employed to predict the phenotype of various biological systems pertaining to healthcare and bioengineering. To characterize the full metabolic spectrum of such systems, Fast Flux Variability Analysis (FFVA) is commonly used in parallel with static load balancing. This approach assigns to each core an equal number of biochemical reactions without consideration of their solution complexity. Results Here, we present Very Fast Flux Variability Analysis (VFFVA) as a parallel implementation that dynamically balances the computation load between the cores in runtime which guarantees equal convergence time between them. VFFVA allowed to gain a threefold speedup factor with coupled models and up to 100 with ill-conditioned models along with a 14-fold decrease in memory usage. Conclusions VFFVA exploits the parallel capabilities of modern machines to enable biological insights through optimizing systems biology modeling. VFFVA is available in C, MATLAB, and Python at https://github.com/marouenbg/VFFVA.

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