scholarly journals Identification of Most Lethal Non-synonymous SNPs in Tollip gene- An In-Silico Analysis

2021 ◽  
Author(s):  
Usman Ghani ◽  
Rahmat Ullah ◽  
Tayyaba Anjum ◽  
Yasir Ali ◽  
Muhammad Farooq Sabar ◽  
...  
Keyword(s):  
Membrane Trafficking ◽  
In Silico ◽  
Interleukin 1 ◽  
Intracellular Localization ◽  
In Silico Analysis ◽  
Gene Interaction ◽  
Intestinal Epithelial ◽  
Interacting Protein ◽  
Synonymous Snps ◽  
Wide Range

Abstract The Toll-interacting protein (TOLLIP), first detected by hybrid screening using Interleukin-1 receptor accessory protein in 2000, is ubiquitous and its TLR signaling cascade gets negatively regulated by TOLLIP in particular by impeding the TLR4 and TLR2 pathways. Toll-interacting protein facilitates TLR and TGF-β type 1 receptor intracellular localization and lysosomal degradation and exerts its anti-apoptosis and pro-autophagy effects through interaction with a target of Myb1 membrane trafficking protein 1 (TOM1) in autoimmunity. It also protects intestinal epithelial cells from apoptosis induced by (TNF-α) (IFN-γ) signaling and acts as a cargo adaptor linking (ATG8) autophagy gene 8 and microtubule-associated protein 1 light chain 3. Ubiquitin-modified cell debris along with coated autophagosomes removes harmful protein aggregates and maintains cellular homeostasis. It is therefore structurally and functionally important to detect TOLLIP polymorphisms to indicate the possible malfunctions and therapeutics. We have identified the gap of available data on nsSNPs in the TOLLIP gene in previous studies. Hence, We have used a wide range of bioinformatic techniques in this study to identify the most destructive nsSNPs in the TOLLIP gene. The in-silico tools such as PROVEAN, SIFT, SNP&GO, PhD SNP, and PolyPhen2 have been used followed by I Mutant, MutPred, and ConSurf. The 3-D mapping was carried out with I-TASSER and Phyre2. Though, STRING and GeneMANIA proposed the gene to gene interaction of TOLLIP. Our study identified G19D (rs866744102), G32R (rs1308704061), D71N (rs777772934), and E72G (rs1202660177) as the four most lethal non-synonymous SNPs in TOLLIP genes, which may play an essential part in defects of TOLLIP Protein and probably cause a different type of diseases. This is the first study of its kind, and it could pave the way in the field of medical drugs in the future. The influence of these nsSNPs in the normal functioning of TOLLIP can also be evaluated in animal models to identify the underlying biochemical pathway involved in diseases.

scholarly journals Identification of Most Lethal Non-synonymous SNPs in Tollip gene- An In-Silico Analysis

2021 ◽  
Author(s):  
Usman Ghani ◽  
Rahmat Ullah ◽  
Sadia Anjum ◽  
Yasir Ali ◽  
Saddam Hussain ◽  
...  
Keyword(s):  
Membrane Trafficking ◽  
In Silico ◽  
Interleukin 1 ◽  
Intracellular Localization ◽  
In Silico Analysis ◽  
Gene Interaction ◽  
Intestinal Epithelial ◽  
Interacting Protein ◽  
Synonymous Snps ◽  
Wide Range

Abstract The Toll-interacting protein (TOLLIP), first detected by hybrid screening using Interleukin-1 receptor accessory protein in 2000, is ubiquitous and its TLR signaling cascade gets negatively regulated by TOLLIP in particular by impeding the TLR4 and TLR2 pathways. Toll-interacting protein facilitates TLR and TGF-β type 1 receptor intracellular localization and lysosomal degradation and exerts its anti-apoptosis and pro-autophagy effects through interaction with a target of Myb1 membrane trafficking protein 1 (TOM1) in autoimmunity. It also protects intestinal epithelial cells from apoptosis induced by (TNF-α) (IFN-γ) signaling and acts as a cargo adaptor linking (ATG8) autophagy gene 8 and microtubule-associated protein 1 light chain 3. Ubiquitin-modified cell debris along with coated autophagosomes removes harmful protein aggregates and maintains cellular homeostasis. It is therefore structurally and functionally important to detect TOLLIP polymorphisms to indicate the possible malfunctions and therapeutics. We have identified the gap of available data on nsSNPs in the TOLLIP gene in previous studies. Hence, We have used a wide range of bioinformatic techniques in this study to identify the most destructive nsSNPs in the TOLLIP gene. The in-silico tools such as PROVEAN, SIFT, SNP&GO, PhD SNP, and PolyPhen2 have been used followed by I Mutant, MutPred, and ConSurf. The 3-D mapping was carried out with I-TASSER and Phyre2. Though, STRING and GeneMANIA proposed the gene to gene interaction of TOLLIP. Our study identified G19D (rs866744102), G32R (rs1308704061), D71N (rs777772934), and E72G (rs1202660177) as the four most lethal non-synonymous SNPs in TOLLIP genes, which may play an essential part in defects of TOLLIP Protein and probably cause a different type of diseases. This is the first study of its kind, and it could pave the way in the field of medical drugs in the future. The influence of these nsSNPs in the normal functioning of TOLLIP can also be evaluated in animal models to identify the underlying biochemical pathway involved in diseases.

scholarly journals Identification of Most Lethal Non-synonymous SNPs in Tollip gene- An In-Silico Analysis

2021 ◽  
Author(s):  
Usman Ghani ◽  
Rahmat Ullah ◽  
Tayyaba Anjum ◽  
Yasir Ali ◽  
Saddam Hussain ◽  
...  
Keyword(s):  
Membrane Trafficking ◽  
In Silico ◽  
Interleukin 1 ◽  
Intracellular Localization ◽  
In Silico Analysis ◽  
Gene Interaction ◽  
Intestinal Epithelial ◽  
Interacting Protein ◽  
Synonymous Snps ◽  
Wide Range

Abstract The Toll-interacting protein (TOLLIP), first detected by hybrid screening using Interleukin-1 receptor accessory protein in 2000, is ubiquitous and its TLR signaling cascade gets negatively regulated by TOLLIP in particular by impeding the TLR4 and TLR2 pathways. Toll-interacting protein facilitates TLR and TGF-β type 1 receptor intracellular localization and lysosomal degradation and exerts its anti-apoptosis and pro-autophagy effects through interaction with a target of Myb1 membrane trafficking protein 1 (TOM1) in autoimmunity. It also protects intestinal epithelial cells from apoptosis induced by (TNF-α) (IFN-γ) signaling and acts as a cargo adaptor linking (ATG8) autophagy gene 8 and microtubule-associated protein 1 light chain 3. Ubiquitin-modified cell debris along with coated autophagosomes removes harmful protein aggregates and maintains cellular homeostasis. It is therefore structurally and functionally important to detect TOLLIP polymorphisms to indicate the possible malfunctions and therapeutics. We have identified the gap of available data on nsSNPs in the TOLLIP gene in previous studies. Hence, We have used a wide range of bioinformatic techniques in this study to identify the most destructive nsSNPs in the TOLLIP gene. The in-silico tools such as PROVEAN, SIFT, SNP&GO, PhD SNP, and PolyPhen2 have been used followed by I Mutant, MutPred, and ConSurf. The 3-D mapping was carried out with I-TASSER and Phyre2. Though, STRING and GeneMANIA proposed the gene to gene interaction of TOLLIP. Our study identified G19D (rs866744102), G32R (rs1308704061), D71N (rs777772934), and E72G (rs1202660177) as the four most lethal non-synonymous SNPs in TOLLIP genes, which may play an essential part in defects of TOLLIP Protein and probably cause a different type of diseases. This is the first study of its kind, and it could pave the way in the field of medical drugs in the future. The influence of these nsSNPs in the normal functioning of TOLLIP can also be evaluated in animal models to identify the underlying biochemical pathway involved in diseases.

scholarly journals Identification of Most Lethal Non-synonymous SNPs in Tollip gene- An In-Silico Analysis

2021 ◽  
Author(s):  
Usman Ghani ◽  
Rahmat Ullah ◽  
Tayyaba Anjum ◽  
Yasir Ali ◽  
Muhammad Farooq Sabar ◽  
...  
Keyword(s):  
Membrane Trafficking ◽  
In Silico ◽  
Interleukin 1 ◽  
Intracellular Localization ◽  
In Silico Analysis ◽  
Gene Interaction ◽  
Intestinal Epithelial ◽  
Interacting Protein ◽  
Synonymous Snps ◽  
Wide Range

Abstract The Toll-interacting protein (TOLLIP), first detected by hybrid screening using Interleukin-1 receptor accessory protein in 2000, is ubiquitous and its TLR signaling cascade gets negatively regulated by TOLLIP in particular by impeding the TLR4 and TLR2 pathways. Toll-interacting protein facilitates TLR and TGF-β type 1 receptor intracellular localization and lysosomal degradation and exerts its anti-apoptosis and pro-autophagy effects through interaction with a target of Myb1 membrane trafficking protein 1 (TOM1) in autoimmunity. It also protects intestinal epithelial cells from apoptosis induced by (TNF-α) (IFN-γ) signaling and acts as a cargo adaptor linking (ATG8) autophagy gene 8 and microtubule-associated protein 1 light chain 3. Ubiquitin-modified cell debris along with coated autophagosomes removes harmful protein aggregates and maintains cellular homeostasis. It is therefore structurally and functionally important to detect TOLLIP polymorphisms to indicate the possible malfunctions and therapeutics. We have identified the gap of available data on nsSNPs in the TOLLIP gene in previous studies. Hence, We have used a wide range of bioinformatic techniques in this study to identify the most destructive nsSNPs in the TOLLIP gene. The in-silico tools such as PROVEAN, SIFT, SNP&GO, PhD SNP, and PolyPhen2 have been used followed by I Mutant, MutPred, and ConSurf. The 3-D mapping was carried out with I-TASSER and Phyre2. Though, STRING and GeneMANIA proposed the gene to gene interaction of TOLLIP. Our study identified G19D (rs866744102), G32R (rs1308704061), D71N (rs777772934), and E72G (rs1202660177) as the four most lethal non-synonymous SNPs in TOLLIP genes, which may play an essential part in defects of TOLLIP Protein and probably cause a different type of diseases. This is the first study of its kind, and it could pave the way in the field of medical drugs in the future. The influence of these nsSNPs in the normal functioning of TOLLIP can also be evaluated in animal models to identify the underlying biochemical pathway involved in diseases.

In-silico analysis of non- synonymous SNPs of human LDLR gene and their impact on familial hypercholesterolemia

Gene Reports ◽  
2021 ◽  
pp. 101127
Author(s):  
Pratik Ghosh ◽  
Samarpita Ghosh ◽  
Bhaskar Behera ◽  
Jiban Kumar Behera ◽  
Manojit Bhattacharya ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
In Silico ◽  
In Silico Analysis ◽  
Ldlr Gene ◽  
Synonymous Snps ◽  
Silico Analysis

scholarly journals Drug-disease interactions of differentially expressed genes in COVID-19 liver samples: an in-silico analysis

2021 ◽  
Vol 62 (4) ◽  
pp. 316-324
Author(s):  
Susan Omar Rasool ◽  
Ata Mirzaei Nahr ◽  
Sania Eskandari ◽  
Milad Hosseinzadeh ◽  
Soheila Asoudeh Moghanloo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cytochrome P450 ◽  
Differentially Expressed Genes ◽  
In Silico ◽  
In Silico Analysis ◽  
Gene Interaction ◽  
Differentially Expressed ◽  
Alcoholic Fatty Liver ◽  
Interaction Database ◽  
Cytochrome P450 Genes

While COVID-19 liver injuries have been reported in various studies, concerns are raised about disease-drug reactions in COVID-19 patients. In this study, we examined the hypothesis of gene-disease interactions in an in-silico model of gene expression to seek changes in cytochrome P450 genes. The Gene Expression Omnibus dataset of the liver autopsy in deceased COVID-19 patients (GSE150316) was used in this study. Non-alcoholic fatty liver biopsies were used as the control (GSE167523). Besides, gene expression analysis was performed using the DESeq/EdgeR method. The GO databases were used, and the paths were set at p<0.05. The drug-gene interaction database (DGIdb) was searched for interactions. According to the results, 5,147 genes were downregulated, and 5,122 genes were upregulated in SARS-CoV-2 compared to healthy livers. Compared to the cytochromes, 34 cytochromes were downregulated, while 4 cytochromes were upregulated among the detected differentially expressed genes (DEG). The drug-gene interaction database (DGIdb) provided a list of medications with potential interactions with COVID-19 as well as metacetamol, phenethyl isocyanate, amodiaquine, spironolactone, amiloride, acenocoumarol, clopidogrel, phenprocoumon, trimipramine, phenazepam, etc. Besides, dietary compounds of isoflavones, valerian, and coumarin, as well as caffeine metabolism were shown to have possible interactions with COVID-19 disease. Our study showed that expression levels of cytochrome P450 genes could get altered following COVID-19. In addition, a drug-disease interaction list is recommended to be used for evaluations in clinical considerations in further studies.

scholarly journals Comprehensive In Silico Analysis and Transcriptional Profiles Highlight the Importance of Mitochondrial Dicarboxylate Carriers (DICs) on Hypoxia Response in Both Arabidopsis thaliana and Eucalyptus grandis

Plants ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 181
Author(s):  
Pedro Barreto ◽  
Mariana L. C. Arcuri ◽  
Rômulo Pedro Macêdo Lima ◽  
Celso Luis Marino ◽  
Ivan G. Maia
Keyword(s):  
In Silico ◽  
Seedling Survival ◽  
Expression Patterns ◽  
Eucalyptus Grandis ◽  
In Silico Analysis ◽  
Developmental Expression ◽  
Hypoxia Response ◽  
Submergence Stress ◽  
Wide Range ◽  
Silico Analysis

Plant dicarboxylate carriers (DICs) transport a wide range of dicarboxylates across the mitochondrial inner membrane. The Arabidopsis thalianaDIC family is composed of three genes (AtDIC1, 2 and 3), whereas two genes (EgDIC1 and EgDIC2) have been retrieved in Eucalyptus grandis. Here, by combining in silico and in planta analyses, we provide evidence that DICs are partially redundant, important in plant adaptation to environmental stresses and part of a low-oxygen response in both species. AtDIC1 and AtDIC2 are present in most plant species and have very similar gene structure, developmental expression patterns and absolute expression across natural Arabidopsis accessions. In contrast, AtDIC3 seems to be an early genome acquisition found in Brassicaceae and shows relatively low (or no) expression across these accessions. In silico analysis revealed that both AtDICs and EgDICs are highly responsive to stresses, especially to cold and submergence, while their promoters are enriched for stress-responsive transcription factors binding sites. The expression of AtDIC1 and AtDIC2 is highly correlated across natural accessions and in response to stresses, while no correlation was found for AtDIC3. Gene ontology enrichment analysis suggests a role for AtDIC1 and AtDIC2 in response to hypoxia, and for AtDIC3 in phosphate starvation. Accordingly, the investigated genes are induced by submergence stress in A. thaliana and E. grandis while AtDIC2 overexpression improved seedling survival to submergence. Interestingly, the induction of AtDIC1 and AtDIC2 is abrogated in the erfVII mutant that is devoid of plant oxygen sensing, suggesting that these genes are part of a conserved hypoxia response in Arabidopsis.

scholarly journals In Silico Analysis of Laccifer Lacca as a Potential Therapeutic Agent for Cervical, Breast and Lung Cancers

2021 ◽  
Vol 11 (3) ◽  
pp. 79-85
Author(s):  
Ashish Kumar ◽  
Neeraj Kumar ◽  
Balwan Singh
Keyword(s):  
Nitric Oxide ◽  
Molecular Docking ◽  
In Silico ◽  
A549 Cells ◽  
In Silico Analysis ◽  
Wide Range ◽  
Anticancer Therapeutics ◽  
Anti Inflammatory ◽  
Silico Analysis

Laccifer lacca has generally been used as pigmenting, coloring agent and dying in chemical industry. Although, it has wide range of industrial applications, but inappropriately, due to lesser availability of data, it has been ignored. Keeping in mind, the wide application of Laccifer lacca, we tried to report the in-silico anti-cancer effects. The experimental techniques used to determine the structure was X-RAY diffraction. The reported resolution of this entry is 2.80 Å. Percentile scores (ranging between 0-100) for global authentication metrics of the record. In silico have a good pool to explore various parameters in molecular docking. We have performed in silico analysis of the active components of Laccifer lacca against the cervical, breast and lung cancer proteins and also found that lac extract enhances the production of anti-inflammatory markers and the increase is significant when compared to the standard vinblastine. It has been demonstrated by Lala and colleagues that a short lived molecule nitric oxide can result in the progression of human tumours. Therefore, the prominent antioxidant activity of phytochemical that can act as inhibitors of nitric oxide production can act as anticancer therapeutics. Both methanolic and aqueous extract shows significant anticancer effect on the hela, MCF-7 & A549 cells suggesting them as potential anticancer therapeutics for future. Keywords: Laccifer lacca, In-vitro & In-silico analysis, Carcinogenesis, Anti-inflammatory, Molecular Docking.

scholarly journals TOR represses stress responses through global regulation of H3K27 trimethylation in plants

2021 ◽  
Author(s):  
Yihan Dong ◽  
Veli Vural Uslu ◽  
Alexandre Berr ◽  
Gaurav Singh ◽  
Csaba Papdi ◽  
...  
Keyword(s):  
Stress Responses ◽  
In Silico ◽  
In Silico Analysis ◽  
Tor Signaling ◽  
Chromatin Domains ◽  
Transcriptional Reprogramming ◽  
Wide Range ◽  
High Level ◽  
External Stimuli

Combinations of epigenetic modifications H3K4me3 and H3K27me3 implicate bistable feature which alternates between on and off state allowing rapid transcriptional changes upon external stimuli. Target of Rapamycin (TOR) functions as a central sensory hub to link a wide range of external stimuli to gene expression. However, the mechanisms underlying stimulus-specific transcriptional reprogramming by TOR remains elusive. Our in silico analysis in Arabidopsis demonstrates that TOR-repressed genes are associated with either bistable or silent chromatin domains. Both domains regulated by TOR signaling pathway are associated with high level of H3K27me3 deposited by CURLY LEAF (CLF) in specific context with LIKE HETEROCHROMATIN PROTEIN1 (LHP1). Chromatin remodeler SWI2/SNF2 ATPase BRAHMA (BRM) activates TOR-repressed genes only at bistable chromatin domains to rapidly induce biotic stress responses. Here we demonstrated both in silico and in vivo that TOR represses transcriptional stress responses through global maintenance of H3K27me3.

scholarly journals TRIM24-RIP3 axis perturbation accelerates osteoarthritis pathogenesis

2020 ◽  
Vol 79 (12) ◽  
pp. 1635-1643
Author(s):  
Jimin Jeon ◽  
Hyun-Jin Noh ◽  
Hyemi Lee ◽  
Han-Hee Park ◽  
Yu-Jin Ha ◽  
...  
Keyword(s):  
In Silico ◽  
Target Gene ◽  
Kinase Activity ◽  
Medial Meniscus ◽  
In Silico Analysis ◽  
Negative Regulator ◽  
Wild Type ◽  
Interacting Protein ◽  
Silico Analysis

ObjectivesRecently, necroptosis has attracted increasing attention in arthritis research; however, it remains unclear whether its regulation is involved in osteoarthritis (OA) pathogenesis. Since receptor-interacting protein kinase-3 (RIP3) plays a pivotal role in necroptosis and its dysregulation is involved in various pathological processes, we investigated the role of the RIP3 axis in OA pathogenesis.MethodsExperimental OA was induced in wild-type or Rip3 knockout mice by surgery to destabilise the medial meniscus (DMM) or the intra-articular injection of adenovirus carrying a target gene (Ad-Rip3 and Ad-Trim24 shRNA). RIP3 expression was examined in OA cartilage from human patients; Trim24, a negative regulator of RIP3, was identified by microarray and in silico analysis. Connectivity map (CMap) and in silico binding approaches were used to identify RIP3 inhibitors and to examine their direct regulation of RIP3 activation in OA pathogenesis.ResultsRIP3 expression was markedly higher in damaged cartilage from patients with OA than in undamaged cartilage. In the mouse model, adenoviral RIP3 overexpression accelerated cartilage disruption, whereas Rip3 depletion reduced DMM-induced OA pathogenesis. Additionally, TRIM24 knockdown upregulated RIP3 expression; its downregulation promoted OA pathogenesis in knee joint tissues. The CMap approach and in silico binding assay identified AZ-628 as a potent RIP3 inhibitor and demonstrated that it abolished RIP3-mediated OA pathogenesis by inhibiting RIP3 kinase activity.ConclusionsTRIM24-RIP3 axis perturbation promotes OA chronicity by activating RIP3 kinase, suggesting that the therapeutic manipulation of this pathway could provide new avenues for treating OA.

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