Biology subjects

Abdelmoneim, A. H.

Publications and source records attributed to Abdelmoneim, A. H..

15 recordsLinked to original sources

bioRxiv2021

Design of Epitope Based Peptide Vaccine against Brucella Abortus OmpW Family Protein using Immunoinformatics

Brucella abortus is a small aerobic, non-spore-forming, non-motile intracellular coccobacilli localized in the reproductive organs of host animals and causes acute or chronic disorders. It infects approximately 200 cases per 100,000 of the population and has become endemic in many countries. OmpW family protein is an outer membrane protein involved in the initial interaction between the pathogen and its host. This study predicts an effective epitope-based vaccine against OmpW family protein of Brucella abortus using immunoinformatics tools. Sequences were obtained from NCBI and prediction tests were accomplished to analyze possible epitopes for B and T cells. Seven B cell epitopes passed the antigenicity, accessibility and hydrophilicity tests. Forty-three MHC I epitopes were the most promising, while 438 from MHC II. For the population coverage, the epitopes covered 99.97% of the alleles worldwide excluding certain MHC II alleles. We recommend invivo and invitro studies to prove its effectiveness.

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bioRxiv2020

Bio-informatic Analysis of Missense Single Nucleotide Polymorphisms (SNPs) in Human CD38 Gene Associated with B-Chronic Lymphocytic Leukemia

BackgroundCLL: Chronic lymphocytic leukemia is a chronic type of haematological malignancies that evoked from lymph proliferative origin of bone marrow and secondary lymphoid tissue, resultant in proliferation and progressive accumulation of distinct monoclonal CD5 /CD19 /CD23 B lymphocytes in the bone marrow, peripheral blood, and lymphatic organs. CD38 is a multifunctional ecto-enzyme, known to be a direct contributor in pathogenesis of CLL by poorly understood mechanism. Even though, it highly expressed in CLL. At specific position of CD38 gene sequence, substitution of single nucleotide may result in change in amino acid that ends by consequent alteration of protein structure. AimTo study CD38 polymorphism and to predict its effect on structure and subsequently function of CD38 molecule. Methodology and ResultThe bioinformatic analysis of CD38 gene had been carried out by using several soft wares. Functional analysis by SIFT, Polyphen2, and PROVEAN reveled 12 deleterious SNPs. These SNPs were further analyzed by SNAP2, SNP@GO. PMut, STRING and other soft wars. Furthermore, Stability analysis was done using I-Mutant and MUpro software where seven SNPs were found to decrease the stability of the protein by I-Mutant, while two SNPs increase it. At the same time, eight SNPs were found to decrease the stability by Mupro software while only one SNP is predicted to increase it. Finally, Physiochemical analysis was done using Project Hope. ConclusionIn summary, CD38 genotype seems to have twelve SNP that possibly will result in deleterious effect on Protein Structure. This genetic variation eventually will lead to alteration in potential molecule functions. Which effect the progression of CLL By the end.

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bioRxiv2020

In silico multi-epitope vaccine against covid19 showing effective interaction with HLA-B*15:03

The recent outbreak of severe acute respiratory syndrome (SARS) coronavirus (CoV)-2 (SARS-CoV-2) causing coronavirus disease (covid19) has posed a great threat to human health. Previous outbreaks of SARS-CoV and Middle East respiratory Syndrome CoV (MERS-CoV) from the same CoV family had posed similar threat to human health and economic growth. To date, not even a single drug specific to any of these CoVs has been developed nor any anti-viral vaccine is available for the treatment of diseases caused by CoVs. Subunits present in spike glycoproteins of SARS-CoV and SARS-CoV-2 are involved in binding to human ACE2 Receptor which is the primary method of viral invasion. As it has been observed in the previous studies that there are very minor differences in the spike glycoproteins of SARS-CoV and SARS-CoV-2. SARS-CoV-2 has an additional furin cleavage site that makes it different from SARS-CoV (Walls et al., 2020). In this study, we have analyzed spike glycoproteins of SARS-CoV-2 and SARS-CoV phylogenetically and subjected them to selection pressure analysis. Selection pressure analysis has revealed some important sites in SARS-CoV-2 and SARS-CoV spike glycoproteins that might be involved in their pathogenicity. Further, we have developed a potential multi-epitope vaccine candidate against SARS-CoV-2 by analyzing its interactions with HLA-B*15:03 subtype. This vaccine consists of multiple T-helper (TH) cells, B-cells, and Cytotoxic T-cells (CTL) epitopes joined by linkers and an adjuvant to increase its immunogenicity. Conservation of selected epitopes in SARS, MERS, and human hosts, suggests that the designed vaccine could provide cross-protection. The vaccine is designed in silico by following a reverse vaccinology method acknowledging its antigenicity, immunogenicity, toxicity, and allergenicity. The vaccine candidate that we have designed as a result of this work shows promising result indicating its potential capability of simulating an immune response.

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bioRxiv2020

Extensive In Silico Analysis of the Functional and Structural Consequences of SNPs in Human ARX Gene

Early infantile epileptic encephalopathy 1 (EIEE1) is a rare but devastating neurologic disorder that displays concomitant cognitive and motor impairment, and is often presented in the first months of life with severe intellectual disability. The objective of this study is to classify the most deleterious nsSNPs in ARX gene that may cause EIEE1 disease. Despite the reported association of ARX gene mutations with vulnerability to several neurologic condition, there is lack of in silico analysis on the functional and structural impacts of single nucleotide polymorphisms (SNPs) of the ARX at protein level. Therefore, the pathogenic nsSNPs in the human ARX obtained from NCBI were analyzed for their functional and structural impact using bioinformatics tools like SIFT, Polyphen, PROVEAN, I-Mutant, and MUPro. The effects of the mutations on tertiary structure of the human ARX protein were predicted using RaptorX and visualized by UCSF Chimera while STRING was used to investigate its protein-protein interaction. Our extensive in silico analysis revealed 11 mutations that will significantly alter the structure of human ARX protein; that may disturb the domain which will affect the function of the protein. Extensive in silico analysis of the functional and structural consequences of SNPs in human ARX gene revealed 11 mutations (L535Q, R528S, R380L, V374D, L343Q, T333N, T333S, R332H, R330H, G34R and L33P) that may cause EIEE1.Therefore, can be used as diagnostic markers for EIEE1.

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bioRxiv2020

Design of multi epitope-based peptide vaccine against E protein of human 2019-nCoV: An immunoinformatics approach

BackgroundNew endemic disease has been spread across Wuhan City, China on December 2019. Within few weeks, the World Health Organization (WHO) announced a novel coronavirus designated as coronavirus disease 2019 (COVID-19). In late January 2020, WHO declared the outbreak of a "public-health emergency of international concern" due to the rapid and increasing spread of the disease worldwide. Currently, there is no vaccine or approved treatment for this emerging infection; thus the objective of this study is to design a multi epitope peptide vaccine against COVID-19 using immunoinformatics approach. MethodSeveral techniques facilitating the combination of immunoinformatics approach and comparative genomic approach were used in order to determine the potential peptides for designing the T cell epitopes-based peptide vaccine using the envelope protein of 2019-nCoV as a target. ResultsExtensive mutations, insertion and deletion were discovered with comparative sequencing in COVID-19 strain. Additionally, ten peptides binding to MHC class I and MHC class II were found to be promising candidates for vaccine design with adequate world population coverage of 88.5% and 99.99%, respectively. ConclusionT cell epitopes-based peptide vaccine was designed for COVID-19 using envelope protein as an immunogenic target. Nevertheless, the proposed vaccine is rapidly needed to be validated clinically in order to ensure its safety, immunogenic profile and to help on stopping this epidemic before it leads to devastating global outbreaks.

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bioRxiv2019

Identification of Six novel missense single nucleotide polymorphisms in MAOA gene predisposing to aggressive behavior. Bioinformatics study.

BackgroundAn astonishing observation is that aggressive behavior is actually a highly heritable. Recent experimental work and behavior research has linked individual variation in a functional polymorphism of the monoamine oxidase-A gene (MAOA) to the occurrence of anger-driven aggression. Aggressive antisocial and violent behavior has become a regularly debated topic in the scientific community; the impending question is what is the source of aggressive behavior, is it genetic or environmental or is it just an individual choice. This study aims to analyses the SNPs found in MAOA gene and it is possible association to aggressive behavior. MethodVarious bioinformatics software (SIFT, PolyPhen-2, PROVEAN, SNAP22, SNP&GO and PMut)is used to analyses the SNPs within the MAOA gene to study the structural and functional implication on the associated protein, which is further clarified using chimera software. Then gene-gene interaction is studied with geneMANIA software. Furthermore, conservation and annotation studies were done through the ConSurf server and Variant Effect Predictor (VEP) respectively. ResultSix missense SNPs were found to affect the structural and functional prospect of MAOA protein. ConclusionGenetic mutation within MAOA is likely to be associated with aggressive behavior; this will enrich future management and screening possibilities for this behavior.

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bioRxiv2019

Extensive In Silico Analysis of ATL1 Gene: Discovered Five Mutations that may Cause Hereditary Spastic Paraplegia Type 3A

BACKGROUNDHereditary spastic paraplegia type 3A (SPG3A) is a neurodegenerative disease inherited type of Hereditary spastic paraplegia (HSP). It is the second most frequent type of HSP; which Characterized by muscle stiffness with paraplegia and early-onset of symptoms. This is the first translational bioinformatics analysis in a coding region of ATL1 gene which aims to categorize nsSNPs to be used as genomic biomarkers; also it may play a key role in pharmacogenomics by evaluating drug response for this disabling disease.\n\nMETHODSThe raw data of ATL1 gene were retrieved from dbSNP database, and then run into numerous computational analysis tools. Additionally; we submitted the common six deleterious outcomes from the previous functional analysis tools to I-mutant 3.0, and MUPro respectively, to investigate their effect on structural level. The 3D structure of ATL1 was predicted by RaptorX and modeled using UCSF Chimera to compare the differences between the native and the mutant amino acids.\n\nRESULTSFive nsSNPs out of 249 were classified as the most deleterious (rs746927118, rs979765709, rs119476049, rs864622269, rs1242753115).\n\nCONCLUSIONSIn this study the impact of nsSNPs in the ATL1 gene was investigated by various bioinformatics tools, that revealed five nsSNPs (V67F, T120I, R217Q, R495W and G504E) are deleterious SNPs, which have a functional impact on ATL1 protein; and therefore, can be used as genomic biomarkers specifically before 4 years old; also it may play a key role in pharmacogenomics by evaluating drug response for this disabling disease.

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bioRxiv2019

In silico analysis of CDC73 gene revealing 11 novel SNPs associated with Jaw Tumor Syndrome

Back groundhyperparathyroidism-jaw tumor (HPT-JT) is an autosomal dominant disorder with variable expression, with an estimated prevalence of 6.7 per 1,000 population. Genetic testing for predisposing CDC73 (HRPT2) mutations has been an important clinical advance, aimed at early detection and/or treatment to prevent advanced disease. The aim of this study is to assess the effect of SNPs on CDC73 structure and function using different bioinformatics tools.\n\nMethodComputational analysis using eight different in-silico tools including SIFT, PROVEAN, PolyPhen-2, SNAP2, PhD-SNP, SNPs&GO, PMut and Imutant were used to identify the impact on the structure and/or function of CDC73 gene that might be causing jaw tumour.\n\nResultsFrom (733) SNPs identified in the CDC73 gene we found that only Eleven were deleterious to the function and structure of protein and expected to cause syndrome.\n\nConclusionEleven substantial genetic/molecular aberrations in CDC73 gene were identified that could serve as actionable targets for chemotherapeutic intervention in patients whose disease is no longer surgically curable.

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bioRxiv2019

Identification of novel key biomarkers in Simpson-Golabi-Behmel Syndrome: Evidence from bioinformatics analysis

BackgroundThe Simpson-Golabi-Behmel Syndrome (SGBS) or overgrowth Syndrome is a rare inherited X-linked condition characterized by pre- and postnatal overgrowth. The aim of the present study is to identify functional non-synonymous SNPs of GPC3 gene using various in silico approaches. These SNPs are supposed to have a direct effect on protein stability through conformation changes.\n\nMaterial and methodsThe SNPs were retrieved from the Single Nucleotide Polymorphism database (dbSNP) and further used to investigate a damaging effect using SIFT, PolyPhen, PROVEAN, SNAP2, SNPs&GO, PHD-SNP and P-mut, While we used I-mutant and MUPro to study the effect of SNPs on GPC3 protein structure. The 3D structure of human GPC3 protein is not available in the Protein Data Bank, so we used RaptorX to generate a 3D structural model for wild-type GPC3 to visualize the amino acids changes by UCSF Chimera. For biophysical validation we used project HOPE. Lastly we run conservational analysis by BioEdit and Consurf web server respectively.\n\nResultsour results revealed three novel missense mutations (rs1460413167, rs1295603457 and rs757475450) that are found to be the most deleterious which effect on the GPC3 structure and function.\n\nConclusionThis present study could provide a novel insight into the molecular basis of overgrowth Syndrome.

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bioRxiv2019

In Silico Genetics Revealing Novel Mutations in CEBPA Gene Associated with Acute Myeloid Leukemia

BackgroundMyelodysplastic syndrome/Acute myeloid leukemia (MDS/AML) is a highly heterogeneous malignant disease; affects children and adults of all ages. AML is one of the main causes of death in children with cancer. However, It is the most common acute leukemia in adults, with a frequency of over 20 000 cases per year in the United States of America alone.\n\nMethodsThe SNPs were retrieved from the dbSNP database. this SNPs were submitted into various functional analysis tools that done by SIFT, PolyPhen-2, PROVEAN, SNAP2, SNPs&GO, PhD-SNP and PANTHER, while structural analysis were done by I-mutant3 and MUPro. The most damaging SNPs were selected for further analysis by Mutation3D, Project hope, ConSurf and BioEdit softwares.\n\nResultsA total of five novel nsSNPs out of 248 missense mutations were predicted to be responsible for the structural and functional variations of CEBPA protein.\n\nConclusionIn this study the impact of functional SNPs in the CEBPA gene was investigated through different computational methods, which determined that (R339W, R288P, N292S N292T and D63N) are novel SNPs have a potential functional effect and can thus be used as diagnostic markers and may facilitate in genetic studies with a special consideration of the large heterogeneity of AML among the different populations.

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bioRxiv2019

Comprehensive bioinformatics analysis of L1CAM gene revealed Novel Pathological mutations associated with L1 syndrome

BackgroundMutations in the human L1CAM gene cause a group of neurodevelopmental disorders known as L1 syndrome (CRASH syndrome). The L1CAM gene provides instructions for producing the L1 protein, which is found all over the nervous system on the surface of neurons. L1 syndrome involves a variety of characteristics but the most common characteristic is muscle stiffness. Patients with L1 syndrome can also suffer from difficulty speaking, seizures, and underdeveloped or absent tissue connecting the left and right halves of the brain. MethodThe human L1CAM gene was studied from dbSNP/NCBI, 1499 SNPs were Homo sapiens; of which 450 were missense mutations. This selected for Comprehensive bioinformatics analysis by several in silico tools to investigate the effect of SNPs on L1CAM proteins structure and function. Results34 missense mutations (26 novel mutations) out of 450 nsSNPs that are found to be the most deleterious that effect on the L1CAM structural and functional level. ConclusionBetter understanding of L1 syndrome caused by mutations in L1CAM gene was achieved using Comprehensive bioinformatics analysis. These findings describe 35 novel L1 mutations which improve our understanding on genotype-phenotype correlation. And can be used as diagnostic markers for L1 syndrome and besides in cancer diagnosis specifically in breast cancer.

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bioRxiv2019

In silico analysis of IDH3A gene revealed Novel mutations associated with Retinitis Pigmentosa

BackgroundRetinitis Pigmentosa (RP) refers to a group of inherited disorders characterized by the death of photoreceptor cells leading to blindness. The aim of this study is to identify the pathogenic SNPs in the IDH3A gene and their effect on the structure and function of the protein. Methodwe used different bioinformatics tools to predict the effect of each SNP on the structure and function of the protein. Result20 deleterious SNPs out of 178 were found to have a damaging effect on the protein structure and function. Conclusionthis is the first in silico analysis of IDH3A gene and 20 novel mutations were found using different bioinformatics tools, and they could be used as diagnostic markers for Retinitis Pigmentosa.

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bioRxiv2019

In Silico Analysis and Modeling of Novel Pathogenic Single Nucleotide Polymorphisms (SNPs) in Human CD40LG Gene

AbstractO_ST_ABSBackgroundC_ST_ABSThe X-linked hyper-immunoglobulin M syndrome (XHIGM) is a rare, inherited immune deficiency disorder. It is more common in males. Characterized by elevated serum IgM levels and low to undetectable levels of serum IgG, IgA and IgE. Hyper-IgM syndrome is caused by mutations in the CD40LG gene. Located in human Xq26. CD40LG acts as an immune modulator in activated T cells. MethodWe used different bioinformatics tools to predict the effect of each SNP on the structure and function of the protein. Result8 novel SNPs out of 233 were found to have most deleterious effect on the protein structure and function. While modeling of nsSNPs was studied by Project HOPE software. ConclusionBetter understanding of Hyper-IgM syndrome caused by mutations in CD40LG gene was achieved using in silico analysis. This is the first in silico functional analysis of CD40LG gene and 8 novel mutations were found using different bioinformatics tools, and they could be used as diagnostic markers for hyper-IgM syndrome. These 8 novel SNPs may be important candidates for the cause of different types of human diseases by CD40LG gene.

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bioRxiv2019

In Silico Genetics: Identification of pathogenic nsSNPs in human STAT3 gene associated with Job's syndrome

BackgroundAutosomal dominant hyper-IgE syndrome (AD-HIES) or Jobs syndrome is a rare immunodeficiesncy disease that classically presents in early childhood, characterized by eczematoid dermatitis, characteristic facies, pneumatoceles, hyperextensibility of joints, multiple bone fractures, scoliosis, atopic dermatitis and elevated levels of serum IgE (>2000 IU/ml). The term Autosomal dominant hyper-IgE syndrome has primarily been associated with mutations in STAT3 gene, Located in human chromosome 17q21. MethodsThe human STAT3 gene was investigated in dbSNP/NCBI, 962 SNPs were Homo sapiens; of which 255 were missense SNPs. This selected for in silico analysis by multiple in silico tools to investigate the effect of SNPs on STAT3 proteins structure and function. ResultEleven novel mutations out of 255 nsSNPs that are found to be deleterious effect on the STAT3 structure and function. ConclusionA total of eleven novel nsSNPs were predicted to be responsible for the structural and functional modifications of STAT3 protein. The newly recognized genetic cause of the hyper-IgE syndrome affects complex, compartmentalized somatic and immune regulation. This study will opens new doors to facilitate the development of novel diagnostic markers for associated diseases.

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bioRxiv2019

Novel mutations within PRSS1 Gene that could potentially cause hereditary pancreatitis: Using Comprehensive in silico Approach

BackgroundHereditary pancreatitis (HP) is an autosomal dominant disorder with incomplete penetrance characterized by recurring episodes of severe abdominal pain often presenting in childhood. The comprehensive in silico analysis of coding SNPs, and their functional impacts on protein level, still remains unknown. In this study, we aimed to identify the pathogenic SNPs in PRSS1 gene by computational analysis approach.\n\nMaterials and MethodsWe carried out in silico analysis of structural effect of each SNP using different bioinformatics tools to predict Single-nucleotide polymorphisms influence on protein structure and function.\n\nResultTwo novel mutations out of 339 nsSNPs that are found be deleterious effect on the PRSS1 structure and function.\n\nConclusionThis is the first in silico analysis in PRSS1 gene, which will be a valuable resource for future targeted mechanistic and population-based studies.

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