A model for the non-structural 5a (NS5A) protein of Hepatitis-C virus is proposed. It is a hub pr... more A model for the non-structural 5a (NS5A) protein of Hepatitis-C virus is proposed. It is a hub promiscuous multifunctional protein with roles in virus replication and host interactions. The 3D-structure for domainII was predicted based on, the Homo Sapiens Replication factor-A protein-1 (RPA1), as a template using consensus meta-servers results. DomainIII is an intrinsically unstructured domain (61% intrinsically-disorder regions) that lacks a unique 3Dstructure and participates in diverse protein interactions in different situations. It also has a single-stranded DNAbinding protein motif (SSDP) signature for pyrimidine binding during viral replication. Two protein binding motifs with high sequence conservation and disordered regions are proposed; the first corresponds to an Interleukin-8B receptor signature (IL-8R-B), while the second has a lymphotoxin beta receptor (LTβR) high local similarity. A mechanism is proposed to their contribution to NS5A Interferon signaling pathway interception. Lastly, the overlapping between LTβR and SSDP is considered as a sign for NS5A date hubs.
Hepatocellular carcinoma is a devastating tumor which accounts for death mortality rate 94% globa... more Hepatocellular carcinoma is a devastating tumor which accounts for death mortality rate 94% globally, and about 780,000 new cases each year. Tumor suppressor miRNAs represent a class of noncoding RNAs, which exhibit decreased or inhibited expression in the case of carcinogenesis. Therefore, the replacement of these molecules leads to post-transcriptional regulation of tens to hundreds of oncogenic targets and limiting the tumor. Interestingly, there is a group of tumor silencer miRNAs that have been highlighted in HCC and herein, our review will discuss the prominent examples of these miRs in terms of their efficient delivery using vectors, nano-delivery systems, their successful models either in vitro or in vivo and pre-clinical trials. Collectively, tumor suppressor miRNAs can act as novel therapeutics for HCC and more studies should be directed towards these promising therapeutics.
Encyclopedia of Bioinformatics and Computational Biology, 2019
Non-synonymous Single – Nucleotide Variants (nsSNVs) and mutations can create a diversity of the ... more Non-synonymous Single – Nucleotide Variants (nsSNVs) and mutations can create a diversity of the contrary influence of proteins like varying genotype and phenotype of any protein which affects its stability. The alterations in the protein stability may cause diseases. Detecting of nsSNVs and mutations can be a helpful tool in diagnosing diseases at an early stage. The study of singular and consensus tools for predicting pathogenic effects is very essential. Many studies utilized various predicting servers based on distinct Machine Learning Techniques (MLTs). In this research, we conduct a comprehensive study to most of the provided tools or servers that predict disease-causing mutations and the pathogenic effects of nsSNVs with a concentration on the most common. We collected the best unique tools that predict nsSNVs and Meta tools that merge between some of them to enhance the accuracy of the predicting. By comparing the results, we observed that REVEL, CADD, COVEC, Meta-SNP, PAPI, and Condel are better tools than other ensemble tools and PON-P2, SNP dryad, CHASM, PROVEAN, PhD-SNP g , and Mutation Assessor are better tools than other unique tools. The Meta (ensemble) classifiers are better than unique ones as they have the highest overall performance.
MicroRNAs are well known as short RNAs bases, 22 nucleotides, binding directly to 3'untransla... more MicroRNAs are well known as short RNAs bases, 22 nucleotides, binding directly to 3'untranslated region (3'UTR) of the messenger RNA to repress their functions. Recently, microRNAs have been widely used as a therapeutic approach for various types of Cancer. MicroRNA is categorized into tumor suppressor and oncomirs. Tumor suppressor microRNAs can repress the pathologically causative oncogenes of the hallmarks of Cancer. However, based on the fact that miRNA has no proper fidelity to bind specific mRNAs due to binding to off-targets, it results in a kind of inverse biological activity. Here, we have executed an in-silico integrative analysis of GEO/TCGA-LIHC of genes/microRNAs expression analysis in HCC, including (446 HCC vs. 146 normal specimens for miRNAs expression ) ad 488 specimens for genes expression. It virtually shows that microRNAs could have an ability to target both oncogenes and tumor suppressor genes that contribute to its dual activity role as a tumor suppress...
3 Abstract: Influenza A viruses infects birds, animals and humans and it has the ability to mutat... more 3 Abstract: Influenza A viruses infects birds, animals and humans and it has the ability to mutate and develop mutant variants which may cause unexpected events. There is an urgent need for new medications to combat influenza pandemics. Using the genome sequences of the influenza A virus performed previously, we designed and performed a combinatorial exhaustive systematic methodology for optimal design of universal therapeutic short-interfering RNA (siRNA) molecules targeting all diverse of the virus strains. By using the bioinformatics tools, we designed siRNA targeting influenza A virus polymerase genes. The selection and validation of optimal siRNAs was also studied. The influenza A virus subtype H1N1 and H5N1 were propagated in MDCK cells. TCID and HA assays were performed and real time PCR for assessment of viral load was used. Time- 50 dependent and dosage-dependent usage were performed and showed high decrease in viral load.
The International Journal of Biochemistry & Cell Biology, 2021
BACKGROUND Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder associated with severa... more BACKGROUND Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder associated with several complications. Adipose-tissue-derived mesenchymal stem cells (AT-MSCs) possess high plasticity and differentiation capabilities and are useful for treating inflammation-related disorders such as T2DM. However, the pathogenic microenvironment of T2DM may affect their therapeutic potential. We aimed to examine the impact of the diabetic milieu on the immunomodulatory/anti-inflammatory potential of AT-MSCs. METHODS We assessed the proliferation potential, cell surface expression of MSC-characteristic markers and immunomodulatory markers, along with the gene expression and secretion of pro-inflammatory and anti-inflammatory cytokines and adipokines in AT-MSCs derived from T2DM patients (dAT-MSCs) vs. non-diabetic volunteers (ndAT-MSCs). Furthermore, we evaluated the IFN-γ priming effect on both groups. RESULTS Our data revealed comparable proliferative activities in both groups. Elevated IL-1β mRNA expression associated with a downregulation of IL-1RN was observed in dAT-MSCs vs. ndAT-MSCs. Flow cytometric analysis results showed a lower expression of CD200 and CD276 on dAT-MSCs relative to ndAT-MSCs. IFN-γ priming induced an elevation in CD274 expression associated with IDO1 and ILRN overexpression and IL-1β downregulation in both groups. Enzyme-linked immunosorbent assay (ELISA) uncovered elevated levels of secreted IL-1β, TNF, and visfatin/NAMPT in dAT-MSCs, whereas IL-1RA and IDO levels were reduced. ELISA results were also evident in the secretome of dAT-MSCs upon IFN-γ priming. CONCLUSIONS This study suggests that the T2DM milieu alters the immunomodulatory characteristics of AT-MSCs with a shift towards a proinflammatory phenotype which may restrain their autologous therapeutic use. Furthermore, IFN-γ priming could be a useful strategy for enhancing their anti-inflammatory potential.
Biomarker determination is a very important issue in medical research. Knowing the biomarker, bet... more Biomarker determination is a very important issue in medical research. Knowing the biomarker, better prognosis and diagnosis could be reached. Experimental prediction of biomarkers is lengthy and very costly. Recently, many studies have been conducted in the area of bioinformatics for In-silico prediction of biomarkers. This is assumed to save a lot of money while enabling us to explore many genetic issues. In this paper we provide a method to extract the most likely genes that could be considered as informative genes in microarrays of Hepatocellular Carcinoma. The used dataset is composed of fifty samples (19 normal and 31 abnormal samples). We extract the informative genes as those having the highest entropy. Those genes are considered as candidate biomarkers. The genes that have the highest mutual information with the well-known tumor biomarker Alpha fetoprotein gene are considered as candidate biomarkers. The results are validated by examining the presence of the experimentally ...
Interferon plus Ribavirin is the standard treatment for chronic hepatitis C is often accompanied ... more Interferon plus Ribavirin is the standard treatment for chronic hepatitis C is often accompanied by adverse side effects and unfortunately fails in almost half of cases. The ability to predict such failures previous to treatment could save a great deal of pain and expense for the patient with HCV. Decision tree with CART classification algorithm was developed to forecast response to therapy with 200 chronic hepatitis C patients. The data was divided where 150 cases were used to create the classifier and 50 cases for validation. HAI (hepatitis activity index), Fibrosis, ALT, age, and Gender were used as predictors for response of therapy. The overall classification error was 20% and 80% was the best accuracy, sensitivity and specificity were 0.80, 0.89% and 78%, respectively were results from validation stage as the following, true cases are 40 from 50 (total number of validation cases) and false cases 10 (represent error 20%). This model will help the physicians to build a decision ...
Representational biases that are common in biological data can inflate prediction performance and... more Representational biases that are common in biological data can inflate prediction performance and confound our understanding of how and what machine learning (ML) models learn from large complicated datasets. However, auditing for these biases is not a common practice in ML in the life sciences. Here, we devise a systematic auditing framework and harness it to audit three different ML applications of significant therapeutic interest: prediction frameworks of protein-protein interactions, drug-target bioactivity, and MHC-peptide binding. Through this, we identify unrecognized biases that hinder the ML process and result in low model generalizability. Ultimately, we show that, when there is insufficient signal in the training data, ML models are likely to learn primarily from representational biases.
OBJECTIVES Chronic hepatitis C virus (HCV) infection is a debilitating disease that is lately tre... more OBJECTIVES Chronic hepatitis C virus (HCV) infection is a debilitating disease that is lately treated using direct-acting antivirals (DAAs). Changes in the oral microbiome were detected in other liver diseases; however, oral microbiome was never investigated in patients having chronic HCV infection, whether pre- or post-treatment. MATERIALS AND METHODS This case-control preliminary study enrolled three equal groups. Group (I) included untreated HCV patients; group (II): HCV patients who achieved viral clearance after DAA administration; and group (III): healthy controls. For each participant, a buccal swab was harvested and its 16S rRNA was sequenced. RESULTS The oral microbiome of chronic HCV patients had a significantly distinct bacterial community compared to healthy controls, characterized by high diversity and abundance of certain pathogenic species. These changes resemble that of oral lichen planus patients. After treatment by DAAs, the oral microbiome shifted to a community with partial similarity to both the diseased and healthy ones. CONCLUSIONS Chronic HCV is associated with dysbiotic oral microbiome having abundant pathogenic bacteria. With HCV clearance by DAAs, the oral microbiome shifts to approach the healthy composition.
Background MicroRNAs are emerging as new mediators in the regulation of adipocyte physiology and ... more Background MicroRNAs are emerging as new mediators in the regulation of adipocyte physiology and have been approved to play a role in obesity. Despite several studies have focused on microRNA expression profiles and functions in different metabolic tissues, little is known about their response to nutritional interventions in white adipose tissue during obesity stages, and whether they differ in this response to weight-reduction strategy is poorly understood. Our objectives were to study the dysregulation of some miRNAs in subcutaneous inguinal white adipose tissue during weight change, expansion/reduction; in response to both a high-fat diet and switching to a normal diet feeding, and to evaluate them as potential biomarkers and therapeutic targets for early obesity management Method A hundred 6-week-old male Wister rats were randomly divided into a normal diet group (N.D), a high-fat diet group (H.F.D), and a switched to a normal diet group (H.F.D/N.D). At the beginning and at inte...
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, the causative agent of coronavirus d... more Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, the causative agent of coronavirus disease (COVID-19)) has caused relatively high mortality rates in humans throughout the world since its first detection in late December 2019, leading to the most devastating pandemic of the current century. Consequently, SARS-CoV-2 therapeutic interventions have received high priority from public health authorities. Despite increased COVID-19 infections, a vaccine or therapy to cover all the population is not yet available. Herein, immunoinformatics and custommune tools were used to identify B and T-cells epitopes from the available SARS-CoV-2 sequences spike (S) protein. In the in silico predictions, six B cell epitopes QTGKIADYNYK, TEIYQASTPCNGVEG, LQSYGFQPT, IRGDEVRQIAPGQTGKIADYNYKLPD, FSQILPDPSKPSKRS and PFAMQMAYRFNG were cross-reacted with MHC-I and MHC-II T-cells binding epitopes and selected for vaccination in experimental animals for evaluation as candidate vaccine(s) due to thei...
Egyptians are at a crossroad between Africa and Eurasia, providing useful genomic resources for a... more Egyptians are at a crossroad between Africa and Eurasia, providing useful genomic resources for analyzing both genetic and environmental factors for future personalized medicine. Two personal Egyptian whole genomes have been published previously by us and here nine female whole genome sequences with clinical information have been added to expand the genomic resource of Egyptian personal genomes. Here we report the analysis of whole genomes of nine Egyptian females from different regions using Illumina short-read sequencers. At 30x sequencing coverage, we identified 12 SNPs that were shared in most of the subjects associated with obesity which are concordant with their clinical diagnosis. Also, we found mtDNA mutation A4282G is common in all the samples and this is associated with chronic progressive external ophthalmoplegia (CPEO). Haplogroup and Admixture analyses revealed that most Egyptian samples are close to the other north Mediterranean, Middle Eastern, and European, respectively, possibly reflecting the into-Africa influx of human migration. In conclusion, we present whole-genome sequences of nine Egyptian females with personal clinical information that cover the diverse regions of Egypt. Although limited in sample size, the whole genomes data provides possible geno-phenotype candidate markers that are relevant to the region's diseases.
Computational prediction of immunogenic epitopes is a promising platform for therapeutic and prev... more Computational prediction of immunogenic epitopes is a promising platform for therapeutic and preventive vaccine design. A potential target for this strategy is human immunodeficiency virus (HIV-1), for which, despite decades of efforts, no vaccine is available. In particular, a therapeutic vaccine devised to eliminate infected cells would represent a key component of cure strategies. HIV peptides designed based on individual viro-immunological data from people living with HIV/AIDS have recently shown able to induce post-therapy viral set point abatement. However, the reproducibility and scalability of this method is curtailed by the errors and arbitrariness associated with manual peptide design as well as by the time-consuming process.We herein introduce Custommune, a user-friendly web tool to design personalized and population-targeted vaccines. When applied to HIV-1, Custommune predicted personalized epitopes using patient specific Human Leukocyte Antigen (HLA) alleles and viral s...
Diabetes research and clinical practice, Jan 4, 2018
The increased incidence of type 2 diabetes mellitus (T2DM) and the importance of early identifica... more The increased incidence of type 2 diabetes mellitus (T2DM) and the importance of early identification and management of its complications, especially diabetic nephropathy (DN), have spotted the light on genetic factors that increase risk of T2DM and its related nephropathy. The present study aimed at investigating expression of (KCNJ11, ABCC8, JAZF1, WFS1, PPARG, NOTCH2 and EXOSC4) genes in peripheral blood of T2DM patients. The study included 30 non-complicated T2DM patients, 30 patients with DN and 40 healthy controls. Quantitative Real Time PCR Array was used to study gene expression. NOTCH2 showed higher expression while KCNJ11, JAZF1, WFS1 and PPARG genes showed lower expression in DN patients compared to non-complicated patients. KCNJ11, JAZF1, WFS1, PPARG, and EXOSC4 expression showed significant negative correlation with microalbumin, while NOTCH2 expression was significantly positively correlated with microalbumin. AS regard HbA1c and studied genes expression, there was sig...
The p7-transactivated protein of Hepatitis C virus is a small integral membrane protein of 127 am... more The p7-transactivated protein of Hepatitis C virus is a small integral membrane protein of 127 amino acids, which is crucial for assembly and release of infectious virions. Ab initio and comparative modelling, is an essential tool to solve the problem of protein structure prediction and to comprehend the physicochemical fundemental of how proteins fold in nature. Only one domain (1-127) of p7 had been predicted using the systematic in silico approach, ThreaDom. I-TASSER was ranked as the best server for full-length 3-D protein structural predictions of p7 where the benchmarked scoring system such as C-score, TM-score, RMSD and Z-score are used to obtain quantitative assessments of the I-TASSER models. Scanning protein motif databases, along with secondary and surface accessibility predictions integrated with post translational modification sites (PTMs) prediction revealed functional and protein binding motifs. Three protein binding motifs (two Asp/Glutamnse, CTNNB1-bd_N) with high s...
A model for the non-structural 5a (NS5A) protein of Hepatitis-C virus is proposed. It is a hub pr... more A model for the non-structural 5a (NS5A) protein of Hepatitis-C virus is proposed. It is a hub promiscuous multifunctional protein with roles in virus replication and host interactions. The 3D-structure for domainII was predicted based on, the Homo Sapiens Replication factor-A protein-1 (RPA1), as a template using consensus meta-servers results. DomainIII is an intrinsically unstructured domain (61% intrinsically-disorder regions) that lacks a unique 3Dstructure and participates in diverse protein interactions in different situations. It also has a single-stranded DNAbinding protein motif (SSDP) signature for pyrimidine binding during viral replication. Two protein binding motifs with high sequence conservation and disordered regions are proposed; the first corresponds to an Interleukin-8B receptor signature (IL-8R-B), while the second has a lymphotoxin beta receptor (LTβR) high local similarity. A mechanism is proposed to their contribution to NS5A Interferon signaling pathway interception. Lastly, the overlapping between LTβR and SSDP is considered as a sign for NS5A date hubs.
Hepatocellular carcinoma is a devastating tumor which accounts for death mortality rate 94% globa... more Hepatocellular carcinoma is a devastating tumor which accounts for death mortality rate 94% globally, and about 780,000 new cases each year. Tumor suppressor miRNAs represent a class of noncoding RNAs, which exhibit decreased or inhibited expression in the case of carcinogenesis. Therefore, the replacement of these molecules leads to post-transcriptional regulation of tens to hundreds of oncogenic targets and limiting the tumor. Interestingly, there is a group of tumor silencer miRNAs that have been highlighted in HCC and herein, our review will discuss the prominent examples of these miRs in terms of their efficient delivery using vectors, nano-delivery systems, their successful models either in vitro or in vivo and pre-clinical trials. Collectively, tumor suppressor miRNAs can act as novel therapeutics for HCC and more studies should be directed towards these promising therapeutics.
Encyclopedia of Bioinformatics and Computational Biology, 2019
Non-synonymous Single – Nucleotide Variants (nsSNVs) and mutations can create a diversity of the ... more Non-synonymous Single – Nucleotide Variants (nsSNVs) and mutations can create a diversity of the contrary influence of proteins like varying genotype and phenotype of any protein which affects its stability. The alterations in the protein stability may cause diseases. Detecting of nsSNVs and mutations can be a helpful tool in diagnosing diseases at an early stage. The study of singular and consensus tools for predicting pathogenic effects is very essential. Many studies utilized various predicting servers based on distinct Machine Learning Techniques (MLTs). In this research, we conduct a comprehensive study to most of the provided tools or servers that predict disease-causing mutations and the pathogenic effects of nsSNVs with a concentration on the most common. We collected the best unique tools that predict nsSNVs and Meta tools that merge between some of them to enhance the accuracy of the predicting. By comparing the results, we observed that REVEL, CADD, COVEC, Meta-SNP, PAPI, and Condel are better tools than other ensemble tools and PON-P2, SNP dryad, CHASM, PROVEAN, PhD-SNP g , and Mutation Assessor are better tools than other unique tools. The Meta (ensemble) classifiers are better than unique ones as they have the highest overall performance.
MicroRNAs are well known as short RNAs bases, 22 nucleotides, binding directly to 3'untransla... more MicroRNAs are well known as short RNAs bases, 22 nucleotides, binding directly to 3'untranslated region (3'UTR) of the messenger RNA to repress their functions. Recently, microRNAs have been widely used as a therapeutic approach for various types of Cancer. MicroRNA is categorized into tumor suppressor and oncomirs. Tumor suppressor microRNAs can repress the pathologically causative oncogenes of the hallmarks of Cancer. However, based on the fact that miRNA has no proper fidelity to bind specific mRNAs due to binding to off-targets, it results in a kind of inverse biological activity. Here, we have executed an in-silico integrative analysis of GEO/TCGA-LIHC of genes/microRNAs expression analysis in HCC, including (446 HCC vs. 146 normal specimens for miRNAs expression ) ad 488 specimens for genes expression. It virtually shows that microRNAs could have an ability to target both oncogenes and tumor suppressor genes that contribute to its dual activity role as a tumor suppress...
3 Abstract: Influenza A viruses infects birds, animals and humans and it has the ability to mutat... more 3 Abstract: Influenza A viruses infects birds, animals and humans and it has the ability to mutate and develop mutant variants which may cause unexpected events. There is an urgent need for new medications to combat influenza pandemics. Using the genome sequences of the influenza A virus performed previously, we designed and performed a combinatorial exhaustive systematic methodology for optimal design of universal therapeutic short-interfering RNA (siRNA) molecules targeting all diverse of the virus strains. By using the bioinformatics tools, we designed siRNA targeting influenza A virus polymerase genes. The selection and validation of optimal siRNAs was also studied. The influenza A virus subtype H1N1 and H5N1 were propagated in MDCK cells. TCID and HA assays were performed and real time PCR for assessment of viral load was used. Time- 50 dependent and dosage-dependent usage were performed and showed high decrease in viral load.
The International Journal of Biochemistry & Cell Biology, 2021
BACKGROUND Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder associated with severa... more BACKGROUND Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder associated with several complications. Adipose-tissue-derived mesenchymal stem cells (AT-MSCs) possess high plasticity and differentiation capabilities and are useful for treating inflammation-related disorders such as T2DM. However, the pathogenic microenvironment of T2DM may affect their therapeutic potential. We aimed to examine the impact of the diabetic milieu on the immunomodulatory/anti-inflammatory potential of AT-MSCs. METHODS We assessed the proliferation potential, cell surface expression of MSC-characteristic markers and immunomodulatory markers, along with the gene expression and secretion of pro-inflammatory and anti-inflammatory cytokines and adipokines in AT-MSCs derived from T2DM patients (dAT-MSCs) vs. non-diabetic volunteers (ndAT-MSCs). Furthermore, we evaluated the IFN-γ priming effect on both groups. RESULTS Our data revealed comparable proliferative activities in both groups. Elevated IL-1β mRNA expression associated with a downregulation of IL-1RN was observed in dAT-MSCs vs. ndAT-MSCs. Flow cytometric analysis results showed a lower expression of CD200 and CD276 on dAT-MSCs relative to ndAT-MSCs. IFN-γ priming induced an elevation in CD274 expression associated with IDO1 and ILRN overexpression and IL-1β downregulation in both groups. Enzyme-linked immunosorbent assay (ELISA) uncovered elevated levels of secreted IL-1β, TNF, and visfatin/NAMPT in dAT-MSCs, whereas IL-1RA and IDO levels were reduced. ELISA results were also evident in the secretome of dAT-MSCs upon IFN-γ priming. CONCLUSIONS This study suggests that the T2DM milieu alters the immunomodulatory characteristics of AT-MSCs with a shift towards a proinflammatory phenotype which may restrain their autologous therapeutic use. Furthermore, IFN-γ priming could be a useful strategy for enhancing their anti-inflammatory potential.
Biomarker determination is a very important issue in medical research. Knowing the biomarker, bet... more Biomarker determination is a very important issue in medical research. Knowing the biomarker, better prognosis and diagnosis could be reached. Experimental prediction of biomarkers is lengthy and very costly. Recently, many studies have been conducted in the area of bioinformatics for In-silico prediction of biomarkers. This is assumed to save a lot of money while enabling us to explore many genetic issues. In this paper we provide a method to extract the most likely genes that could be considered as informative genes in microarrays of Hepatocellular Carcinoma. The used dataset is composed of fifty samples (19 normal and 31 abnormal samples). We extract the informative genes as those having the highest entropy. Those genes are considered as candidate biomarkers. The genes that have the highest mutual information with the well-known tumor biomarker Alpha fetoprotein gene are considered as candidate biomarkers. The results are validated by examining the presence of the experimentally ...
Interferon plus Ribavirin is the standard treatment for chronic hepatitis C is often accompanied ... more Interferon plus Ribavirin is the standard treatment for chronic hepatitis C is often accompanied by adverse side effects and unfortunately fails in almost half of cases. The ability to predict such failures previous to treatment could save a great deal of pain and expense for the patient with HCV. Decision tree with CART classification algorithm was developed to forecast response to therapy with 200 chronic hepatitis C patients. The data was divided where 150 cases were used to create the classifier and 50 cases for validation. HAI (hepatitis activity index), Fibrosis, ALT, age, and Gender were used as predictors for response of therapy. The overall classification error was 20% and 80% was the best accuracy, sensitivity and specificity were 0.80, 0.89% and 78%, respectively were results from validation stage as the following, true cases are 40 from 50 (total number of validation cases) and false cases 10 (represent error 20%). This model will help the physicians to build a decision ...
Representational biases that are common in biological data can inflate prediction performance and... more Representational biases that are common in biological data can inflate prediction performance and confound our understanding of how and what machine learning (ML) models learn from large complicated datasets. However, auditing for these biases is not a common practice in ML in the life sciences. Here, we devise a systematic auditing framework and harness it to audit three different ML applications of significant therapeutic interest: prediction frameworks of protein-protein interactions, drug-target bioactivity, and MHC-peptide binding. Through this, we identify unrecognized biases that hinder the ML process and result in low model generalizability. Ultimately, we show that, when there is insufficient signal in the training data, ML models are likely to learn primarily from representational biases.
OBJECTIVES Chronic hepatitis C virus (HCV) infection is a debilitating disease that is lately tre... more OBJECTIVES Chronic hepatitis C virus (HCV) infection is a debilitating disease that is lately treated using direct-acting antivirals (DAAs). Changes in the oral microbiome were detected in other liver diseases; however, oral microbiome was never investigated in patients having chronic HCV infection, whether pre- or post-treatment. MATERIALS AND METHODS This case-control preliminary study enrolled three equal groups. Group (I) included untreated HCV patients; group (II): HCV patients who achieved viral clearance after DAA administration; and group (III): healthy controls. For each participant, a buccal swab was harvested and its 16S rRNA was sequenced. RESULTS The oral microbiome of chronic HCV patients had a significantly distinct bacterial community compared to healthy controls, characterized by high diversity and abundance of certain pathogenic species. These changes resemble that of oral lichen planus patients. After treatment by DAAs, the oral microbiome shifted to a community with partial similarity to both the diseased and healthy ones. CONCLUSIONS Chronic HCV is associated with dysbiotic oral microbiome having abundant pathogenic bacteria. With HCV clearance by DAAs, the oral microbiome shifts to approach the healthy composition.
Background MicroRNAs are emerging as new mediators in the regulation of adipocyte physiology and ... more Background MicroRNAs are emerging as new mediators in the regulation of adipocyte physiology and have been approved to play a role in obesity. Despite several studies have focused on microRNA expression profiles and functions in different metabolic tissues, little is known about their response to nutritional interventions in white adipose tissue during obesity stages, and whether they differ in this response to weight-reduction strategy is poorly understood. Our objectives were to study the dysregulation of some miRNAs in subcutaneous inguinal white adipose tissue during weight change, expansion/reduction; in response to both a high-fat diet and switching to a normal diet feeding, and to evaluate them as potential biomarkers and therapeutic targets for early obesity management Method A hundred 6-week-old male Wister rats were randomly divided into a normal diet group (N.D), a high-fat diet group (H.F.D), and a switched to a normal diet group (H.F.D/N.D). At the beginning and at inte...
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, the causative agent of coronavirus d... more Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, the causative agent of coronavirus disease (COVID-19)) has caused relatively high mortality rates in humans throughout the world since its first detection in late December 2019, leading to the most devastating pandemic of the current century. Consequently, SARS-CoV-2 therapeutic interventions have received high priority from public health authorities. Despite increased COVID-19 infections, a vaccine or therapy to cover all the population is not yet available. Herein, immunoinformatics and custommune tools were used to identify B and T-cells epitopes from the available SARS-CoV-2 sequences spike (S) protein. In the in silico predictions, six B cell epitopes QTGKIADYNYK, TEIYQASTPCNGVEG, LQSYGFQPT, IRGDEVRQIAPGQTGKIADYNYKLPD, FSQILPDPSKPSKRS and PFAMQMAYRFNG were cross-reacted with MHC-I and MHC-II T-cells binding epitopes and selected for vaccination in experimental animals for evaluation as candidate vaccine(s) due to thei...
Egyptians are at a crossroad between Africa and Eurasia, providing useful genomic resources for a... more Egyptians are at a crossroad between Africa and Eurasia, providing useful genomic resources for analyzing both genetic and environmental factors for future personalized medicine. Two personal Egyptian whole genomes have been published previously by us and here nine female whole genome sequences with clinical information have been added to expand the genomic resource of Egyptian personal genomes. Here we report the analysis of whole genomes of nine Egyptian females from different regions using Illumina short-read sequencers. At 30x sequencing coverage, we identified 12 SNPs that were shared in most of the subjects associated with obesity which are concordant with their clinical diagnosis. Also, we found mtDNA mutation A4282G is common in all the samples and this is associated with chronic progressive external ophthalmoplegia (CPEO). Haplogroup and Admixture analyses revealed that most Egyptian samples are close to the other north Mediterranean, Middle Eastern, and European, respectively, possibly reflecting the into-Africa influx of human migration. In conclusion, we present whole-genome sequences of nine Egyptian females with personal clinical information that cover the diverse regions of Egypt. Although limited in sample size, the whole genomes data provides possible geno-phenotype candidate markers that are relevant to the region's diseases.
Computational prediction of immunogenic epitopes is a promising platform for therapeutic and prev... more Computational prediction of immunogenic epitopes is a promising platform for therapeutic and preventive vaccine design. A potential target for this strategy is human immunodeficiency virus (HIV-1), for which, despite decades of efforts, no vaccine is available. In particular, a therapeutic vaccine devised to eliminate infected cells would represent a key component of cure strategies. HIV peptides designed based on individual viro-immunological data from people living with HIV/AIDS have recently shown able to induce post-therapy viral set point abatement. However, the reproducibility and scalability of this method is curtailed by the errors and arbitrariness associated with manual peptide design as well as by the time-consuming process.We herein introduce Custommune, a user-friendly web tool to design personalized and population-targeted vaccines. When applied to HIV-1, Custommune predicted personalized epitopes using patient specific Human Leukocyte Antigen (HLA) alleles and viral s...
Diabetes research and clinical practice, Jan 4, 2018
The increased incidence of type 2 diabetes mellitus (T2DM) and the importance of early identifica... more The increased incidence of type 2 diabetes mellitus (T2DM) and the importance of early identification and management of its complications, especially diabetic nephropathy (DN), have spotted the light on genetic factors that increase risk of T2DM and its related nephropathy. The present study aimed at investigating expression of (KCNJ11, ABCC8, JAZF1, WFS1, PPARG, NOTCH2 and EXOSC4) genes in peripheral blood of T2DM patients. The study included 30 non-complicated T2DM patients, 30 patients with DN and 40 healthy controls. Quantitative Real Time PCR Array was used to study gene expression. NOTCH2 showed higher expression while KCNJ11, JAZF1, WFS1 and PPARG genes showed lower expression in DN patients compared to non-complicated patients. KCNJ11, JAZF1, WFS1, PPARG, and EXOSC4 expression showed significant negative correlation with microalbumin, while NOTCH2 expression was significantly positively correlated with microalbumin. AS regard HbA1c and studied genes expression, there was sig...
The p7-transactivated protein of Hepatitis C virus is a small integral membrane protein of 127 am... more The p7-transactivated protein of Hepatitis C virus is a small integral membrane protein of 127 amino acids, which is crucial for assembly and release of infectious virions. Ab initio and comparative modelling, is an essential tool to solve the problem of protein structure prediction and to comprehend the physicochemical fundemental of how proteins fold in nature. Only one domain (1-127) of p7 had been predicted using the systematic in silico approach, ThreaDom. I-TASSER was ranked as the best server for full-length 3-D protein structural predictions of p7 where the benchmarked scoring system such as C-score, TM-score, RMSD and Z-score are used to obtain quantitative assessments of the I-TASSER models. Scanning protein motif databases, along with secondary and surface accessibility predictions integrated with post translational modification sites (PTMs) prediction revealed functional and protein binding motifs. Three protein binding motifs (two Asp/Glutamnse, CTNNB1-bd_N) with high s...
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Papers by M. Elhefnawi