Epigenetic Features in Newborns Associated with Preadolescence Lung Function and Asthma Acquisition during Adolescence.

The association between newborn DNA methylation (DNAm) and asthma acquisition (AA) during adolescence has been suggested. Lung function (LF) has been shown to be associated with asthma risk and its severity. However, the role of LF in the associations between DNAm and AA is unclear, and it is also unknown whether the association between DNAm and AA is consistent with that between DNAm and LF. We address this question through assessing newborn epigenetic features of preadolescence LF and of AA during adolescence, along with their biological pathways and processes. Our study's primary medical significance lies in advancing the understanding of asthma's early life origins. By investigating epigenetic markers in newborns and their association with lung function in preadolescence, we aim to uncover potential early biomarkers of asthma risk. This could facilitate earlier detection and intervention strategies. Additionally, exploring biological pathways linking early lung function to later asthma development can offer insights into the disease's pathogenesis, potentially leading to novel therapeutic targets. METHODS: The study was based on the Isle of Wight Birth cohort (IOWBC). Female subjects with DNAm data at birth and with no asthma at age 10 years were included (n = 249). The R package ttScreening was applied to identify CpGs potentially associated with AA from 10 to 18 years and with LF at age 10 (FEV1, FVC, and FEV1/FVC), respectively. Agreement in identified CpGs between AA and LF was examined, along with their biological pathways and processes via the R function gometh. We tested the findings in an independent cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC), to examine overall replicability. RESULTS: In IOWBC, 292 CpGs were detected with DNAm associated with AA and 1517 unique CpGs for LF (514 for FEV1, 436 for FVC, 408 for FEV1/FVC), with one overlapping CpG, cg23642632 (NCKAP1) between AA and LF. Among the IOWBC-identified CpGs, we further tested in ALSPAC and observed the highest agreement between the two cohorts in FVC with respect to the direction of association and statistical significance. Epigenetic enrichment analyses indicated non-specific connections in the biological pathways and processes between AA and LF. CONCLUSIONS: The present study suggests that FEV1, FVC, and FEV1/FVC (as objective measures of LF) and AA (incidence of asthma) are likely to have their own specific epigenetic features and biological pathways at birth. More replications are desirable to fully understand the complexity between DNAm, lung function, and asthma acquisition.

Extended dipeptide composition framework for accurate identification of anticancer peptides.

The identification of anticancer peptides (ACPs) is crucial, especially in the development of peptide-based cancer therapy. The classical models such as Split Amino Acid Composition (SAAC) and Pseudo Amino Acid Composition (PseAAC) lack the incorporation of feature representation. These advancements improve the predictive accuracy and efficiency of ACP identification. Thus, the effort of this research is to propose and develop an advanced framework based on feature extraction. Thus, to achieve this objective herein we propose an Extended Dipeptide Composition (EDPC) framework. The proposed EDPC framework extends the dipeptide composition by considering the local sequence environment information and reforming the CD-HIT framework to remove noise and redundancy. To measure the accuracy, we have performed several experiments. These experiments were employed using four famous machine learning (ML) algorithms named; Support Vector Machine (SVM), Decision Tree (DT), Random Forest (RF), and K Nearest Neighbor (KNN). For comparisons, we have used accuracy, specificity, sensitivity, precision, recall, and F1-Score as evaluation criteria. The reliability of the proposed framework is further evaluated using statistical significance tests. As a result, the proposed EDPC framework exhibited enhanced performance than SAAC and PseAAC, where the SVM model delivered the highest accuracy of 96. 6% and significant enhancements in specificity, sensitivity, precision, and F1-score over multiple datasets. Due to the incorporation of enhanced feature representation and the incorporation of local and global sequence profiles proposed EDPC achieves higher classification performance. The proposed frameworks can deal with noise and also duplicating features. These are accompanied by a wide range of feature representations. Finally, our proposed framework can be used for clinical applications where ACP identification is essential. Future works will include extending to a larger variety of datasets, incorporating tertiary structural information, and using deep learning techniques to improve the proposed EDPC.

An effective deep learning-based approach for splice site identification in gene expression.

A crucial stage in eukaryote gene expression involves mRNA splicing by a protein assembly known as the spliceosome. This step significantly contributes to generating and properly operating the ultimate gene product. Since non-coding introns disrupt eukaryotic genes, splicing entails the elimination of introns and joining exons to create a functional mRNA molecule. Nevertheless, accurately finding splice sequence sites using various molecular biology techniques and other biological approaches is complex and time-consuming. This paper presents a precise and reliable computer-aided diagnosis (CAD) technique for the rapid and correct identification of splice site sequences. The proposed deep learning-based framework uses long short-term memory (LSTM) to extract distinct patterns from RNA sequences, enabling rapid and accurate point mutation sequence mapping. The proposed network employs one-hot encodings to find sequential patterns that effectively identify splicing sites. A thorough ablation study of traditional machine learning, one-dimensional convolutional neural networks (1D-CNNs), and recurrent neural networks (RNNs) models was conducted. The proposed LSTM network outperformed existing state-of-the-art approaches, improving accuracy by 3% and 2% for the acceptor and donor sites datasets.

DeepSplice: a deep learning approach for accurate prediction of alternative splicing events in the human genome.

Alternative splicing (AS) is a crucial process in genetic information processing that generates multiple mRNA molecules from a single gene, producing diverse proteins. Accurate prediction of AS events is essential for understanding various physiological aspects, including disease progression and prognosis. Machine learning (ML) techniques have been widely employed in bioinformatics to address this challenge. However, existing models have limitations in capturing AS events in the presence of mutations and achieving high prediction performance. To overcome these limitations, this research presents deep splicing code (DSC), a deep learning (DL)-based model for AS prediction. The proposed model aims to improve predictive ability by investigating state-of-the-art techniques in AS and developing a DL model specifically designed to predict AS events accurately. The performance of the DSC model is evaluated against existing techniques, revealing its potential to enhance the understanding and predictive power of DL algorithms in AS. It outperforms other models by achieving an average AUC score of 92%. The significance of this research lies in its contribution to identifying functional implications and potential therapeutic targets associated with AS, with applications in genomics, bioinformatics, and biomedical research. The findings of this study have the potential to advance the field and pave the way for more precise and reliable predictions of AS events, ultimately leading to a deeper understanding of genetic information processing and its impact on human physiology and disease.

Molecular screening of phytocompounds targeting the interface between influenza A NS1 and TRIM25 to enhance host immune responses.

BACKGROUND: Influenza A virus causes severe respiratory illnesses, especially in developing nations where most child deaths under 5 occur due to lower respiratory tract infections. The RIG-I protein acts as a sensor for viral dsRNA, triggering interferon production through K63-linked poly-ubiquitin chains synthesized by TRIM25. However, the influenza A virus's NS1 protein hinders this process by binding to TRIM25, disrupting its association with RIG-I and preventing downstream interferon signalling, contributing to the virus's evasion of the immune response. METHODS: In our study we used structural-based drug designing, molecular simulation, and binding free energy approaches to identify the potent phytocompounds from various natural product databases (>100,000 compounds) able to inhibit the binding of NS1 with the TRIM25. RESULTS: The molecular screening identified EA-8411902 and EA-19951545 from East African Natural Products Database, NA-390261 and NA-71 from North African Natural Products Database, SA-65230 and SA- 4477104 from South African Natural Compounds Database, NEA- 361 and NEA- 4524784 from North-East African Natural Products Database, TCM-4444713 and TCM-6056 from Traditional Chinese Medicines Database as top hits. The molecular docking and binding free energies results revealed that these compounds have high affinity with the specific active site residues (Leu95, Ser99, and Tyr89) involved in the interaction with TRIM25. Additionally, analysis of structural dynamics, binding free energy, and dissociation constants demonstrates a notably stronger binding affinity of these compounds with the NS1 protein. Moreover, all selected compounds exhibit exceptional ADMET properties, including high water solubility, gastrointestinal absorption, and an absence of hepatotoxicity, while adhering to Lipinski's rule. CONCLUSION: Our molecular simulation findings highlight that the identified compounds demonstrate high affinity for specific active site residues involved in the NS1-TRIM25 interaction, exhibit exceptional ADMET properties, and adhere to drug-likeness criteria, thus presenting promising candidates for further development as antiviral agents against influenza A virus infections.

Brain Tumor Segmentation from MRI Images Using Handcrafted Convolutional Neural Network.

Brain tumor segmentation from magnetic resonance imaging (MRI) scans is critical for the diagnosis, treatment planning, and monitoring of therapeutic outcomes. Thus, this research introduces a novel hybrid approach that combines handcrafted features with convolutional neural networks (CNNs) to enhance the performance of brain tumor segmentation. In this study, handcrafted features were extracted from MRI scans that included intensity-based, texture-based, and shape-based features. In parallel, a unique CNN architecture was developed and trained to detect the features from the data automatically. The proposed hybrid method was combined with the handcrafted features and the features identified by CNN in different pathways to a new CNN. In this study, the Brain Tumor Segmentation (BraTS) challenge dataset was used to measure the performance using a variety of assessment measures, for instance, segmentation accuracy, dice score, sensitivity, and specificity. The achieved results showed that our proposed approach outperformed the traditional handcrafted feature-based and individual CNN-based methods used for brain tumor segmentation. In addition, the incorporation of handcrafted features enhanced the performance of CNN, yielding a more robust and generalizable solution. This research has significant potential for real-world clinical applications where precise and efficient brain tumor segmentation is essential. Future research directions include investigating alternative feature fusion techniques and incorporating additional imaging modalities to further improve the proposed method's performance.

Exploring the natural products chemical space through a molecular search to discover potential inhibitors that target the hypoxia-inducible factor (HIF) prolyl hydroxylase domain (PHD).

Introduction: Hypoxia-inducible factor (HIF) prolyl hydroxylase domain (PHD) enzymes are major therapeutic targets of anemia and ischemic/hypoxia diseases. To overcome safety issues, liver failure, and problems associated with on-/off-targets, natural products due to their novel and unique structures offer promising alternatives as drug targets. Methods: In the current study, the Marine Natural Products, North African, South African, East African, and North-East African chemical space was explored for HIF-PHD inhibitors discovery through molecular search, and the final hits were validated using molecular simulation and free energy calculation approaches. Results: Our results revealed that CMNPD13808 with a docking score of -8.690 kcal/mol, CID15081178 with a docking score of -8.027 kcal/mol, CID71496944 with a docking score of -8.48 kcal/mol and CID11821407 with a docking score of -7.78 kcal/mol possess stronger activity than the control N-[(4-hydroxy-8-iodoisoquinolin-3-yl)carbonyl]glycine, 4HG (-6.87 kcal/mol). Interaction analysis revealed that the target compounds interact with Gln239, Tyr310, Tyr329, Arg383 and Trp389 residues, and chelate the active site iron in a bidentate manner in PHD2. Molecular simulation revealed that these target hits robustly block the PHD2 active site by demonstrating stable dynamics. Furthermore, the half-life of the Arg383 hydrogen bond with the target ligands, which is an important factor for PHD2 inhibition, remained almost constant in all the complexes during the simulation. Finally, the total binding free energy of each complex was calculated as CMNPD13808-PHD2 -72.91 kcal/mol, CID15081178-PHD2 -65.55 kcal/mol, CID71496944-PHD2 -68.47 kcal/mol, and CID11821407-PHD2 -62.06 kcal/mol, respectively. Conclusion: The results show the compounds possess good activity in contrast to the control drug (4HG) and need further in vitro and in vivo validation for possible usage as potential drugs against HIF-PHD2-associated diseases.

Pharmacotherapeutic Potential of Natural Products to Target the SARS-CoV-2 PLpro Using Molecular Screening and Simulation Approaches.

Because of the essential role of PLpro in the regulation of replication and dysregulation of the host immune sensing, it is considered a therapeutic target for novel drug development. To reduce the risk of immune evasion and vaccine effectiveness, small molecular therapeutics are the best complementary approach. Hence, we used a structure-based drug-designing approach to identify potential small molecular inhibitors for PLpro of SARS-CoV-2. Initial scoring and re-scoring of the best hits revealed that three compounds NPC320891 (2,2-Dihydroxyindene-1,3-Dione), NPC474594 (Isonarciclasine), and NPC474595 (7-Deoxyisonarciclasine) exhibit higher docking scores than the control GRL0617. Investigation of the binding modes revealed that alongside the essential contacts, i.e., Asp164, Glu167, Tyr264, and Gln269, these molecules also target Lys157 and Tyr268 residues in the active site. Moreover, molecular simulation demonstrated that the reported top hits also possess stable dynamics and structural packing. Furthermore, the residues' flexibility revealed that all the complexes demonstrated higher flexibility in the regions 120-140, 160-180, and 205-215. The 120-140 and 160-180 lie in the finger region of PLpro, which may open/close during the simulation to cover the active site and push the ligand inside. In addition, the total binding free energy was reported to be - 32.65 ± 0.17 kcal/mol for the GRL0617-PLpro, for the NPC320891-PLpro complex, the TBE was - 35.58 ± 0.14 kcal/mol, for the NPC474594-PLpro, the TBE was - 43.72 ± 0.22 kcal/mol, while for NPC474595-PLpro complex, the TBE was calculated to be - 41.61 ± 0.20 kcal/mol, respectively. Clustering of the protein's motion and FEL further revealed that in NPC474594 and NPC474595 complexes, the drug was seen to have moved inside the binding cavity along with the loop in the palm region harboring the catalytic triad, thus justifying the higher binding of these two molecules particularly. In conclusion, the overall results reflect favorable binding of the identified hits strongly than the control drug, thus demanding in vitro and in vivo validation for clinical purposes.

Deep GRU-CNN Model for COVID-19 Detection From Chest X-Rays Data.

In the current era, data is growing exponentially due to advancements in smart devices. Data scientists apply a variety of learning-based techniques to identify underlying patterns in the medical data to address various health-related issues. In this context, automated disease detection has now become a central concern in medical science. Such approaches can reduce the mortality rate through accurate and timely diagnosis. COVID-19 is a modern virus that has spread all over the world and is affecting millions of people. Many countries are facing a shortage of testing kits, vaccines, and other resources due to significant and rapid growth in cases. In order to accelerate the testing process, scientists around the world have sought to create novel methods for the detection of the virus. In this paper, we propose a hybrid deep learning model based on a convolutional neural network (CNN) and gated recurrent unit (GRU) to detect the viral disease from chest X-rays (CXRs). In the proposed model, a CNN is used to extract features, and a GRU is used as a classifier. The model has been trained on 424 CXR images with 3 classes (COVID-19, Pneumonia, and Normal). The proposed model achieves encouraging results of 0.96, 0.96, and 0.95 in terms of precision, recall, and f1-score, respectively. These findings indicate how deep learning can significantly contribute to the early detection of COVID-19 in patients through the analysis of X-ray scans. Such indications can pave the way to mitigate the impact of the disease. We believe that this model can be an effective tool for medical practitioners for early diagnosis.

Survival Prediction of Children Undergoing Hematopoietic Stem Cell Transplantation Using Different Machine Learning Classifiers by Performing Chi-Square Test and Hyperparameter Optimization: A Retrospective Analysis.

Bone marrow transplant (BMT) is an effective surgical treatment for bone marrow-related disorders. However, several associated risk factors can impair long-term survival after BMT. Machine learning (ML) technologies have been proven useful in survival prediction of BMT receivers along with the influences that limit their resilience. In this study, an efficient classification model predicting the survival of children undergoing BMT is presented using a public dataset. Several supervised ML methods were investigated in this regard with an 80-20 train-test split ratio. To ensure prediction with minimal time and resources, only the top 11 out of the 59 dataset features were considered using Chi-square feature selection method. Furthermore, hyperparameter optimization (HPO) using the grid search cross-validation (GSCV) technique was adopted to increase the accuracy of prediction. Four experiments were conducted utilizing a combination of default and optimized hyperparameters on the original and reduced datasets. Our investigation revealed that the top 11 features of HPO had the same prediction accuracy (94.73%) as the entire dataset with default parameters, however, requiring minimal time and resources. Hence, the proposed approach may aid in the development of a computer-aided diagnostic system with satisfactory accuracy and minimal computation time by utilizing medical data records.

Blocking key mutated hotspot residues in the RBD of the omicron variant (B.1.1.529) with medicinal compounds to disrupt the RBD-hACE2 complex using molecular screening and simulation approaches.

A new variant of SARS-CoV-2 known as the omicron variant (B.1.1.529) reported in South Africa with 30 mutations in the whole spike protein, among which 15 mutations are in the receptor-binding domain, is continuously spreading exponentially around the world. The omicron variant is reported to be highly contagious with antibody-escaping activity. The emergence of antibody-escaping variants is alarming, and thus the quick discovery of small molecule inhibitors is needed. Hence, the current study uses computational drug screening and molecular dynamics simulation approaches (replicated) to identify novel drugs that can inhibit the binding of the receptor-binding domain (RBD) with hACE2. Screening of the North African, East African and North-East African medicinal compound databases by employing a multi-step screening approach revealed four compounds, namely (-)-pipoxide (C1), 2-(p-hydroxybenzyl) benzofuran-6-ol (C2), 1-(4-hydroxy-3-methoxyphenyl)-2-{4-[(E)-3-hydroxy-1-propenyl]-2-methoxyphenoxy}-1,3-propanediol (C3), and Rhein (C4), with excellent anti-viral properties against the RBD of the omicron variant. Investigation of the dynamics demonstrates stable behavior, good residue flexibility profiles, and structural compactness. Validation of the top hits using computational bioactivity analysis, binding free energy calculations and dissociation constant (K D) analysis also indicated the anti-viral properties of these compounds. In conclusion, this study will help in the design and discovery of novel drug therapeutics, which may be used against the emerging omicron variant of SARS-CoV-2.

Predictors of Poor Response and Adverse Events Following Botulinum Toxin A for Refractory Idiopathic Overactive Bladder: A Systematic Review.

CONTEXT: Botulinum toxin A (BTX-A) injections are effective in managing refractory overactive bladder (OAB). However, some patients exhibit a poor response and/or experience adverse events (AEs) such as voiding dysfunction necessitating clean intermittent self-catheterisation (CISC) and urinary tract infections (UTIs). OBJECTIVE: To systematically evaluate whether poor response/AEs to BTX-A for idiopathic OAB are predictable. EVIDENCE ACQUISITION: MEDLINE, EMBASE, and Google Scholar database were searched in March 2020. Studies reporting predictive factors for poor response or AEs were included. Two reviewers independently screened articles, searched references, and extracted data. Risk of bias (Quality in Prognosis Studies [QUIPS]) and quality of evidence (Grading of Recommendations Assessment, Development and Evaluation [GRADE]) tools were utilised. EVIDENCE SYNTHESIS: Of 1579 articles, 17 met the inclusion criteria. These were cohort studies with predominantly level 3 evidence. Factors including male gender, frailty, comorbidity, increasing age, smoking, baseline leakage episodes, and various urodynamic parameters (bladder outlet obstruction index [BOOI], high pretreatment maximum detrusor pressure, and poor bladder compliance) were proposed as predictors of nonresponse. In predicting CISC use, male gender, comorbidity, increasing age, number of vaginal deliveries, hysterectomy, and urodynamic parameters (bladder capacity, postvoid residual volume, projected isovolumetric pressure value, bladder contractility index, and BOOI) were implicated. Female gender, males with their prostates in situ, and CISC were suggested to increase UTIs after BTX-A. CONCLUSIONS: This review has identified factors that may predict poor response/AEs following bladder BTX-A and help in counselling of patients. Overall, the quality of individual studies included was poor, limiting the certainty of evidence reported. Larger-scale, better-designed trials with uniform definitions of poor response are required to confirm these preliminary findings. PATIENT SUMMARY: This review assessed whether we could predict poor response or side effects to bladder botulinum toxin A injections in managing overactive bladder. Many different factors based on the patient, medical conditions, previous surgery, and pretreatment investigations were identified. However, the quality of included studies was generally poor, limiting their conclusions.

Total Pelvic Exenteration for Locally Advanced and Recurrent Rectal Cancer: Urological Outcomes and Adverse Events.

BACKGROUND: Little has been reported on urological complications of total pelvic exenteration (TPE) for locally advanced or recurrent rectal cancer. OBJECTIVE: To assess urological reconstructive outcomes and adverse events in this setting. DESIGN, SETTING, AND PARTICIPANTS: A total of 104 patients underwent TPE from 2004 to 2016 in this single-centre, retrospective study. Electronic and paper records were evaluated for data extraction. Mean follow-up was 36.5 mo. INTERVENTION: TPE. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Urological complications were analysed using two-tailed t and chi-square tests, binary logistic regression analysis. RESULTS AND LIMITATIONS: Sixty-three (61%) patients received radiotherapy prior to TPE. Incontinent diversions included ileal conduit (n = 95), colonic conduits (n = 4), wet colostomy (n = 1), and cutaneous ureterostomy (n = 1). Three patients had a continent diversion. The overall urological complication rate was 54%. According to Clavien-Dindo classification, 30 patients, five patients, and one patient had grade III, IV, and V complications, respectively. The commonest complication was urinary tract infection (in 32 [31%] patients). Anastomotic leaks were seen in 14 (13%) cases, of which eight (8%) were urinary leaks. Fistulas were seen in three (3%) patients, involving the urinary system. A return to theatre was required in 12 (12%) patients. Ureteroenteric strictures were seen in seven (7%). No differences were seen in urological outcomes in patients with primary or recurrent rectal cancer (p = 0.69), or by radiation status (p = 0.24). The main limitation is the retrospective nature of the study. CONCLUSIONS: TPE is complex with recognised high risk of morbidity. In this cohort, there was no significant difference in outcomes between primary and recurrent disease, and surgery after radiation. PATIENT SUMMARY: In this study, we assessed urological complications following total pelvic exenteration. Urinary complications affected more than half of patients. Urinary tract infection is the commonest risk. Approximately one-third of patients required surgical, radiological, or endoscopic intervention ± intensive care admission. Radiation prior to the operation did not affect urinary complications.

Predictors of Poor Response and Adverse Events Following Botulinum Toxin-A for Refractory Idiopathic Overactive Bladder.

OBJECTIVE: To ascertain whether a poor response and adverse events (voiding dysfunction and urinary tract infection) were predictable for first time botulinum toxin-A (BTX-A) injections in a patient cohort of refractory idiopathic overactive bladder with detrusor overactivity. METHODS: Patients who received BTX-A injections for the first time between the dates of March 2004-August 2017 were analyzed in this single center study. Urogenital Distress Inventory short form (UDI-6) questionnaires were collected both preinjection and postinjection prospectively. A poor response was defined as a decrease of less than 16.7 on the UDI-6 questionnaire. Additional information was gathered from patient records in a retrospective fashion. Predictors of poor response, voiding dysfunction, and UTI were analyzed with multivariate logistic regression analysis. RESULTS: Seventy-four patients were analyzed. The only predictor of poor response was male gender (OR, 5.45; 95% CI 1.83-16.47; P = .002). Lower maximum urinary flow rates (OR, 0.91; 95% CI, 0.83-0.99; P = .023), male gender (OR, 5.14; 95% CI 1.41-18.72; P = .013), and hysterectomy in females (OR, 4.55; 95% CI, 1.09-18.87; P = .038) were predictors of clean intermittent self catheterisation (CISC). There was an increased risk of UTIs in patients who performed CISC (OR, 5.26; 95% CI 1.38-20.0; P = .015). CONCLUSION: Male gender was associated with a poor response to BTX-A injections and increased risk of CISC. Lower maximum urinary flow rates and women with hysterectomies were at increased risk of requiring CISC postinjection. Performing CISC was associated with increased risk of UTI. These factors could be helpful when counselling or selecting patients.

An Integrated Systems Biology and Network-Based Approaches to Identify Novel Biomarkers in Breast Cancer Cell Lines Using Gene Expression Data.

Breast cancer is the most common cause of death in women worldwide. Approximately 5%-10% of instances are attributed to mutations acquired from the parents. Therefore, it is highly recommended to design more potential drugs and drug targets to eradicate such complex diseases. Network-based gene expression profiling is a suggested tool for discovering drug targets by incorporating various factors such as disease states, intensities based on gene expression as well as protein-protein interactions. To find prospective biomarkers in breast cancer, we first identified differentially expressed genes (DEGs) statistical methods p-value and false discovery rate were initially used. Of the total 82 DEGs, 67 were upregulated while the remaining 17 were downregulated. Sub-modules and hub genes include VEGFA with the highest degree, followed by 15 CCND1 and CXCL8 with 12-degree score was found. The survival analysis revealed that all the hub genes have important role in the development and progression of breast cancer. Enrichment analysis revealed that most of these genes are involved in signaling pathways and in the extracellular spaces. We also identified transcription factors and kinases, which regulate proteins in the DEGs PPI. Finally, drugs for each hub genes were identified. These results further expanded the knowledge regarding important biomarkers in breast cancer.

Immunoinformatics approaches to explore Helicobacter Pylori proteome (Virulence Factors) to design B and T cell multi-epitope subunit vaccine.

Helicobacter Pylori is a known causal agent of gastric malignancies and peptic ulcers. The extremophile nature of this bacterium is protecting it from designing a potent drug against it. Therefore, the use of computational approaches to design antigenic, stable and safe vaccine against this pathogen could help to control the infections associated with it. Therefore, in this study, we used multiple immunoinformatics approaches along with other computational approaches to design a multi-epitopes subunit vaccine against H. Pylori. A total of 7 CTL and 12 HTL antigenic epitopes based on c-terminal cleavage and MHC binding scores were predicted from the four selected proteins (CagA, OipA, GroEL and cagA). The predicted epitopes were joined by AYY and GPGPG linkers. Β-defensins adjuvant was added to the N-terminus of the vaccine. For validation, immunogenicity, allergenicity and physiochemical analysis were conducted. The designed vaccine is likely antigenic in nature and produced robust and substantial interactions with Toll-like receptors (TLR-2, 4, 5, and 9). The vaccine developed was also subjected to an in silico cloning and immune response prediction model, which verified its efficiency of expression and the immune system provoking response. These analyses indicate that the suggested vaccine may produce particular immune responses against H. pylori, but laboratory validation is needed to verify the safety and immunogenicity status of the suggested vaccine design.