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  1. Article: AntiBP3: A Method for Predicting Antibacterial Peptides against Gram-Positive/Negative/Variable Bacteria.

    Bajiya, Nisha / Choudhury, Shubham / Dhall, Anjali / Raghava, Gajendra P S

    Antibiotics (Basel, Switzerland)

    2024  Volume 13, Issue 2

    Abstract: Most of the existing methods developed for predicting antibacterial peptides (ABPs) are mostly designed to target either gram-positive or gram-negative bacteria. In this study, we describe a method that allows us to predict ABPs against gram-positive, ... ...

    Abstract Most of the existing methods developed for predicting antibacterial peptides (ABPs) are mostly designed to target either gram-positive or gram-negative bacteria. In this study, we describe a method that allows us to predict ABPs against gram-positive, gram-negative, and gram-variable bacteria. Firstly, we developed an alignment-based approach using BLAST to identify ABPs and achieved poor sensitivity. Secondly, we employed a motif-based approach to predict ABPs and obtained high precision with low sensitivity. To address the issue of poor sensitivity, we developed alignment-free methods for predicting ABPs using machine/deep learning techniques. In the case of alignment-free methods, we utilized a wide range of peptide features that include different types of composition, binary profiles of terminal residues, and fastText word embedding. In this study, a five-fold cross-validation technique has been used to build machine/deep learning models on training datasets. These models were evaluated on an independent dataset with no common peptide between training and independent datasets. Our machine learning-based model developed using the amino acid binary profile of terminal residues achieved maximum AUC 0.93, 0.98, and 0.94 for gram-positive, gram-negative, and gram-variable bacteria, respectively, on an independent dataset. Our method performs better than existing methods when compared with existing approaches on an independent dataset. A user-friendly web server, standalone package and pip package have been developed to facilitate peptide-based therapeutics.
    Language English
    Publishing date 2024-02-08
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2681345-2
    ISSN 2079-6382
    ISSN 2079-6382
    DOI 10.3390/antibiotics13020168
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: In Silico Tool for Identification, Designing, and Searching of IL13-Inducing Peptides in Antigens.

    Jain, Shipra / Dhall, Anjali / Patiyal, Sumeet / Raghava, Gajendra P S

    Methods in molecular biology (Clifton, N.J.)

    2023  Volume 2673, Page(s) 329–338

    Abstract: Interleukins are a distinctive class of molecules exhibiting various immune signaling functions. Immunoregulatory cytokine, Interleukin 13 (IL13), is primarily synthesized by activated T-helper 2 cells, mast cells, and basophils. IL13, is known to ... ...

    Abstract Interleukins are a distinctive class of molecules exhibiting various immune signaling functions. Immunoregulatory cytokine, Interleukin 13 (IL13), is primarily synthesized by activated T-helper 2 cells, mast cells, and basophils. IL13, is known to stimulate many allergic and autoimmune diseases, such as asthma, rheumatoid arthritis, systemic sclerosis, ulcerative colitis, airway hyperresponsiveness, glycoprotein hypersecretion, and goblet cell hyperplasia. In addition to such disorders, IL13 also leads to carcinogenesis by inhibiting tumor immunosurveillance. Due to its role in various diseases, predicting IL13-inducing peptides or regions in a protein is vital to designing safe protein vaccines and therapeutics. IL13pred is an in silico tool which aids in identifying, predicting, and designing IL13-inducing peptides. The IL13pred web server and standalone package is easily accessible at ( https://webs.iiitd.edu.in/raghava/il13pred/ ).
    MeSH term(s) Humans ; Interleukin-13 ; Cytokines ; Interleukins ; Peptides ; Asthma
    Chemical Substances Interleukin-13 ; Cytokines ; Interleukins ; Peptides
    Language English
    Publishing date 2023-05-31
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-3239-0_23
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Risk assessment of cancer patients based on HLA-I alleles, neobinders and expression of cytokines.

    Dhall, Anjali / Patiyal, Sumeet / Kaur, Harpreet / Raghava, Gajendra P S

    Computers in biology and medicine

    2023  Volume 167, Page(s) 107594

    Abstract: Advancements in cancer immunotherapy have shown significant outcomes in treating cancers. To design effective immunotherapy, it's important to understand immune response of a patient based on its genomic profile. However, analyses to do that requires ... ...

    Abstract Advancements in cancer immunotherapy have shown significant outcomes in treating cancers. To design effective immunotherapy, it's important to understand immune response of a patient based on its genomic profile. However, analyses to do that requires proficiency in the bioinformatic methods. Swiftly growing sequencing technologies and statistical methods create a blockage for the scientists who want to find the biomarkers for different cancers but don't have detailed knowledge of coding or tool. Here, we are providing a web-based resource that gives scientists with no bioinformatics expertise, the ability to obtain the prognostic biomarkers for different cancer types at different levels. We computed prognostic biomarkers from 8346 cancer patients for twenty cancer types. These biomarkers were computed based on i) presence of 352 Human leukocyte antigen class-I, ii) 660959 tumor-specific HLA1 neobinders, and iii) expression profile of 153 cytokines. It was observed that survival risk of cancer patients depends on presence of certain type of HLA-I alleles; for example, liver hepatocellular carcinoma patients with HLA-A*03:01 are at lower risk. Our analysis indicates that neobinders of HLA-I alleles have high correlation with overall survival of certain type of cancer patients. For example, HLA-B*07:02 binders have 0.49 correlation with survival of lung squamous cell carcinoma and -0.77 with kidney chromophobe patients. Additionally, we computed prognostic biomarkers based on cytokine expressions. Higher expression of few cytokines is survival favorable like IL-2 for bladder urothelial carcinoma, whereas IL-5R is survival unfavorable for kidney chromophobe patients. Freely accessible to public, CancerHLA-I maintains raw and analysed data (https://webs.iiitd.edu.in/raghava/cancerhla1/).
    MeSH term(s) Humans ; Cytokines/genetics ; Alleles ; Carcinoma, Transitional Cell/genetics ; Urinary Bladder Neoplasms/genetics ; Biomarkers ; Lung Neoplasms/genetics ; Risk Assessment
    Chemical Substances Cytokines ; Biomarkers
    Language English
    Publishing date 2023-10-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 127557-4
    ISSN 1879-0534 ; 0010-4825
    ISSN (online) 1879-0534
    ISSN 0010-4825
    DOI 10.1016/j.compbiomed.2023.107594
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Prediction of celiac disease associated epitopes and motifs in a protein.

    Tomer, Ritu / Patiyal, Sumeet / Dhall, Anjali / Raghava, Gajendra P S

    Frontiers in immunology

    2023  Volume 14, Page(s) 1056101

    Abstract: Introduction: Celiac disease (CD) is an autoimmune gastrointestinal disorder causes immune-mediated enteropathy against gluten. Gluten immunogenic peptides have the potential to trigger immune responses which leads to damage the small intestine. HLA-DQ2/ ...

    Abstract Introduction: Celiac disease (CD) is an autoimmune gastrointestinal disorder causes immune-mediated enteropathy against gluten. Gluten immunogenic peptides have the potential to trigger immune responses which leads to damage the small intestine. HLA-DQ2/DQ8 are major alleles that bind to epitope/antigenic region of gluten and induce celiac disease. There is a need to identify CD associated epitopes in protein-based foods and therapeutics.
    Methods: In this study, computational tools have been developed to predict CD associated epitopes and motifs. Dataset used for training, testing and evaluation contain experimentally validated CD associated and non-CD associate peptides. We perform positional analysis to identify the most significant position of an amino acid residue in the peptide and checked the frequency of HLA alleles. We also compute amino acid composition to develop machine learning based models. We also developed ensemble method that combines motif-based approach and machine learning based models.
    Results and discussion: Our analysis support existing hypothesis that proline (P) and glutamine (Q) are highly abundant in CD associated peptides. A model based on density of P&Q in peptides has been developed for predicting CD associated peptides which achieve maximum AUROC 0.98 on independent data. We discovered motifs (e.g., QPF, QPQ, PYP) which occurs specifically in CD associated peptides. We also developed machine learning based models using peptide composition and achieved maximum AUROC 0.99. Finally, we developed ensemble method that combines motif-based approach and machine learning based models. The ensemble model-predict CD associated motifs with 100% accuracy on an independent dataset, not used for training. Finally, the best models and motifs has been integrated in a web server and standalone software package "CDpred". We hope this server anticipate the scientific community for the prediction, designing and scanning of CD associated peptides as well as CD associated motifs in a protein/peptide sequence (https://webs.iiitd.edu.in/raghava/cdpred/).
    MeSH term(s) Humans ; Celiac Disease ; Epitopes ; Glutens ; Peptides ; Amino Acids
    Chemical Substances Epitopes ; Glutens (8002-80-0) ; Peptides ; Amino Acids
    Language English
    Publishing date 2023-01-19
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1056101
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Prediction of risk-associated genes and high-risk liver cancer patients from their mutation profile: benchmarking of mutation calling techniques.

    Patiyal, Sumeet / Dhall, Anjali / Raghava, Gajendra P S

    Biology methods & protocols

    2022  Volume 7, Issue 1, Page(s) bpac012

    Abstract: Identification of somatic mutations with high precision is one of the major challenges in the prediction of high-risk liver cancer patients. In the past, number of mutations calling techniques has been developed that include MuTect2, MuSE, Varscan2, and ... ...

    Abstract Identification of somatic mutations with high precision is one of the major challenges in the prediction of high-risk liver cancer patients. In the past, number of mutations calling techniques has been developed that include MuTect2, MuSE, Varscan2, and SomaticSniper. In this study, an attempt has been made to benchmark the potential of these techniques in predicting the prognostic biomarkers for liver cancer. Initially, we extracted somatic mutations in liver cancer patients using Variant Call Format (VCF) and Mutation Annotation Format (MAF) files from the cancer genome atlas. In terms of size, the MAF files are 42 times smaller than VCF files and containing only high-quality somatic mutations. Furthermore, machine learning-based models have been developed for predicting high-risk cancer patients using mutations obtained from different techniques. The performance of different techniques and data files has been compared based on their potential to discriminate high- and low-risk liver cancer patients. Based on correlation analysis, we selected 80 genes having significant negative correlation with the overall survival of liver cancer patients. The univariate survival analysis revealed the prognostic role of highly mutated genes. Single gene-based analysis showed that MuTect2 technique-based MAF file has achieved maximum hazard ratio (HR
    Language English
    Publishing date 2022-05-27
    Publishing country England
    Document type Journal Article
    ISSN 2396-8923
    ISSN (online) 2396-8923
    DOI 10.1093/biomethods/bpac012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: A deep learning-based method for the prediction of DNA interacting residues in a protein.

    Patiyal, Sumeet / Dhall, Anjali / Raghava, Gajendra P S

    Briefings in bioinformatics

    2022  Volume 23, Issue 5

    Abstract: DNA-protein interaction is one of the most crucial interactions in the biological system, which decides the fate of many processes such as transcription, regulation and splicing of genes. In this study, we trained our models on a training dataset of 646 ... ...

    Abstract DNA-protein interaction is one of the most crucial interactions in the biological system, which decides the fate of many processes such as transcription, regulation and splicing of genes. In this study, we trained our models on a training dataset of 646 DNA-binding proteins having 15 636 DNA interacting and 298 503 non-interacting residues. Our trained models were evaluated on an independent dataset of 46 DNA-binding proteins having 965 DNA interacting and 9911 non-interacting residues. All proteins in the independent dataset have less than 30% of sequence similarity with proteins in the training dataset. A wide range of traditional machine learning and deep learning (1D-CNN) techniques-based models have been developed using binary, physicochemical properties and Position-Specific Scoring Matrix (PSSM)/evolutionary profiles. In the case of machine learning technique, eXtreme Gradient Boosting-based model achieved a maximum area under the receiver operating characteristics (AUROC) curve of 0.77 on the independent dataset using PSSM profile. Deep learning-based model achieved the highest AUROC of 0.79 on the independent dataset using a combination of all three profiles. We evaluated the performance of existing methods on the independent dataset and observed that our proposed method outperformed all the existing methods. In order to facilitate scientific community, we developed standalone software and web server, which are accessible from https://webs.iiitd.edu.in/raghava/dbpred.
    MeSH term(s) DNA/chemistry ; DNA/genetics ; DNA-Binding Proteins ; Databases, Protein ; Deep Learning ; Position-Specific Scoring Matrices
    Chemical Substances DNA-Binding Proteins ; DNA (9007-49-2)
    Language English
    Publishing date 2022-08-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 2068142-2
    ISSN 1477-4054 ; 1467-5463
    ISSN (online) 1477-4054
    ISSN 1467-5463
    DOI 10.1093/bib/bbac322
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: HLAncPred: a method for predicting promiscuous non-classical HLA binding sites.

    Dhall, Anjali / Patiyal, Sumeet / Raghava, Gajendra P S

    Briefings in bioinformatics

    2022  Volume 23, Issue 5

    Abstract: Human leukocyte antigens (HLA) regulate various innate and adaptive immune responses and play a crucial immunomodulatory role. Recent studies revealed that non-classical HLA-(HLA-E & HLA-G) based immunotherapies have many advantages over traditional HLA- ... ...

    Abstract Human leukocyte antigens (HLA) regulate various innate and adaptive immune responses and play a crucial immunomodulatory role. Recent studies revealed that non-classical HLA-(HLA-E & HLA-G) based immunotherapies have many advantages over traditional HLA-based immunotherapy, particularly against cancer and COVID-19 infection. In the last two decades, several methods have been developed to predict the binders of classical HLA alleles. In contrast, limited attempts have been made to develop methods for predicting non-classical HLA binding peptides, due to the scarcity of sufficient experimental data. Of note, in order to facilitate the scientific community, we have developed an artificial intelligence-based method for predicting binders of class-Ib HLA alleles. All the models were trained and tested on experimentally validated data obtained from the recent release of IEDB. The machine learning models achieved more than 0.98 AUC for HLA-G alleles on validation dataset. Similarly, our models achieved the highest AUC of 0.96 and 0.94 on the validation dataset for HLA-E*01:01 and HLA-E*01:03, respectively. We have summarized the models developed in the past for non-classical HLA and validated the performance with the models developed in this study. Moreover, to facilitate the community, we have utilized our tool for predicting the potential non-classical HLA binding peptides in the spike protein of different variants of virus causing COVID-19, including Omicron (B.1.1.529). One of the major challenges in the field of immunotherapy is to identify the promiscuous binders or antigenic regions that can bind to a large number of HLA alleles. To predict the promiscuous binders for the non-classical HLA alleles, we developed a web server HLAncPred (https://webs.iiitd.edu.in/raghava/hlancpred) and standalone package.
    MeSH term(s) Artificial Intelligence ; Binding Sites ; COVID-19/genetics ; HLA-G Antigens/metabolism ; Humans ; Peptides/chemistry ; Protein Binding ; Spike Glycoprotein, Coronavirus/metabolism
    Chemical Substances HLA-G Antigens ; Peptides ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
    Language English
    Publishing date 2022-06-01
    Publishing country England
    Document type Journal Article
    ZDB-ID 2068142-2
    ISSN 1477-4054 ; 1467-5463
    ISSN (online) 1477-4054
    ISSN 1467-5463
    DOI 10.1093/bib/bbac192
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: A Web-Based Method for the Identification of IL6-Based Immunotoxicity in Vaccine Candidates.

    Dhall, Anjali / Patiyal, Sumeet / Sharma, Neelam / Usmani, Salman Sadullah / Raghava, Gajendra P S

    Methods in molecular biology (Clifton, N.J.)

    2023  Volume 2673, Page(s) 317–327

    Abstract: Interleukin 6 (IL6) is a major pro-inflammatory cytokine that plays a pivotal role in both innate and adaptive immune responses. In the past, a number of studies reported that high level of IL6 promotes the proliferation of cancer, autoimmune disorders, ... ...

    Abstract Interleukin 6 (IL6) is a major pro-inflammatory cytokine that plays a pivotal role in both innate and adaptive immune responses. In the past, a number of studies reported that high level of IL6 promotes the proliferation of cancer, autoimmune disorders, and cytokine storm in COVID-19 patients. Thus, it is extremely important to identify and remove the antigenic regions from a therapeutic protein or vaccine candidate that may induce IL6-associated immunotoxicity. In order to overcome this challenge, our group has developed a computational tool, IL6pred, for discovering IL6-inducing peptides in a vaccine candidate. The aim of this chapter is to describe the potential applications and methodology of IL6pred. It sheds light on the prediction, designing, and scanning modules of IL6pred webserver and standalone package ( https://webs.iiitd.edu.in/raghava/il6pred/ ).
    MeSH term(s) Humans ; Interleukin-6/genetics ; COVID-19/prevention & control ; Cytokines/metabolism ; Vaccines ; Internet
    Chemical Substances Interleukin-6 ; Cytokines ; Vaccines
    Language English
    Publishing date 2023-05-31
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-3239-0_22
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: An ensemble method for prediction of phage-based therapy against bacterial infections.

    Aggarwal, Suchet / Dhall, Anjali / Patiyal, Sumeet / Choudhury, Shubham / Arora, Akanksha / Raghava, Gajendra P S

    Frontiers in microbiology

    2023  Volume 14, Page(s) 1148579

    Abstract: Phage therapy is a viable alternative to antibiotics for treating microbial infections, particularly managing drug-resistant strains of bacteria. One of the major challenges in designing phage-based therapy is to identify the most appropriate potential ... ...

    Abstract Phage therapy is a viable alternative to antibiotics for treating microbial infections, particularly managing drug-resistant strains of bacteria. One of the major challenges in designing phage-based therapy is to identify the most appropriate potential phage candidate to treat bacterial infections. In this study, an attempt has been made to predict phage-host interactions with high accuracy to identify the potential bacteriophage that can be used for treating a bacterial infection. The developed models have been created using a training dataset containing 826 phage- host interactions, and have been evaluated on a validation dataset comprising 1,201 phage-host interactions. Firstly, alignment-based models have been developed using similarity between phage-phage (BLASTPhage), host-host (BLASTHost) and phage-CRISPR (CRISPRPred), where we achieved accuracy between 42.4-66.2% for BLASTPhage, 55-78.4% for BLASTHost, and 43.7-80.2% for CRISPRPred across five taxonomic levels. Secondly, alignment free models have been developed using machine learning techniques. Thirdly, hybrid models have been developed by integrating the alignment-free models and the similarity-scores where we achieved maximum performance of (60.6-93.5%). Finally, an ensemble model has been developed that combines the hybrid and alignment-based models. Our ensemble model achieved highest accuracy of 67.9, 80.6, 85.5, 90, and 93.5% at Genus, Family, Order, Class, and Phylum levels on validation dataset. In order to serve the scientific community, we have also developed a webserver named PhageTB and provided a standalone software package (https://webs.iiitd.edu.in/raghava/phagetb/) for the same.
    Language English
    Publishing date 2023-03-23
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2023.1148579
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: TNFepitope: A webserver for the prediction of TNF-α inducing epitopes.

    Dhall, Anjali / Patiyal, Sumeet / Choudhury, Shubham / Jain, Shipra / Narang, Kashish / Raghava, Gajendra P S

    Computers in biology and medicine

    2023  Volume 160, Page(s) 106929

    Abstract: Tumor Necrosis Factor alpha (TNF-α) is a pleiotropic pro-inflammatory cytokine that is crucial in controlling the signaling pathways within the immune cells. Recent studies reported that higher expression levels of TNF-α are associated with the ... ...

    Abstract Tumor Necrosis Factor alpha (TNF-α) is a pleiotropic pro-inflammatory cytokine that is crucial in controlling the signaling pathways within the immune cells. Recent studies reported that higher expression levels of TNF-α are associated with the progression of several diseases, including cancers, cytokine release syndrome in COVID-19, and autoimmune disorders. Thus, it is the need of the hour to develop immunotherapies or subunit vaccines to manage TNF-α progression in various disease conditions. In the pilot study, we proposed a host-specific in-silico tool for predicting, designing, and scanning TNF-α inducing epitopes. The prediction models were trained and validated on the experimentally validated TNF-α inducing/non-inducing epitopes from human and mouse hosts. Firstly, we developed alignment-free (machine learning based models using composition-based features of peptides) methods for predicting TNF-α inducing peptides and achieved maximum AUROC of 0.79 and 0.74 for human and mouse hosts, respectively. Secondly, an alignment-based (using BLAST) method has been used for predicting TNF-α inducing epitopes. Finally, a hybrid method (combination of alignment-free and alignment-based method) has been developed for predicting epitopes. Hybrid approach achieved maximum AUROC of 0.83 and 0.77 on an independent dataset for human and mouse hosts, respectively. We have also identified potential TNF-α inducing peptides in different proteins of HIV-1, HIV-2, SARS-CoV-2, and human insulin. The best models developed in this study has been incorporated in the webserver TNFepitope (https://webs.iiitd.edu.in/raghava/tnfepitope/), standalone package and GitLab (https://gitlab.com/raghavalab/tnfepitope).
    MeSH term(s) Humans ; Animals ; Mice ; Epitopes ; Tumor Necrosis Factor-alpha ; Pilot Projects ; COVID-19 ; SARS-CoV-2 ; Peptides
    Chemical Substances Epitopes ; Tumor Necrosis Factor-alpha ; Peptides
    Language English
    Publishing date 2023-04-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 127557-4
    ISSN 1879-0534 ; 0010-4825
    ISSN (online) 1879-0534
    ISSN 0010-4825
    DOI 10.1016/j.compbiomed.2023.106929
    Database MEDical Literature Analysis and Retrieval System OnLINE

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