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1.
Adv Protein Chem Struct Biol ; 139: 383-403, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38448141

RESUMO

An uncommon opportunistic fungal infection known as mucormycosis is caused by a class of molds called mucoromycetes. Currently, antifungal therapy and surgical debridement are the primary treatment options for mucormycosis. Despite the importance of comprehensive knowledge on mucormycosis, there is a lack of well-annotated databases that provide all relevant information. In this study, we have gathered and organized all available information related to mucormycosis that include disease's genome, proteins, diagnostic methods. Furthermore, using the AlphaFold2.0 prediction tool, we have predicted the tertiary structures of potential drug targets. We have categorized the information into three major sections: "genomics/proteomics," "immunotherapy," and "drugs." The genomics/proteomics module contains information on different strains responsible for mucormycosis. The immunotherapy module includes putative sequence-based therapeutics predicted using established tools. Drugs module provides information on available drugs for treating the disease. Additionally, the drugs module also offers prerequisite information for designing computationally aided drugs, such as putative targets and predicted structures. In order to provide comprehensive information over internet, we developed a web-based platform MucormyDB (https://webs.iiitd.edu.in/raghava/mucormydb/).


Assuntos
Fármacos Anti-HIV , Mucormicose , Humanos , Mucormicose/tratamento farmacológico , Mucormicose/genética , Genômica , Bases de Dados Factuais , Sistemas de Liberação de Medicamentos
2.
Arterioscler Thromb Vasc Biol ; 44(4): 843-865, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38385286

RESUMO

BACKGROUND: Accumulating evidence implicates the activation of G-protein-coupled PARs (protease-activated receptors) by coagulation proteases in the regulation of innate immune responses. METHODS: Using mouse models with genetic alterations of the PAR2 signaling platform, we have explored contributions of PAR2 signaling to infection with coxsackievirus B3, a single-stranded RNA virus provoking multiorgan tissue damage, including the heart. RESULTS: We show that PAR2 activation sustains correlates of severe morbidity-hemodynamic compromise, aggravated hypothermia, and hypoglycemia-despite intact control of the virus. Following acute viral liver injury, canonical PAR2 signaling impairs the restoration process associated with exaggerated type I IFN (interferon) signatures in response to viral RNA recognition. Metabolic profiling in combination with proteomics of liver tissue shows PAR2-dependent reprogramming of liver metabolism, increased lipid droplet storage, and gluconeogenesis. PAR2-sustained hypodynamic compromise, reprograming of liver metabolism, as well as imbalanced IFN responses are prevented in ß-arrestin coupling-deficient PAR2 C-terminal phosphorylation mutant mice. Thus, wiring between upstream proteases and immune-metabolic responses results from biased PAR2 signaling mediated by intracellular recruitment of ß-arrestin. Importantly, blockade of the TF (tissue factor)-FVIIa (coagulation factor VIIa) complex capable of PAR2 proteolysis with the NAPc2 (nematode anticoagulant protein c2) mitigated virus-triggered pathology, recapitulating effects seen in protease cleavage-resistant PAR2 mice. CONCLUSIONS: These data provide insights into a TF-FVIIa signaling axis through PAR2-ß-arrestin coupling that is a regulator of inflammation-triggered tissue repair and hemodynamic compromise in coxsackievirus B3 infection and can potentially be targeted with selective coagulation inhibitors.


Assuntos
Insuficiência de Múltiplos Órgãos , Tromboplastina , Animais , Camundongos , Tromboplastina/metabolismo , beta-Arrestinas/metabolismo , Receptor PAR-2/genética , Fator VIIa/metabolismo , Endopeptidases/metabolismo
3.
Database (Oxford) ; 20232023 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-36747479

RESUMO

Saliva as a non-invasive diagnostic fluid has immense potential as a tool for early diagnosis and prognosis of patients. The information about salivary biomarkers is broadly scattered across various resources and research papers. It is important to bring together all the information on salivary biomarkers to a single platform. This will accelerate research and development in non-invasive diagnosis and prognosis of complex diseases. We collected widespread information on five types of salivary biomarkers-proteins, metabolites, microbes, micro-ribonucleic acid (miRNA) and genes found in humans. This information was collected from different resources that include PubMed, the Human Metabolome Database and SalivaTecDB. Our database SalivaDB contains a total of 15 821 entries for 201 different diseases and 48 disease categories. These entries can be classified into five categories based on the type of biomolecules; 6067, 3987, 2909, 2272 and 586 entries belong to proteins, metabolites, microbes, miRNAs and genes, respectively. The information maintained in this database includes analysis methods, associated diseases, biomarker type, regulation status, exosomal origin, fold change and sequence. The entries are linked to relevant biological databases to provide users with comprehensive information. We developed a web-based interface that provides a wide range of options like browse, keyword search and advanced search. In addition, a similarity search module has been integrated which allows users to perform a similarity search using Basic Local Alignment Search Tool and Smith-Waterman algorithm against biomarker sequences in SalivaDB. We created a web-based database-SalivaDB, which provides information about salivary biomarkers found in humans. A wide range of web-based facilities have been integrated to provide services to the scientific community. https://webs.iiitd.edu.in/raghava/salivadb/.


Assuntos
Bases de Dados Factuais , MicroRNAs , Humanos , Algoritmos , Biomarcadores , MicroRNAs/genética , Software , Saliva
4.
J Comput Biol ; 30(2): 204-222, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36251780

RESUMO

In the last three decades, a wide range of protein features have been discovered to annotate a protein. Numerous attempts have been made to integrate these features in a software package/platform so that the user may compute a wide range of features from a single source. To complement the existing methods, we developed a method, Pfeature, for computing a wide range of protein features. Pfeature allows to compute more than 200,000 features required for predicting the overall function of a protein, residue-level annotation of a protein, and function of chemically modified peptides. It has six major modules, namely, composition, binary profiles, evolutionary information, structural features, patterns, and model building. Composition module facilitates to compute most of the existing compositional features, plus novel features. The binary profile of amino acid sequences allows to compute the fraction of each type of residue as well as its position. The evolutionary information module allows to compute evolutionary information of a protein in the form of a position-specific scoring matrix profile generated using Position-Specific Iterative Basic Local Alignment Search Tool (PSI-BLAST); fit for annotation of a protein and its residues. A structural module was developed for computing of structural features/descriptors from a tertiary structure of a protein. These features are suitable to predict the therapeutic potential of a protein containing non-natural or chemically modified residues. The model-building module allows to implement various machine learning techniques for developing classification and regression models as well as feature selection. Pfeature also allows the generation of overlapping patterns and features from a protein. A user-friendly Pfeature is available as a web server python library and stand-alone package.


Assuntos
Proteínas , Software , Proteínas/química , Peptídeos , Sequência de Aminoácidos , Aprendizado de Máquina , Bases de Dados de Proteínas , Análise de Sequência de Proteína/métodos
5.
Artigo em Inglês | MEDLINE | ID: mdl-35305716

RESUMO

Immunotherapy is a rapidly growing therapy for cancer which have numerous benefits over conventional treatments like surgery, chemotherapy, and radiation. Overall survival of cancer patients has improved significantly due to the use of immunotherapy. It acts as a novel pillar for treating different malignancies from their primary to the metastatic stage. Recent preferments in high-throughput sequencing and computational immunology leads to the development of targeted immunotherapy for precision oncology. In the last few decades, several computational methods and resources have been developed for designing immunotherapy against cancer. In this review, we have summarized cancer-associated genomic, transcriptomic, and mutation profile repositories. We have also enlisted in silico methods for the prediction of vaccine candidates, HLA binders, cytokines inducing peptides, and potential neoepitopes. Of note, we have incorporated the most important bioinformatics pipelines and resources for the designing of cancer immunotherapy. Moreover, to facilitate the scientific community, we have developed a web portal entitled ImmCancer (https://webs.iiitd.edu.in/raghava/immcancer/), comprises cancer immunotherapy tools and repositories.


Assuntos
Neoplasias , Biologia Computacional , Bases de Dados Factuais , Humanos , Imunoterapia/métodos , Medicina de Precisão
6.
Environ Sci Pollut Res Int ; 29(57): 86156-86179, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34655383

RESUMO

The exponential rise in the production of plastic and the consequential surge in plastic waste have led the scientists and researchers look out for innovative and sustainable means to reuse/recycle the plastic waste in order to reduce its negative impact on environment. Construction material, converting waste plastic into fuel, household goods, fabric and clothing are some of the sectors where waste plastic is emerging as a viable option. Out of these, construction material modified with plastic waste has garnered lot of attention. Modification of construction material with plastic waste serves a dual purpose. It reduces the amount of plastic waste going to landfills or litter and secondly lessens the use of mined construction materials, thereby mitigating the negative impact of construction industry on environment. This paper summarizes the developments with regard to the use of plastic waste as a constituent of construction material. Inclusion of plastic waste as a binder, aggregate, fine aggregate, modifier or substitute of cement and sand in the manufacturing of bricks, tiles, concrete and roads has been comprehensively reviewed. Also, the influence of addition of plastic waste on strength properties, water absorption, durability, etc. has been thoroughly discussed. The research studies considered for this review have been categorized based on whether they dealt with the use of plastic waste for bricks and tiles or in concrete for road construction.


Assuntos
Indústria da Construção , Gerenciamento de Resíduos , Plásticos , Reciclagem , Materiais de Construção , Resíduos Industriais/análise
7.
Proteomics ; 22(3): e2000311, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34637591

RESUMO

Numerous cancer-specific prognostic models have been developed in the past, wherein one model is applicable for only one type of cancer. In this study, an attempt has been made to identify universal or multi-cancer prognostic biomarkers and develop models for predicting survival risk across different types of cancer patients. In order to accomplish this, we gauged the prognostic role of mRNA expression of 165 apoptosis-related genes across 33 cancers in the context of patient survival. Firstly, we identified specific prognostic biomarker genes for 30 cancers. The cancer-specific prognostic models achieved a minimum Hazard Ratio, HRSKCM = 1.99 and maximum HRTHCA = 41.59. Secondly, a comprehensive analysis was performed to identify universal biomarkers across many cancers. Our best prognostic model consisted of 11 genes (TOP2A, ISG20, CD44, LEF1, CASP2, PSEN1, PTK2, SATB1, SLC20A1, EREG, and CD2) and stratified risk groups across 27 cancers (HROV = 1.53-HRUVM = 11.74). The model was validated on eight independent cancer cohorts and exhibited a comparable performance. Further, we clustered cancer-types on the basis of shared survival related apoptosis genes. This approach proved helpful in development of cross-cancer prognostic models. To show its efficacy, a prognostic model consisting of 15 genes was thereby developed for LGG-KIRC pair (HRKIRC = 3.27, HRLGG = 4.23). Additionally, we predicted potential therapeutic candidates for LGG-KIRC high risk patients.


Assuntos
Apoptose/genética , Neoplasias , Biomarcadores Tumorais/genética , Humanos , Neoplasias/genética , Prognóstico , Fatores de Risco , Análise de Sobrevida , Transcriptoma
8.
Front Pharmacol ; 13: 1035769, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36618941

RESUMO

Multifunctional nanoparticles are being formulated to overcome the side effects associated with anticancer drugs as well as conventional drug delivery systems. Cancer therapy has gained the advancement due to various pragmatic approaches with better treatment outcomes. The metal nanostructures such as gold and silver nanoparticles accessible via eco-friendly method provide amazing characteristics in the field of diagnosis and therapy towards cancer diseases. The environmental friendly approach has been proposed as a substitute to minimize the use of hazardous compounds associated in chemical synthesis of nanoparticles. In this attempt, researchers have used various microbes, and plant-based agents as reducing agents. In the last 2 decades various papers have been published emphasizing the benefits of the eco-friendly approach and advantages over the traditional method in the cancer therapy. Despite of various reports and published research papers, eco-based nanoparticles do not seem to find a way to clinical translation for cancer treatment. Present review enumerates the bibliometric data on biogenic silver and gold nanoparticles from Clarivate Analytics Web of Science (WoS) and Scopus for the duration 2010 to 2022 for cancer treatment with a special emphasis on breast, ovarian and cervical cancer. Furthermore, this review covers the recent advances in this area of research and also highlights the obstacles in the journey of biogenic nanodrug from clinic to market.

9.
Front Immunol ; 12: 780610, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34880873

RESUMO

Defensins are host defense peptides present in nearly all living species, which play a crucial role in innate immunity. These peptides provide protection to the host, either by killing microbes directly or indirectly by activating the immune system. In the era of antibiotic resistance, there is a need to develop a fast and accurate method for predicting defensins. In this study, a systematic attempt has been made to develop models for predicting defensins from available information on defensins. We created a dataset of defensins and non-defensins called the main dataset that contains 1,036 defensins and 1,035 AMPs (antimicrobial peptides, or non-defensins) to understand the difference between defensins and AMPs. Our analysis indicates that certain residues like Cys, Arg, and Tyr are more abundant in defensins in comparison to AMPs. We developed machine learning technique-based models on the main dataset using a wide range of peptide features. Our SVM (support vector machine)-based model discriminates defensins and AMPs with MCC of 0.88 and AUC of 0.98 on the validation set of the main dataset. In addition, we created an alternate dataset that consists of 1,036 defensins and 1,054 non-defensins obtained from Swiss-Prot. Models were also developed on the alternate dataset to predict defensins. Our SVM-based model achieved maximum MCC of 0.96 with AUC of 0.99 on the validation set of the alternate dataset. All models were trained, tested, and validated using standard protocols. Finally, we developed a web-based service "DefPred" to predict defensins, scan defensins in proteins, and design the best defensins from their analogs. The stand-alone software and web server of DefPred are available at https://webs.iiitd.edu.in/raghava/defpred.


Assuntos
Bases de Dados de Proteínas , Defensinas/análise , Software , Máquina de Vetores de Suporte , Animais , Humanos
10.
PLoS One ; 16(11): e0259534, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34767591

RESUMO

Aberrant expressions of apoptotic genes have been associated with papillary thyroid carcinoma (PTC) in the past, however, their prognostic role and utility as biomarkers remains poorly understood. In this study, we analysed 505 PTC patients by employing Cox-PH regression techniques, prognostic index models and machine learning methods to elucidate the relationship between overall survival (OS) of PTC patients and 165 apoptosis related genes. It was observed that nine genes (ANXA1, TGFBR3, CLU, PSEN1, TNFRSF12A, GPX4, TIMP3, LEF1, BNIP3L) showed significant association with OS of PTC patients. Five out of nine genes were found to be positively correlated with OS of the patients, while the remaining four genes were negatively correlated. These genes were used for developing risk prediction models, which can be utilized to classify patients with a higher risk of death from the patients which have a good prognosis. Our voting-based model achieved highest performance (HR = 41.59, p = 3.36x10-4, C = 0.84, logrank-p = 3.8x10-8). The performance of voting-based model improved significantly when we used the age of patients with prognostic biomarker genes and achieved HR = 57.04 with p = 10-4 (C = 0.88, logrank-p = 1.44x10-9). We also developed classification models that can classify high risk patients (survival ≤ 6 years) and low risk patients (survival > 6 years). Our best model achieved AUROC of 0.92. Further, the expression pattern of the prognostic genes was verified at mRNA level, which showed their differential expression between normal and PTC samples. Also, the immunostaining results from HPA validated these findings. Since these genes can also be used as potential therapeutic targets in PTC, we also identified potential drug molecules which could modulate their expression profile. The study briefly revealed the key prognostic biomarker genes in the apoptotic pathway whose altered expression is associated with PTC progression and aggressiveness. In addition to this, risk assessment models proposed here can help in efficient management of PTC patients.


Assuntos
Biomarcadores Tumorais , Aprendizado de Máquina , Câncer Papilífero da Tireoide , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Estudos de Coortes , Testes Diagnósticos de Rotina , Humanos , Prognóstico , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/metabolismo
11.
Brain Struct Funct ; 226(8): 2489-2495, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34269889

RESUMO

The blood-brain barrier poses major hurdles in the treatment of brain-related ailments. Over the past decade, interest in peptides-based therapeutics has thrived a lot because of their higher benefit to risk ratio. However, a complete knowledgebase providing a well-annotated picture of the peptide as a therapeutic molecule to cure brain-related ailments is lacking. We have built up a knowledgebase B3Pdb on blood-brain barrier (BBB)-penetrating peptides in the present study. The B3Pdb holds clinically relevant experimental information on 1225 BBB-penetrating peptides, including mode of delivery, animal model, in vitro/in vivo experiments, chemical modifications, length. Hoping that drug delivery systems can improve central nervous system disorder-related therapeutics. In this regard, B3Pdb is an important resource to support the rational design of therapeutics peptides for CNS-related disorders. The complete ready-to-use and updated database with a user-friendly web interface is available to the scientific community at https://webs.iiitd.edu.in/raghava/b3pdb/ .


Assuntos
Barreira Hematoencefálica , Doenças do Sistema Nervoso Central , Animais , Encéfalo , Sistemas de Liberação de Medicamentos , Peptídeos
12.
Mol Diagn Ther ; 25(5): 629-646, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34155607

RESUMO

INTRODUCTION: Uterine corpus endometrial carcinoma (UCEC) causes thousands of deaths per year. To improve the overall survival of patients with UCEC, there is a need to identify prognostic biomarkers and potential drugs. OBJECTIVES: The aim of this study was twofold: the identification of prognostic gene signatures from expression profiles of pattern recognition receptor (PRR) genes and identification of the most effective existing drugs using the prognostic gene signature. METHODS: This study was based on the expression profile of PRR genes of 541 patients with UCEC obtained from The Cancer Genome Atlas. Key prognostic signatures were identified using various approaches, including survival analysis, network, and clustering. Hub genes were identified by constructing a co-expression network. Representative genes were identified using k-means and k-medoids-based clustering. Univariate Cox proportional hazard (PH) analysis was used to identify survival-associated genes. 'cmap2' was used to identify potential drugs that can suppress/enhance the expression of prognostic genes. RESULTS: Models were developed using hub genes and achieved a maximum hazard ratio (HR) of 1.37 (p = 0.294). Then, a clustering-based model was developed using seven genes (HR 9.14; p = 1.49 × 10-12). Finally, a nine gene-based risk stratification model was developed (CLEC1B, CLEC3A, IRF7, CTSB, FCN1, RIPK2, NLRP10, NLRP9, and SARM1) and achieved HR 10.70; p = 1.1 × 10-12. The performance of this model improved significantly in combination with the clinical stage and achieved HR 15.23; p = 2.21 × 10-7. We also developed a model for predicting high-risk patients (survival ≤ 4.3 years) and achieved an area under the receiver operating characteristic curve (AUROC) of 0.86. CONCLUSION: We identified potential immunotherapeutic agents based on prognostic gene signature: hexamethonium bromide and isoflupredone. Several novel candidate drugs were suggested, including human interferon-α-2b, paclitaxel, imiquimod, MESO-DAP1, and mifamurtide. These biomolecules and repurposed drugs may be utilised for prognosis and treatment for better survival.


Assuntos
Neoplasias do Endométrio , Preparações Farmacêuticas , Biomarcadores Tumorais/genética , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Lectinas Tipo C , Prognóstico
13.
Monoclon Antib Immunodiagn Immunother ; 39(6): 204-216, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33136473

RESUMO

A web-based resource CoronaVIR (https://webs.iiitd.edu.in/raghava/coronavir/) has been developed to maintain the predicted and existing information on coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We have integrated multiple modules, including "Genomics," "Diagnosis," "Immunotherapy," and "Drug Designing" to understand the holistic view of this pandemic medical disaster. The genomics module provides genomic information of different strains of this virus to understand genomic level alterations. The diagnosis module includes detailed information on currently-in-use diagnostics tests as well as five novel universal primer sets predicted using in silico tools. The Immunotherapy module provides information on epitope-based potential vaccine candidates (e.g., LQLPQGTTLPKGFYA, VILLNKHIDAYKTFPPTEPKKDKKKK, EITVATSRTLS, GKGQQQQGQTV, SELVIGAVILR) predicted using state-of-the-art software and resources in the field of immune informatics. These epitopes have the potential to activate both adaptive (e.g., B cell and T cell) and innate (e.g., vaccine adjuvants) immune systems as well as suitable for all strains of SARS-CoV-2. Besides, we have also predicted potential candidates for siRNA-based therapy and RNA-based vaccine adjuvants. The drug designing module maintains information about potential drug targets, tertiary structures, and potential drug molecules. These potential drug molecules were identified from FDA-approved drugs using the docking-based approach. We also compiled information from the literature and Internet on potential drugs, repurposing drugs, and monoclonal antibodies. To understand host-virus interaction, we identified cell-penetrating peptides in the virus. In this study, state-of-the-art techniques have been used for predicting the potential candidates for diagnostics and therapeutics.


Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , Bases de Dados Factuais , Centros de Informação , Internet , Antivirais/farmacologia , COVID-19/diagnóstico , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Desenho de Fármacos , Humanos , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/imunologia
14.
Heliyon ; 6(8): e04811, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32913910

RESUMO

Risk assessment in cutaneous melanoma (CM) patients is one of the major challenges in the effective treatment of CM patients. Traditionally, clinico-pathological features such as Breslow thickness, American Joint Committee on Cancer (AJCC) tumor staging, etc. are utilized for this purpose. However, due to advancements in technology, most of the upcoming risk prediction methods are gene-expression profile (GEP) based. In this study, we have tried to develop new GEP and clinico-pathological features-based biomarkers and assessed their prognostic strength in contrast to existing prognostic methods. We developed risk prediction models using the expression of the genes associated with different cancer-related pathways and got a maximum hazard ratio (HR) of 2.52 with p-value ~10-8 for the apoptotic pathway. Another model, based on combination of apoptotic and notch pathway genes boosted the HR to 2.57. Next, we developed models based on individual clinical features and got a maximum HR of 2.45 with p-value ~10-6 for Breslow thickness. We also developed models using the best features of clinical as well as gene-expression data and obtained a maximum HR of 3.19 with p-value ~10-9. Finally, we developed a new ensemble method using clinical variables only and got a maximum HR of 6.40 with p-value ~10-15. Based on this method, a web-based service and an android application named 'CMcrpred' is available at (https://webs.iiitd.edu.in/raghava/cmcrpred/) and Google Play Store respectively to facilitate scientific community. This study reveals that our new ensemble method based on only clinico-pathological features overperforms methods based on GEP based profiles as well as currently used AJCC staging. It also highlights the need to explore the full potential of clinical variables for prognostication of cancer patients.

15.
Database (Oxford) ; 20202020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32147717

RESUMO

Liver cancer is the fourth major lethal malignancy worldwide. To understand the development and progression of liver cancer, biomedical research generated a tremendous amount of transcriptomics and disease-specific biomarker data. However, dispersed information poses pragmatic hurdles to delineate the significant markers for the disease. Hence, a dedicated resource for liver cancer is required that integrates scattered multiple formatted datasets and information regarding disease-specific biomarkers. Liver Cancer Expression Resource (CancerLivER) is a database that maintains gene expression datasets of liver cancer along with the putative biomarkers defined for the same in the literature. It manages 115 datasets that include gene-expression profiles of 9611 samples. Each of incorporated datasets was manually curated to remove any artefact; subsequently, a standard and uniform pipeline according to the specific technique is employed for their processing. Additionally, it contains comprehensive information on 594 liver cancer biomarkers which include mainly 315 gene biomarkers or signatures and 178 protein- and 46 miRNA-based biomarkers. To explore the full potential of data on liver cancer, a web-based interactive platform was developed to perform search, browsing and analyses. Analysis tools were also integrated to explore and visualize the expression patterns of desired genes among different types of samples based on individual gene, GO ontology and pathways. Furthermore, a dataset matrix download facility was provided to facilitate the users for their extensive analysis to elucidate more robust disease-specific signatures. Eventually, CancerLivER is a comprehensive resource which is highly useful for the scientific community working in the field of liver cancer.Availability: CancerLivER can be accessed on the web at https://webs.iiitd.edu.in/raghava/cancerliver.


Assuntos
Biomarcadores Tumorais/genética , Biologia Computacional/métodos , Bases de Dados Genéticas , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , Curadoria de Dados/métodos , Mineração de Dados/métodos , Ontologia Genética , Humanos , Internet
16.
Front Immunol ; 11: 71, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32082326

RESUMO

This study describes a method developed for predicting pattern recognition receptors (PRRs), which are an integral part of the immune system. The models developed here were trained and evaluated on the largest possible non-redundant PRRs, obtained from PRRDB 2.0, and non-pattern recognition receptors (Non-PRRs), obtained from Swiss-Prot. Firstly, a similarity-based approach using BLAST was used to predict PRRs and got limited success due to a large number of no-hits. Secondly, machine learning-based models were developed using sequence composition and achieved a maximum MCC of 0.63. In addition to this, models were developed using evolutionary information in the form of PSSM composition and achieved maximum MCC value of 0.66. Finally, we developed hybrid models that combined a similarity-based approach using BLAST and machine learning-based models. Our best model, which combined BLAST and PSSM based model, achieved a maximum MCC value of 0.82 with an AUROC value of 0.95, utilizing the potential of both similarity-based search and machine learning techniques. In order to facilitate the scientific community, we also developed a web server "PRRpred" based on the best model developed in this study (http://webs.iiitd.edu.in/raghava/prrpred/).


Assuntos
Modelos Biológicos , Receptores de Reconhecimento de Padrão/imunologia , Sequência de Aminoácidos , Bases de Dados de Proteínas , Aprendizado de Máquina , Análise de Sequência de Proteína
17.
Database (Oxford) ; 20192019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31250014

RESUMO

PRRDB 2.0 is an updated version of PRRDB that maintains comprehensive information about pattern-recognition receptors (PRRs) and their ligands. The current version of the database has ~2700 entries, which are nearly five times of the previous version. It contains extensive information about 467 unique PRRs and 827 pathogens-associated molecular patterns (PAMPs), manually extracted from ~600 research articles. It possesses information about PRRs and PAMPs that has been extracted manually from research articles and public databases. Each entry provides comprehensive details about PRRs and PAMPs that includes their name, sequence, origin, source, type, etc. We have provided internal and external links to various databases/resources (like Swiss-Prot, PubChem) to obtain further information about PRRs and their ligands. This database also provides links to ~4500 experimentally determined structures in the protein data bank of various PRRs and their complexes. In addition, 110 PRRs with unknown structures have also been predicted, which are important in order to understand the structure-function relationship between receptors and their ligands. Numerous web-based tools have been integrated into PRRDB 2.0 to facilitate users to perform different tasks like (i) extensive searching of the database; (ii) browsing or categorization of data based on receptors, ligands, source, etc. and (iii) similarity search using BLAST and Smith-Waterman algorithm.


Assuntos
Algoritmos , Bases de Dados de Proteínas , Ligantes , Receptores de Reconhecimento de Padrão , Software , Animais , Gerenciamento de Dados , Humanos
18.
J Phys Chem B ; 113(16): 5381-90, 2009 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-19323513

RESUMO

Room temperature ionic liquid 2,3-dimethyl-1-hexylimidazolium bis(trifluoromethane sulfonyl)imide (DMHxImTFSI) has been synthesized and used in the preparation of polymer gel electrolytes containing polymethylmethacrylate and propylene carbonate (PC). The onset of ion diffusional motion has been studied by (1)H and (19)F NMR spectroscopy and the results obtained for ionic liquid, liquid electrolytes, and polymer gel electrolytes have been correlated with the ionic conductivity results for these electrolytes in the 100-400 K temperature range. The temperature at which (1)H and (19)F NMR lines show motional narrowing and hence ion diffusional motion starts has been found to be closely related to the temperature at which a large increase in ionic conductivity has been observed for these electrolytes. Polymer gel electrolytes have high ionic conductivity over a wide range of temperatures. Thermogravimetric analysis/differential scanning calorimetry studies show that the ionic liquid (DMHxImTFSI) used in the present study is thermally stable up to 400 degrees C, whereas the addition of PC lowers the thermal stability of polymer gel electrolytes containing the ionic liquid. Different electrolytes have been observed to show high ionic conductivity in different range of temperatures, which can be helpful in the design of polymer gel electrolytes for specific applications.


Assuntos
Eletrólitos/química , Imidazóis/química , Líquidos Iônicos/química , Difusão , Condutividade Elétrica , Géis/química , Imidazóis/síntese química , Líquidos Iônicos/síntese química , Polimetil Metacrilato/química , Propano/análogos & derivados , Propano/química , Temperatura
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