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  1. Article ; Online: QPromoters

    Devang Haresh Liya / Mirudula Elanchezhian / Mukulika Pahari / Nithishwer Mouroug Anand / Shivani Suresh / Nivedha Balaji / Ashwin Kumar Jainarayanan

    All Life, Vol 16, Iss

    sequence based prediction of promoter strength in Saccharomyces cerevisiae

    2023  Volume 1

    Abstract: Promoters play a key role in influencing transcriptional regulation for fine-tuning the expression of genes. Heterologous promoter engineering has been a widely used concept to control the level of transcription in all model organisms. The strength of a ... ...

    Abstract Promoters play a key role in influencing transcriptional regulation for fine-tuning the expression of genes. Heterologous promoter engineering has been a widely used concept to control the level of transcription in all model organisms. The strength of a promoter is mainly determined by its nucleotide composition. Many promoter libraries have been curated, but few have attempted to develop theoretical methods to predict the strength of promoters from their nucleotide sequence. Such theoretical methods are not only valuable in the design of promoters with specified strength but are also meaningful in understanding the mechanistic role of promoters in transcriptional regulation. In this study, we present a theoretical model to describe the relationship between promoter strength and nucleotide sequence in Saccharomyces cerevisiae. We infer from our analysis that the −49–10 sequence with respect to the Transcription Start Site represents the minimal region that can be used to predict promoter strength. https://qpromoters.com/ and a standalone tool https://github.com/DevangLiya/QPromoters to quickly quantify the strength of Saccharomyces cerevisiae promoters.
    Keywords computational life sciences ; bioinformatics and system biology ; Biotechnology ; TP248.13-248.65 ; Life ; QH501-531
    Subject code 570
    Language English
    Publishing date 2023-12-01T00:00:00Z
    Publisher Taylor & Francis Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Pseudotime dynamics of T cells in pancreatic ductal adenocarcinoma inform distinct functional states within the regulatory and cytotoxic T cells.

    Jainarayanan, Ashwin / Mouroug-Anand, Nithishwer / Arbe-Barnes, Edward H / Bush, Adam J / Bashford-Rogers, Rachael / Frampton, Adam / Heij, Lara / Middleton, Mark / Dustin, Michael L / Abu-Shah, Enas / Sivakumar, Shivan

    iScience

    2023  Volume 26, Issue 4, Page(s) 106324

    Abstract: Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest types of cancer and has a 5-year survival of less than 8% owing to its complex biology. As PDAC is refractory to immunotherapy, we need to understand the functional dynamics of T cells in the ...

    Abstract Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest types of cancer and has a 5-year survival of less than 8% owing to its complex biology. As PDAC is refractory to immunotherapy, we need to understand the functional dynamics of T cells in the PDAC microenvironment to develop alternative therapeutic strategies. In this study, we performed RNA velocity-based pseudotime analysis on a scRNA-seq dataset from surgically resected human PDAC specimens to gain insight into temporal gene expression patterns that best characterize the cell fates. The tumor microenvironment was seen to encompass a range of terminal states for the T cell trajectories with suppressive and non-tumor-responsive T cells dominating them. However, the results also reveal the existence of a functional branch of the T cell population that was not transitioning to exhausted and senescent states. These findings reveal various microenvironmental signals driving T cell patterns which can be useful in identifying new therapeutic avenues.
    Language English
    Publishing date 2023-03-07
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2023.106324
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Analysing non-synonymous mutations in XDR and MDR tuberculosis drugs.

    Surana, Pallavi / Jainarayanan, Ashwin Kumar / Anand, Nithishwer Mouroug / Sharma, Mukta

    Journal of clinical tuberculosis and other mycobacterial diseases

    2019  Volume 17, Page(s) 100124

    Abstract: Tuberculosis is a bacterial disease caused ... ...

    Abstract Tuberculosis is a bacterial disease caused by
    Language English
    Publishing date 2019-09-19
    Publishing country England
    Document type Journal Article
    ISSN 2405-5794
    ISSN (online) 2405-5794
    DOI 10.1016/j.jctube.2019.100124
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Drug repurposing and sequence analysis in S-glycoprotein variants reveals critical signature patterns and destabilization of receptor-binding domain in omicron variant.

    Liya, Devang Haresh / Anand, Nithishwer Mouroug / Jainarayanan, Ashwin Kumar / Elanchezhian, Mirudula / Seetharaman, Madhumati / Balakannan, Dhanuush / Pradhan, Arpit Kumar

    Journal of biomolecular structure & dynamics

    2022  Volume 41, Issue 16, Page(s) 7931–7948

    Abstract: The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus since its emergence in 2019 has yielded several new viral variants with varied infectivity, disease severity, and antigenicity. Although most mutations are expected ... ...

    Abstract The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus since its emergence in 2019 has yielded several new viral variants with varied infectivity, disease severity, and antigenicity. Although most mutations are expected to be relatively neutral, mutations at the Spike region of the genome have shown to have a major impact on the viral transmission and infection in humans. Therefore, it is crucial to survey the structures of spike protein across the global virus population to contextualize the rate of therapeutic success against these variants. In this study, high-frequency mutational variants from different geographic regions were pooled in order to study the structural evolution of the spike protein through drug docking and MD simulations. We investigated the mutational burden in the spike subregions and have observed that the different variants harbour unique signature patterns in the spike subregions, with certain domains being highly prone to mutations. Further, the MD simulations and docking study revealed that different variants show differential stability when docked for the same set of drug targets. This work sheds light on the mutational burden and the stability landscape of the spike protein across the variants from different geographical regions.Communicated by Ramaswamy H. Sarma.
    Language English
    Publishing date 2022-09-29
    Publishing country England
    Document type Journal Article
    ZDB-ID 49157-3
    ISSN 1538-0254 ; 0739-1102
    ISSN (online) 1538-0254
    ISSN 0739-1102
    DOI 10.1080/07391102.2022.2127902
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Pseudotime dynamics of T cells in pancreatic ductal adenocarcinoma inform distinct functional states within the regulatory and cytotoxic T cells

    Ashwin Jainarayanan / Nithishwer Mouroug-Anand / Edward H. Arbe-Barnes / Adam J. Bush / Rachael Bashford-Rogers / Adam Frampton / Lara Heij / Mark Middleton / Michael L. Dustin / Enas Abu-Shah / Shivan Sivakumar

    iScience, Vol 26, Iss 4, Pp 106324- (2023)

    2023  

    Abstract: Summary: Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest types of cancer and has a 5-year survival of less than 8% owing to its complex biology. As PDAC is refractory to immunotherapy, we need to understand the functional dynamics of T ... ...

    Abstract Summary: Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest types of cancer and has a 5-year survival of less than 8% owing to its complex biology. As PDAC is refractory to immunotherapy, we need to understand the functional dynamics of T cells in the PDAC microenvironment to develop alternative therapeutic strategies. In this study, we performed RNA velocity-based pseudotime analysis on a scRNA-seq dataset from surgically resected human PDAC specimens to gain insight into temporal gene expression patterns that best characterize the cell fates. The tumor microenvironment was seen to encompass a range of terminal states for the T cell trajectories with suppressive and non-tumor-responsive T cells dominating them. However, the results also reveal the existence of a functional branch of the T cell population that was not transitioning to exhausted and senescent states. These findings reveal various microenvironmental signals driving T cell patterns which can be useful in identifying new therapeutic avenues.
    Keywords Immune response ; Bioinformatics ; Cancer systems biology ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2023-04-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: A comprehensive SARS-CoV-2 genomic analysis identifies potential targets for drug repurposing.

    Nithishwer Mouroug Anand / Devang Haresh Liya / Arpit Kumar Pradhan / Nitish Tayal / Abhinav Bansal / Sainitin Donakonda / Ashwin Kumar Jainarayanan

    PLoS ONE, Vol 16, Iss 3, p e

    2021  Volume 0248553

    Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is a novel human coronavirus strain (HCoV) was initially reported in December 2019 in Wuhan City, China. This acute infection caused pneumonia-like symptoms and other respiratory ... ...

    Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is a novel human coronavirus strain (HCoV) was initially reported in December 2019 in Wuhan City, China. This acute infection caused pneumonia-like symptoms and other respiratory tract illness. Its higher transmission and infection rate has successfully enabled it to have a global spread over a matter of small time. One of the major concerns involving the SARS-COV-2 is the mutation rate, which enhances the virus evolution and genome variability, thereby making the design of therapeutics difficult. In this study, we identified the most common haplotypes from the haplotype network. The conserved genes and population level variants were analysed. Non-Structural Protein 10 (NSP10), Nucleoprotein, Papain-like protease (Plpro or NSP3) and 3-Chymotrypsin like protease (3CLpro or NSP5), which were conserved at the highest threshold, were used as drug targets for molecular dynamics simulations. Darifenacin, Nebivolol, Bictegravir, Alvimopan and Irbesartan are among the potential drugs, which are suggested for further pre-clinical and clinical trials. This particular study provides a comprehensive targeting of the conserved genes. We also identified the mutation frequencies across the viral genome.
    Keywords Medicine ; R ; Science ; Q
    Subject code 572
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: A comprehensive SARS-CoV-2 genomic analysis identifies potential targets for drug repurposing.

    Anand, Nithishwer Mouroug / Liya, Devang Haresh / Pradhan, Arpit Kumar / Tayal, Nitish / Bansal, Abhinav / Donakonda, Sainitin / Jainarayanan, Ashwin Kumar

    PloS one

    2021  Volume 16, Issue 3, Page(s) e0248553

    Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is a novel human coronavirus strain (HCoV) was initially reported in December 2019 in Wuhan City, China. This acute infection caused pneumonia-like symptoms and other respiratory ... ...

    Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is a novel human coronavirus strain (HCoV) was initially reported in December 2019 in Wuhan City, China. This acute infection caused pneumonia-like symptoms and other respiratory tract illness. Its higher transmission and infection rate has successfully enabled it to have a global spread over a matter of small time. One of the major concerns involving the SARS-COV-2 is the mutation rate, which enhances the virus evolution and genome variability, thereby making the design of therapeutics difficult. In this study, we identified the most common haplotypes from the haplotype network. The conserved genes and population level variants were analysed. Non-Structural Protein 10 (NSP10), Nucleoprotein, Papain-like protease (Plpro or NSP3) and 3-Chymotrypsin like protease (3CLpro or NSP5), which were conserved at the highest threshold, were used as drug targets for molecular dynamics simulations. Darifenacin, Nebivolol, Bictegravir, Alvimopan and Irbesartan are among the potential drugs, which are suggested for further pre-clinical and clinical trials. This particular study provides a comprehensive targeting of the conserved genes. We also identified the mutation frequencies across the viral genome.
    MeSH term(s) COVID-19/virology ; Drug Discovery/methods ; Drug Repositioning/methods ; Genome, Viral ; Humans ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Mutation Rate ; SARS-CoV-2/drug effects ; SARS-CoV-2/genetics ; SARS-CoV-2/metabolism ; Viral Proteins/genetics ; Viral Proteins/metabolism ; COVID-19 Drug Treatment
    Chemical Substances Viral Proteins
    Language English
    Publishing date 2021-03-18
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0248553
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Book ; Online: A Comprehensive SARS-CoV-2 Genomic Analysis Identifies Potential Targets for Drug Repurposing

    Nithishwer Mouroug Anand / Devang Haresh Liya / Arpit Kumar Pradhan / Nitish Tayal / Abhinav Bansal / Sainitin Donakonda / Ashwin Kumar Jainarayanan

    2020  

    Abstract: Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is a novel human coronavirus strain (HCoV) initially reported in December 2019 in Wuhan City, China causing pneumonia-like symptoms and other respiratory tract illness. It’ ...

    Abstract Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is a novel human coronavirus strain (HCoV) initially reported in December 2019 in Wuhan City, China causing pneumonia-like symptoms and other respiratory tract illness. It’s higher transmission and infection rate has successfully enabled it to have a global spread over a matter of small time. With 6,529,240 cases and about 385,264 deaths, this pandemic has become a global concern with certain drugs and vaccines failing at later clinical trials. Materials and Methods: Phylogenetic Analysis, Haplotype Network, Analysis of conserved genes and population-level variants, Using conserved genes as targets for drug designing, Docking studies and Molecular Dynamics (MD) simulations to predict the stability of Drug-Ligand Complex. Results: We identified the most common haplotypes from the haplotype network and at least seven different clusters were found signifying seven different viral lineages across the globe. We studied the mutation frequency across the SARS-CoV-2 viral genome. The conserved genes and population level variants were analyzed and NSP10, Nucleoprotein, Plpro and 3CLpro which were conserved at the highest threshold were used as drug targets for molecular dynamics simulations. Darifenacin, Nebivolol, Bictegravir, Alvimopan and Irbesartan are among the potential drugs which are suggested for further pre-clinical and clinical trials. Significance: This particular study provides a comprehensive targeting of the conserved genes as a novel approach for drug targeting. The conserved gene approach could also be of a big use while designing vaccines and cure. Mutations in the viral genome make the designing of the drugs a challenging task which has a higher risk of failure at later clinical trials. This approach of targeting the stable genes for drug discovery would provide a better therapeutic approach and confidence in the successive clinical trials. We also identified the global level spread of SARS-CoV-2 and mutation frequencies across the viral genome. Our study gives insights of the origin and global spread of the SARS-CoV-2. The data provided in this study can further be used by other groups to understand and combat Covid 19.
    Keywords Bioinformatics and Computational Biology ; COVID 19 ; coronavirus ; SARS-CoV-2 ; SARS-CoV ; Haplotype network ; Phylogenetic Analysis ; MD simulation ; Drug-Ligand interactions ; Mutation Frequency ; Docking ; Population level variants ; covid19
    Subject code 572
    Publishing date 2020-06-05T13:22:23Z
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Book ; Online: A Comprehensive SARS-CoV-2 Genomic Analysis Identifies Potential Targets for Drug Repurposing

    Mouroug Anand, Nithishwer / Haresh Liya, Devang / Pradhan, Arpit Kumar / Tayal, Nitish / Bansal, Abhinav / Donakonda, Sainitin / Jainarayanan, Ashwin Kumar

    2020  

    Abstract: ... Background: ... The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is a novel human coronavirus strain (HCoV) initially reported in December 2019 in Wuhan City, China causing pneumonia-like symptoms and other respiratory tract ... ...

    Abstract

    Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is a novel human coronavirus strain (HCoV) initially reported in December 2019 in Wuhan City, China causing pneumonia-like symptoms and other respiratory tract illness. It’s higher transmission and infection rate has successfully enabled it to have a global spread over a matter of small time. With 6,529,240 cases and about 385,264 deaths, this pandemic has become a global concern with certain drugs and vaccines failing at later clinical trials.

    Materials and Methods: Phylogenetic Analysis, Haplotype Network, Analysis of conserved genes and population-level variants, Using conserved genes as targets for drug designing, Docking studies and Molecular Dynamics (MD) simulations to predict the stability of Drug-Ligand Complex.

    Results: We identified the most common haplotypes from the haplotype network and at least seven different clusters were found signifying seven different viral lineages across the globe. We studied the mutation frequency across the SARS-CoV-2 viral genome. The conserved genes and population level variants were analyzed and NSP10, Nucleoprotein, Plpro and 3CLpro which were conserved at the highest threshold were used as drug targets for molecular dynamics simulations. Darifenacin, Nebivolol, Bictegravir, Alvimopan and Irbesartan are among the potential drugs which are suggested for further pre-clinical and clinical trials.

    Significance: This particular study provides a comprehensive targeting of the conserved genes as a novel approach for drug targeting. The conserved gene approach could also be of a big use while designing vaccines and cure. Mutations in the viral genome make the designing of the drugs a challenging task which has a higher risk of failure at later clinical trials. This approach of targeting the stable genes for drug discovery would provide a better therapeutic approach and confidence in the successive clinical trials. We also identified the global level spread of SARS-CoV-2 and mutation frequencies across the viral genome. Our study gives insights of the origin and global spread of the SARS-CoV-2. The data provided in this study can further be used by other groups to understand and combat Covid 19.


    Keywords covid19
    Publisher American Chemical Society (ACS)
    Publishing country us
    Document type Book ; Online
    DOI 10.26434/chemrxiv.12430919.v1
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Book ; Online: A Comprehensive SARS-CoV-2 Genomic Analysis Identifies Potential Targets for Drug Repurposing

    Mouroug Anand, Nithishwer / Haresh Liya, Devang / Pradhan, Arpit Kumar / Tayal, Nitish / Bansal, Abhinav / Donakonda, Sainitin / Jainarayanan, Ashwin Kumar

    2020  

    Abstract: ... Background: ... The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is a novel human coronavirus strain (HCoV) initially reported in December 2019 in Wuhan City, China causing pneumonia-like symptoms and other respiratory tract ... ...

    Abstract

    Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is a novel human coronavirus strain (HCoV) initially reported in December 2019 in Wuhan City, China causing pneumonia-like symptoms and other respiratory tract illness. It’s higher transmission and infection rate has successfully enabled it to have a global spread over a matter of small time. With 6,529,240 cases and about 385,264 deaths, this pandemic has become a global concern with certain drugs and vaccines failing at later clinical trials.

    Materials and Methods: Phylogenetic Analysis, Haplotype Network, Analysis of conserved genes and population-level variants, Using conserved genes as targets for drug designing, Docking studies and Molecular Dynamics (MD) simulations to predict the stability of Drug-Ligand Complex.

    Results: We identified the most common haplotypes from the haplotype network and at least seven different clusters were found signifying seven different viral lineages across the globe. We studied the mutation frequency across the SARS-CoV-2 viral genome. The conserved genes and population level variants were analyzed and NSP10, Nucleoprotein, Plpro and 3CLpro which were conserved at the highest threshold were used as drug targets for molecular dynamics simulations. Darifenacin, Nebivolol, Bictegravir, Alvimopan and Irbesartan are among the potential drugs which are suggested for further pre-clinical and clinical trials.

    Significance: This particular study provides a comprehensive targeting of the conserved genes as a novel approach for drug targeting. The conserved gene approach could also be of a big use while designing vaccines and cure. Mutations in the viral genome make the designing of the drugs a challenging task which has a higher risk of failure at later clinical trials. This approach of targeting the stable genes for drug discovery would provide a better therapeutic approach and confidence in the successive clinical trials. We also identified the global level spread of SARS-CoV-2 and mutation frequencies across the viral genome. Our study gives insights of the origin and global spread of the SARS-CoV-2. The data provided in this study can further be used by other groups to understand and combat Covid 19.


    Keywords covid19
    Publisher American Chemical Society (ACS)
    Publishing country us
    Document type Book ; Online
    DOI 10.26434/chemrxiv.12430919
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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