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PROVIDER: PRJEB64245 | ENA |
REPOSITORIES: ENA
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Project description:Pathogen genomic surveillance as a scalable framework for precision phage therapy - phage resistant genomes
| PRJEB64574 | ENA
Project description:Hospital-wide pathogen transmission surveillance combining epidemiological, genetic, and spectroscopic approaches
| PRJEB62643 | ENA
Project description:Bacteriophage (phage) therapy is a promising alternative to antibiotics, yet phage-induced immune responses can affect treatment efficacy. However, current methods for assessing phage immunogenicity are limited, hindering the development of safer, more effective therapies. Here, we introduce the Bacteriophage Risk Index (BRI), a novel metric that quantifies phage immunogenic potential based on CpG dinucleotide frequency, motif spacing, and sequence context, key factors influencing Toll-like receptor 9 (TLR9) activation. Applying the BRI to 7,011 phage genomes, we classified them into five risk tiers, revealing substantial immunogenic variability, even among phages targeting the same bacterial host. BRI scores correlated with immune responses in human lung epithelial cells, validating its predictive power. Experimental testing further confirmed this, as exposure of lung epithelial cells to two phages from distinct risk tiers showed that the high-risk phage (Category 4) induced a strong pro-inflammatory response, upregulating CXCL1, CXCL8, IRF7, and TNFAIP3, while the low-risk phage (Category 2) triggered minimal immune activation with limited cytokine expression. These findings confirm that higher BRI scores predict stronger immune responses, providing a robust tool for evaluating phage immunogenicity. By enabling the selection of phages with lower immunogenic potential, the BRI enhances the safety and efficacy of phage therapy while offering a standardized framework for regulatory agencies, clinical researchers, and biologic drug development, with applications extending beyond phage therapy to other immunogenic biologics.
2025-06-16 | GSE293045 | GEO
Project description:Single cell multi-omic readouts of both the cellular transcriptome and proteome have significantly enhanced our ability to comprehensively characterize cellular states. Most approaches in this area rely on oligonucleotide barcode-conjugated antibodies that target cell surface epitopes of interest, enabling their concomitant detection with the transcriptome. However, a similar high-throughput measurement of other cellular modalities such as the epigenome in concert with protein levels have not been described. Moreover, detection of epitopes is limited to antigens for which a specific antibody is available. Here, we introduce PHAGE-ATAC, an approach that enables the scalable and simultaneous detection of protein levels and chromatin accessibility data in single cells using the assay of transposase-accessible chromatin with sequencing (ATAC-seq). Quantitative detection of proteins by PHAGE-ATAC is accomplished through the use of engineerable nanobody-displaying phages that are genetically barcoded within the nanobody-encoding phagemids. We demonstrate the utility of PHAGE-ATAC for multimodal single cell genomic analysis in both cell lines and primary human cells. Analogous to phage display approaches, we further establish a synthetic high-complexity library of nanobody-displaying phages and demonstrate its utility to select novel antigen-specific nanobodies for PHAGE-ATAC.
2021-10-21 | GSE157485 | GEO
Project description:Single cell multi-omic readouts of both the cellular transcriptome and proteome have significantly enhanced our ability to comprehensively characterize cellular states. Most approaches in this area rely on oligonucleotide barcode-conjugated antibodies that target cell surface epitopes of interest, enabling their concomitant detection with the transcriptome. However, a similar high-throughput measurement of other cellular modalities such as the epigenome in concert with protein levels have not been described. Moreover, detection of epitopes is limited to antigens for which a specific antibody is available. Here, we introduce PHAGE-ATAC, an approach that enables the scalable and simultaneous detection of protein levels and chromatin accessibility data in single cells using the assay of transposase-accessible chromatin with sequencing (ATAC-seq). Quantitative detection of proteins by PHAGE-ATAC is accomplished through the use of engineerable nanobody-displaying phages that are genetically barcoded within the nanobody-encoding phagemids. We demonstrate the utility of PHAGE-ATAC for multimodal single cell genomic analysis in both cell lines and primary human cells. Analogous to phage display approaches, we further establish a synthetic high-complexity library of nanobody-displaying phages and demonstrate its utility to select novel antigen-specific nanobodies for PHAGE-ATAC.
2021-10-21 | GSE157483 | GEO
Project description:Single cell multi-omic readouts of both the cellular transcriptome and proteome have significantly enhanced our ability to comprehensively characterize cellular states. Most approaches in this area rely on oligonucleotide barcode-conjugated antibodies that target cell surface epitopes of interest, enabling their concomitant detection with the transcriptome. However, a similar high-throughput measurement of other cellular modalities such as the epigenome in concert with protein levels have not been described. Moreover, detection of epitopes is limited to antigens for which a specific antibody is available. Here, we introduce PHAGE-ATAC, an approach that enables the scalable and simultaneous detection of protein levels and chromatin accessibility data in single cells using the assay of transposase-accessible chromatin with sequencing (ATAC-seq). Quantitative detection of proteins by PHAGE-ATAC is accomplished through the use of engineerable nanobody-displaying phages that are genetically barcoded within the nanobody-encoding phagemids. We demonstrate the utility of PHAGE-ATAC for multimodal single cell genomic analysis in both cell lines and primary human cells. Analogous to phage display approaches, we further establish a synthetic high-complexity library of nanobody-displaying phages and demonstrate its utility to select novel antigen-specific nanobodies for PHAGE-ATAC.
2021-10-21 | GSE157478 | GEO
Project description:Bacteriophages (hereafter “phages”) are ubiquitous predators of bacteria in the natural world, but interest is growing in their development into antibacterial therapy as complement or replacement for antibiotics. However, bacteria have evolved a huge variety of anti-phage defense systems allowing them to resist phage lysis to a greater or lesser extent, and in pathogenic bacteria these inevitably impact phage therapy outcomes. In addition to dedicated phage defense systems, some aspects of the general stress response also impact phage susceptibility, but the details of this are not well known. In order to elucidate these factors in the opportunistic pathogen Pseudomonas aeruginosa, we used the laboratory-conditioned strain PAO1 as host for phage infection experiments as it is naturally poor in dedicated phage defense systems. Screening by transposon insertion sequencing indicated that the uncharacterized operon PA3040-PA3042 was potentially associated with resistance to lytic phages. However, we found that its primary role appeared to be in regulating biofilm formation. Its expression was highly growth-phase dependent and responsive to phage infection and cell envelope stress.
2023-10-30 | GSE246284 | GEO
Project description:Antibiotic use can lead to expansion of multi-drug resistant pathobionts within the gut microbiome that can cause life-threatening infections. Selective alternatives to conventional antibiotics are in dire need. Here, we describe a Klebsiella PhageBank that enables the rapid design of antimicrobial bacteriophage cocktails to treat multi-drug resistant Klebsiella pneumoniae. Using a transposon library in carbapenem-resistant K. pneumoniae, we identified host factors required for phage infection in major Klebsiella phage families. Leveraging the diversity of the PhageBank and experimental evolution strategies, we formulated combinations of phages that minimize the occurrence of phage resistance in vitro. Optimized bacteriophage cocktails selectively suppressed the burden of multi-drug resistant K. pneumoniae in the mouse gut microbiome and drove bacterial populations to lose key virulence factors that act as phage receptors. Further, phage-mediated diversification of bacterial populations in the gut enabled co-evolution of phage variants with higher virulence and a broader host range. Altogether, the Klebsiella PhageBank represents a roadmap for both phage researchers and clinicians to enable phage therapy against a critical multidrug-resistant human pathogen.
2024-10-01 | GSE272297 | GEO
Project description:Genomic epidemiology, virulence and antimicrobial resistance of the multi-host pathogen Streptococcus canis
| PRJEB55124 | ENA