Mutant IDH1 inhibition induces dsDNA sensing to activate tumor immunity

Science, Год журнала: 2024, Номер 385(6705)

Опубликована: Июль 11, 2024

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Язык: Английский

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zol and fai: large-scale targeted detection and evolutionary investigation of gene clusters

Nucleic Acids Research, Год журнала: 2025, Номер 53(3)

Опубликована: Янв. 24, 2025

Abstract Many universally and conditionally important genes are genomically aggregated within clusters. Here, we introduce fai zol, which together enable large-scale comparative analysis of different types gene clusters mobile-genetic elements, such as biosynthetic (BGCs) or viruses. Fundamentally, they overcome a current bottleneck to reliably perform comprehensive orthology inference at large scale across broad taxonomic contexts thousands genomes. First, allows the identification orthologous instances query cluster interest amongst database target Subsequently, zol enables reliable, context-specific ortholog groups for individual protein-encoding instances. In addition, performs functional annotation computes variety evolutionary statistics each inferred group. Importantly, in comparison tools visual exploration homologous relationships between clusters, can handle produce detailed reports that easy digest. To showcase apply them for: (i) longitudinal tracking virus metagenomes, (ii) performing population genetic investigations BGCs fungal species, (iii) uncovering trends virulence-associated genomes from diverse bacterial genus.

Язык: Английский

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Large-scale computational analyses of gut microbial CAZyme repertoires enabled by Cayman

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Янв. 8, 2024

Abstract Carbohydrate-active enzymes (CAZymes) are crucial for digesting glycans, but bioinformatics tools CAZyme profiling and interpretation of substrate preferences in microbial community data lacking. To address this, we developed a profiler (Cayman) hierarchical annotation scheme. Leveraging these, genomically survey CAZymes human gut microbes (n=107,683 genomes), which suggests novel mucin-foraging species. In subsequent meta-analysis repertoires Western versus non-Western metagenomes (n=4,281) find that richer fibre-degrading despite lower overall richness. We additionally pinpoint the taxonomic drivers underlying these shifts. A second comparing colorectal cancer patients (CRC) to controls (n=1,998) shows CRC deprived dietary fibre-targeting, enriched glycosaminoglycan-targeting CAZymes. genomic analysis co-localizing domains predicts substrates CRC-enriched Cayman is broadly applicable across communities freely available from https://github.com/zellerlab/cayman .

Язык: Английский

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Seed coating with phages for sustainable plant biocontrol of plant pathogens and influence of the seed coat mucilage

Microbial Biotechnology, Год журнала: 2024, Номер 17(6)

Опубликована: Июнь 1, 2024

Pathogens resistant to classical control strategies pose a significant threat crop yield, with seeds being major transmission route. Bacteriophages, viruses targeting bacteria, offer an environmentally sustainable biocontrol solution. In this study, we isolated and characterized two novel phages, Athelas Alfirin, which infect Pseudomonas syringae Agrobacterium fabrum, respectively, included the recently published Pfeifenkraut phage infecting Xanthomonas translucens. Using simple immersion method, phages coated onto successfully lysed bacteria post air-drying. The seed coat mucilage (SCM), polysaccharide-polymer matrix exuded by seeds, plays critical role in binding. Seeds removed formed five 10 times less lysis zones compared those mucilage. podovirus showed highest dependency. Phages from Autographiviridae family also depended on for adhesion. Comparative analysis of Arabidopsis SCM mutants suggested diffusible cellulose as key component Long-term activity tests demonstrated high stability surfaces significantly increasing seedling survival rates presence pathogens. non-virulent host strains enhanced but has potential limitations. These findings highlight phage-based interventions promising, combating pathogen resistance improving yield.

Язык: Английский

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Magnetotactic bacteria from diverse Pseudomonadota families biomineralize intracellular Ca-carbonate

The ISME Journal, Год журнала: 2025, Номер unknown

Опубликована: Янв. 7, 2025

Язык: Английский

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Combined transcriptomic and metabolomic analyses reveal the pharmacognostic mechanism of the metabolism of flavonoids in different parts of Polygonum capitatum

The Plant Genome, Год журнала: 2025, Номер 18(1)

Опубликована: Янв. 14, 2025

Abstract The plant Polygonum capitatum ( P. ) contains a variety of flavonoids that are distributed differently among different parts. Nevertheless, differentially expressed genes (DEGs) associated with this heterogeneous distribution have not been identified. In study, combined transcriptomic and metabonomic analysis, we identified significant DEGs related to variations in flavonoid composition parts . Subsequently, nontargeted metabolomic analyses revealed phenolic acids were significantly enriched the phenylpropanoid biosynthesis, shikimic acid biosynthesis pathways. expression levels encoding enzymes, including shikimate O ‐hydroxycinnamoyltransferase (HCT), chalcone synthase (CHS), 3′,5′‐hydroxylase (CYP75A), flavones 3‐hydroxylase (F3H), flavonol (FLS), leucoanthocyanidin reductase (LAR), trans‐cinnamate 4‐monooxygenase (CYP73A), kinase (SK), found be lowest leaves via quantitative PCR. Interestingly, these involved quality markers such as gallic acid, quercetin, quercitrin Finally, targeted results reconfirmed contents highest This research provides theoretical basis for further understanding differential regulatory mechanism metabolism , providing novel insights into pharmacognostic

Язык: Английский

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Predicting coarse-grained representations of biogeochemical cycles from metabarcoding data

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Abstract Motivation Taxonomic analysis of environmental microbial communities is now routinely performed thanks to advances in DNA sequencing. Determining the role these global biogeochemical cycles requires identification their metabolic functions, such as hydrogen oxidation, sulfur reduction, and carbon fixation. These functions can be directly inferred from metagenomics data, but many applications metabarcoding still method choice. The reconstruction data integration into coarse-grained representations geobiochemical remains a difficult bioinformatics problem today. Results We developed pipeline, called Tabigecy, which exploits taxonomic affiliations predict constituting cycles. In first step, Tabigecy uses tool EsMeCaTa consensus proteomes input affiliations. To optimise this process, we generated precomputed database containing information about 2,404 taxa UniProt. are searched using bigecyhmm, newly Python package relying on Hidden Markov Models identify key enzymes involved function then projected representation applied two salt cavern datasets validated its predictions with activity hydrochemistry measurements samples. results highlight utility approach investigate impact processes.

Язык: Английский

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sORFdb – a database for sORFs, small proteins, and small protein families in bacteria

BMC Genomics, Год журнала: 2025, Номер 26(1)

Опубликована: Фев. 5, 2025

Abstract Small proteins with fewer than 100, particularly 50, amino acids are still largely unexplored. Nonetheless, they represent an essential part of bacteria’s often neglected genetic repertoire. In recent years, the development ribosome profiling protocols has led to detection increasing number previously unknown small proteins. Despite this, overlooked in many cases by automated genome annotation pipelines, and often, no functional descriptions can be assigned due a lack known homologs. To understand overcome these limitations, current abundance existing databases was evaluated, new dedicated database for their potential functions, called ’sORFdb’, created. this end, were extracted from annotated bacterial genomes GenBank database. Subsequently, quality-filtered, compared, complemented Swiss-Prot, UniProt, SmProt ensure reliable identification characterization Families similar created using bidirectional best BLAST hits followed Markov clustering. Analysis public revealed that is limited historical technical constraints. Additionally, missing despite presence As expected, taxonomic bias evident over-represented clinically relevant bacteria. This comprehensive accessible via feature-rich website providing specialized search features sORFs high quality. protein families Hidden Models information on distribution other physicochemical properties available. conclusion, novel sORFdb specialized, taxonomy-independent improves findability classification sORFs, proteins, functions bacteria, thereby supporting future consistent annotation. All data freely https://sorfdb.computational.bio .

Язык: Английский

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Six Novel Pseudomonas aeruginosa Phages: Genomic Insights and Therapeutic Potential

PHAGE, Год журнала: 2025, Номер unknown

Опубликована: Фев. 21, 2025

Introduction: Pseudomonas aeruginosa is an opportunistic pathogen that causes health care-associated infections. The rise of antibiotic-resistant bacterial strains necessitates alternative treatment strategies, with bacteriophage therapy being a promising approach.

Язык: Английский

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An algorithm for annotation and classification of T. cruzi MASP sequences: towards a better understanding of the parasite genetic variability

BMC Genomics, Год журнала: 2025, Номер 26(1)

Опубликована: Фев. 24, 2025

Trypanosoma cruzi, the protozoan causing Chagas disease, is responsible for a neglected tropical disease affecting millions in Latin America. Its genome contains rapidly evolving multigene families, such as mucins (TcMUC), trans-sialidases (TS), and mucin-associated surface proteins (MASP), which are essential parasite transmission mechanisms. However, methodological challenges assembly annotation have limited characterization of these gene particularly MASPs. We developed bioinformatic pipeline automatic identification, characterization, MASPs directly from T. cruzi assemblies. This algorithm, based on manually curated MASP database HMM-based identification diagnostic motifs, enables robust classification molecules into canonical MASPs, MASP-related (mostly pseudogenes), chimeric sequences combining TcMUC/TS genes. Validation against rigorously annotated dataset demonstrated high accuracy, allowed us to reclassify misanotated and, more crucially, accurately identify previously unrecognized chimeras. algorithm was then used explore repertoire genomes 13 strains different evolutionary lineages, revealing patterns diversity. For instance, TcI TcII exhibited higher ratios MASP/MASP-related greater abundance chimeras, suggesting that their under strong selective pressures towards maintaining broader panel full-length genes at expense pseudogenes. On contrary, structural features sequences, MASP-chimeras were largely conserved across genomes. novel automates key protein family unique improving enabling comparative analyses. It provides an tool exploring dynamics families could be extended other families.

Язык: Английский

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