ColabFold: making protein folding accessible to all

Nature Methods, Год журнала: 2022, Номер 19(6), С. 679 - 682

Опубликована: Май 30, 2022

Abstract ColabFold offers accelerated prediction of protein structures and complexes by combining the fast homology search MMseqs2 with AlphaFold2 or RoseTTAFold. ColabFold’s 40−60-fold faster optimized model utilization enables close to 1,000 per day on a server one graphics processing unit. Coupled Google Colaboratory, becomes free accessible platform for folding. is open-source software available at https://github.com/sokrypton/ColabFold its novel environmental databases are https://colabfold.mmseqs.com .

Язык: Английский

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ColabFold - Making protein folding accessible to all

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2021, Номер unknown

Опубликована: Авг. 15, 2021

ColabFold offers accelerated protein structure and complex predictions by combining the fast homology search of MMseqs2 with AlphaFold2 or RoseTTAFold. ColabFold’s 40 - 60× faster optimized model use allows predicting close to a thousand structures per day on server one GPU. Coupled Google Colaboratory, becomes free accessible platform for folding. is open-source software available at github.com/sokrypton/ColabFold . Its novel environmental databases are colabfold.mmseqs.com Contact [email protected] , [email protected] [email protected]

Язык: Английский

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Phage therapy: From biological mechanisms to future directions

Cell, Год журнала: 2023, Номер 186(1), С. 17 - 31

Опубликована: Янв. 1, 2023

Increasing antimicrobial resistance rates have revitalized bacteriophage (phage) research, the natural predators of bacteria discovered over 100 years ago. In order to use phages therapeutically, they should (1) preferably be lytic, (2) kill bacterial host efficiently, and (3) fully characterized exclude side effects. Developing therapeutic takes a coordinated effort multiple stakeholders. Herein, we review state art in phage therapy, covering biological mechanisms, clinical applications, remaining challenges, future directions involving naturally occurring genetically modified or synthetic phages.

Язык: Английский

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IMG/VR v4: an expanded database of uncultivated virus genomes within a framework of extensive functional, taxonomic, and ecological metadata

Nucleic Acids Research, Год журнала: 2022, Номер 51(D1), С. D733 - D743

Опубликована: Ноя. 18, 2022

Viruses are widely recognized as critical members of all microbiomes. Metagenomics enables large-scale exploration the global virosphere, progressively revealing extensive genomic diversity viruses on Earth and highlighting myriad ways by which impact biological processes. IMG/VR provides access to largest collection viral sequences obtained from (meta)genomes, along with functional annotation rich metadata. A web interface users efficiently browse search based genome features and/or sequence similarity. Here, we present fourth version IMG/VR, composed >15 million virus genomes fragments, a ≈6-fold increase in size compared previous version. These clustered into 8.7 operational taxonomic units, including 231 408 at least one high-quality representative. Viral now systematically identified genomes, metagenomes, metatranscriptomes using new detection approach (geNomad), IMG standard complemented quality estimation CheckV, classification reflecting latest standards, microbial host taxonomy prediction. v4 is available https://img.jgi.doe.gov/vr, underlying data download https://genome.jgi.doe.gov/portal/IMG_VR.

Язык: Английский

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Gut Microbiota Interact With the Brain Through Systemic Chronic Inflammation: Implications on Neuroinflammation, Neurodegeneration, and Aging

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Апрель 7, 2022

It has been noticed in recent years that the unfavorable effects of gut microbiota could exhaust host vigor and life, yet knowledge theory are just beginning to be established. Increasing documentation suggests microbiota–gut–brain axis not only impacts brain cognition psychiatric symptoms but also precipitates neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s (PD), multiple sclerosis (MS). How blood–brain barrier (BBB), a machinery protecting central nervous system (CNS) from systemic circulation, allows risky factors derived translocated into seems paradoxical. For unique anatomical, histological, immunological properties underpinning its permeable dynamics, BBB regarded biomarker associated with neural pathogenesis. The permeability mice rats caused by GM dysbiosis raises question how metabolites change causes pathophysiology neuroinflammation neurodegeneration (NF&ND) aging, pivotal multidisciplinary field tightly immune chronic inflammation. If all, microbiota-induced inflammation (GM-SCI) mainly refers excessive mucosal immunity dysregulation, which is often influenced dietary components age, produced at interface intestinal (IB) or exacerbated after IB disruption, initiates various common diseases along dispersal routes, eventually impairs integrity cause NF&ND aging. To illustrate roles affected inflammatory “leaky” resulting their metabolites, we reviewed selected publications, including role barrier, influences on permeability, NF&ND, add depth bridging inflammation, plausible mechanism indispensable for corruption was highlighted; namely, maintenance cues cytokines, may help understand play major

Язык: Английский

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iPHoP: An integrated machine learning framework to maximize host prediction for metagenome-derived viruses of archaea and bacteria

PLoS Biology, Год журнала: 2023, Номер 21(4), С. e3002083 - e3002083

Опубликована: Апрель 21, 2023

The extraordinary diversity of viruses infecting bacteria and archaea is now primarily studied through metagenomics. While metagenomes enable high-throughput exploration the viral sequence space, metagenome-derived sequences lack key information compared to isolated viruses, in particular host association. Different computational approaches are available predict host(s) uncultivated based on their genome sequences, but thus far individual limited either precision or recall, i.e., for a number they yield erroneous predictions no prediction at all. Here, we describe iPHoP, two-step framework that integrates multiple methods reliably taxonomy genus rank broad range archaea, while retaining low false discovery rate. Based large dataset virus genomes from IMG/VR database, illustrate how iPHoP can provide extensive guide further characterization viruses.

Язык: Английский

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The gut virome: A new microbiome component in health and disease

EBioMedicine, Год журнала: 2022, Номер 81, С. 104113 - 104113

Опубликована: Июнь 23, 2022

The human gastrointestinal tract harbours an abundance of viruses, collectively known as the gut virome. virome is highly heterogeneous across populations and linked to geography, ethnicity, diet, lifestyle, urbanisation. currently function varies greatly populations, much remains unknown. We review current literature on virome, intricate trans-kingdom interplay among bacteria, mammalian host underlying health diseases. summarise evidence use diagnostic markers a therapeutic target. shed light novel avenues microbiome-inspired diagnosis therapies. also pre-clinical clinical studies virome-rectification-based therapies, including faecal microbiota transplantation, refined phage therapy. Our suggests that future research effort should focus unravelling mechanisms exerted by viruses/phages in pathophysiology, developing phage-prompted precision

Язык: Английский

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Ultra-deep sequencing of Hadza hunter-gatherers recovers vanishing gut microbes

Cell, Год журнала: 2023, Номер 186(14), С. 3111 - 3124.e13

Опубликована: Июнь 21, 2023

The gut microbiome modulates immune and metabolic health. Human data are biased toward industrialized populations, limiting our understanding of non-industrialized microbiomes. Here, we performed ultra-deep metagenomic sequencing on 351 fecal samples from the Hadza hunter-gatherers Tanzania comparative populations in Nepal California. We recovered 91,662 genomes bacteria, archaea, bacteriophages, eukaryotes, 44% which absent existing unified datasets. identified 124 gut-resident species vanishing highlighted distinct aspects related to situ replication rates, signatures selection, strain sharing. Industrialized microbes were found be enriched genes associated with oxidative stress, possibly a result adaptation inflammatory processes. This unparalleled view provides valuable resource, expands capable colonizing human gut, clarifies extensive perturbation induced by lifestyle.

Язык: Английский

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Microbiome-based interventions to modulate gut ecology and the immune system

Mucosal Immunology, Год журнала: 2022, Номер 15(6), С. 1095 - 1113

Опубликована: Сен. 30, 2022

The gut microbiome lies at the intersection between environment and host, with ability to modify host responses disease-relevant exposures stimuli. This is evident in how enteric microbes interact immune system, e.g., supporting maturation early life, affecting drug efficacy via modulation of responses, or influencing development cell populations their mediators. Many factors modulate ecosystem dynamics during daily life we are just beginning realise therapeutic prophylactic potential microbiome-based interventions. These approaches vary application, goal, mechanisms action. Some entire community, such as nutritional faecal microbiota transplantation, while others, phage therapy, probiotics, prebiotics, target specific taxa strains. In this review, assessed experimental evidence for interventions, a particular focus on clinical relevance, ecological effects, system.

Язык: Английский

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The Mechanism of Bacterial Resistance and Potential Bacteriostatic Strategies

Antibiotics, Год журнала: 2022, Номер 11(9), С. 1215 - 1215

Опубликована: Сен. 8, 2022

Bacterial drug resistance is rapidly developing as one of the greatest threats to human health. Bacteria will adopt corresponding strategies crack inhibitory effect antibiotics according antibacterial mechanism antibiotics, involving mutation target, secreting hydrolase, and discharging out cells through an efflux pump, etc. In recent years, bacteria are found constantly evolve new mechanisms including target protective protein, changes in cell morphology, so on, endowing them with multiple defense systems against leading emergence multi-drug resistant (MDR) unavailability drugs clinics. Correspondingly, researchers attempt uncover mystery bacterial develop more convenient effective strategies. Although traditional still play a significant role treatment diseases caused by sensitive pathogenic bacteria, they gradually lose efficacy MDR bacteria. Therefore, highly compounds, such phage therapy CRISPER-Cas precision therapy, gaining increasing amount attention, considered be treatments moist potential regard future. this review, nine identified summarized, which enhance retention rate under action promote distribution drug-resistant (DRB) population. Afterwards, three kinds methods introduced, compounds exhibit broad application prospects different mechanisms, has been successfully applied infectious super technology can edit genes at gene level, high accuracy flexibility. These provide options for clinical treatment, greatly alleviate current crisis.

Язык: Английский

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