The EMBL-EBI Job Dispatcher sequence analysis tools framework in 2024

Nucleic Acids Research, Год журнала: 2024, Номер 52(W1), С. W521 - W525

Опубликована: Апрель 10, 2024

Abstract The EMBL-EBI Job Dispatcher sequence analysis tools framework (https://www.ebi.ac.uk/jdispatcher) enables the scientific community to perform a diverse range of analyses using popular bioinformatics applications. Free access and required datasets is provided through user-friendly web applications, as well via RESTful SOAP-based APIs. These are integrated into resources such UniProt, InterPro, ENA Ensembl Genomes. This paper overviews recent improvements Dispatcher, including its brand new website documentation, enhanced visualisations, improved job management, rising trend user reliance on service from low- middle-income regions.

Язык: Английский

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Molecular and cellular evolution of the primate dorsolateral prefrontal cortex

Science, Год журнала: 2022, Номер 377(6614)

Опубликована: Авг. 25, 2022

The granular dorsolateral prefrontal cortex (dlPFC) is an evolutionary specialization of primates that centrally involved in cognition. We assessed more than 600,000 single-nucleus transcriptomes from adult human, chimpanzee, macaque, and marmoset dlPFC. Although most cell subtypes defined transcriptomically are conserved, we detected several exist only a subset species as well substantial species-specific molecular differences across homologous neuronal, glial, non-neural subtypes. latter exemplified by human-specific switching between expression the neuropeptide somatostatin tyrosine hydroxylase, rate-limiting enzyme dopamine production certain interneurons. above also illustrated neuropsychiatric risk gene

Язык: Английский

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Database Resources of the National Genomics Data Center, China National Center for Bioinformation in 2024

Nucleic Acids Research, Год журнала: 2023, Номер 52(D1), С. D18 - D32

Опубликована: Ноя. 29, 2023

Abstract The National Genomics Data Center (NGDC), which is a part of the China for Bioinformation (CNCB), provides family database resources to support global academic and industrial communities. With rapid accumulation multi-omics data at an unprecedented pace, CNCB-NGDC continuously expands updates core through big archiving, integrative analysis value-added curation. Importantly, NGDC collaborates closely with major international databases initiatives ensure seamless exchange interoperability. Over past year, significant efforts have been dedicated integrating diverse omics data, synthesizing expanding knowledge, developing new resources, upgrading existing resources. Particularly, several are newly developed biodiversity protists (P10K), bacteria (NTM-DB, MPA) as well plant (PPGR, SoyOmics, PlantPan) disease/trait association (CROST, HervD Atlas, HALL, MACdb, BioKA, RePoS, PGG.SV, NAFLDkb). All services publicly accessible https://ngdc.cncb.ac.cn.

Язык: Английский

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Direct activation of a bacterial innate immune system by a viral capsid protein

Nature, Год журнала: 2022, Номер 612(7938), С. 132 - 140

Опубликована: Ноя. 16, 2022

Abstract Bacteria have evolved diverse immunity mechanisms to protect themselves against the constant onslaught of bacteriophages 1–3 . Similar how eukaryotic innate immune systems sense foreign invaders through pathogen-associated molecular patterns 4 (PAMPs), many bacterial that respond bacteriophage infection require phage-specific triggers be activated. However, identities such and sensing remain largely unknown. Here we identify investigate anti-phage function CapRel SJ46 , a fused toxin–antitoxin system protects Escherichia coli phages. Using genetic, biochemical structural analyses, demonstrate C-terminal domain regulates toxic N-terminal region, serving as both antitoxin phage sensor. Following by certain phages, newly synthesized major capsid protein binds directly relieve autoinhibition, enabling toxin pyrophosphorylate tRNAs, which blocks translation restrict viral infection. Collectively, our results reveal mechanism senses conserved, essential component suggesting PAMP-like model for toxin–antitoxin-mediated in bacteria. We provide evidence CapRels their phage-encoded are engaged ‘Red Queen conflict’ 5 revealing new front intense coevolutionary battle between phages Given proteins some viruses known stimulate signalling mammalian hosts 6–10 deeply conserved facet immunity.

Язык: Английский

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Bacteriophages inhibit and evade cGAS-like immune function in bacteria

Cell, Год журнала: 2023, Номер 186(4), С. 864 - 876.e21

Опубликована: Фев. 1, 2023

A fundamental strategy of eukaryotic antiviral immunity involves the cGAS enzyme, which synthesizes 2′,3′-cGAMP and activates effector STING. Diverse bacteria contain cGAS-like enzymes that produce cyclic oligonucleotides induce anti-phage activity, known as CBASS. However, this activity has only been demonstrated through heterologous expression. Whether harboring CBASS antagonize co-evolve with phages is unknown. Here, we identified an endogenous enzyme in Pseudomonas aeruginosa generates 3′,3′-cGAMP during phage infection, signals to a phospholipase effector, limits replication. In response, express anti-CBASS protein ("Acb2") forms hexamer three molecules reduces activity. Acb2 also binds produced by other bacterial (3',3'-cUU/UA/UG/AA) mammalian (2′,3′-cGAMP), suggesting broad inhibition cGAS-based immunity. Upon deletion, blocks lytic replication lysogenic induction, but rare evade major capsid gene mutations. Altogether, demonstrate function strategies evasion.

Язык: Английский

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Emergent coexistence in multispecies microbial communities

Science, Год журнала: 2023, Номер 381(6655), С. 343 - 348

Опубликована: Июль 20, 2023

Understanding the mechanisms that maintain microbial biodiversity is a critical aspiration in ecology. Past work on coexistence has largely focused species pairs, but it unclear whether pairwise isolation required for multispecies community. To address this question, we conducted hundreds of competition experiments among stably coexisting members 12 different enrichment communities vitro. determine outcomes these experiments, developed an automated image analysis pipeline to quantify abundances. We found competitive exclusion was most common outcome, and strongly hierarchical transitive. Because many coexist within stable community fail co-culture under identical conditions, concluded emergent phenomenon. This highlights importance context understanding origins complex ecosystems.

Язык: Английский

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A genomic catalogue of soil microbiomes boosts mining of biodiversity and genetic resources

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Ноя. 11, 2023

Abstract Soil harbors a vast expanse of unidentified microbes, termed as microbial dark matter, presenting an untapped reservoir biodiversity and genetic resources, but has yet to be fully explored. In this study, we conduct large-scale excavation soil matter by reconstructing 40,039 metagenome-assembled genome bins (the SMAG catalogue) from 3304 metagenomes. We identify 16,530 21,077 species-level (SGBs) unknown SGBs (uSGBs), which expand archaeal bacterial diversity across the tree life. also illustrate pivotal role uSGBs in augmenting microbiome’s functional landscape intra-species diversity, providing large proportions 43,169 biosynthetic gene clusters 8545 CRISPR-Cas genes. Additionally, determine that contributed 84.6% previously unexplored viral-host associations catalogue. The catalogue provides useful genomic resource for further studies investigating resources.

Язык: Английский

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High-throughput functional analysis of autism genes in zebrafish identifies convergence in dopaminergic and neuroimmune pathways

Cell Reports, Год журнала: 2023, Номер 42(3), С. 112243 - 112243

Опубликована: Март 1, 2023

Advancing from gene discovery in autism spectrum disorders (ASDs) to the identification of biologically relevant mechanisms remains a central challenge. Here, we perform parallel vivo functional analysis 10 ASD genes at behavioral, structural, and circuit levels zebrafish mutants, revealing both unique overlapping effects loss function. Whole-brain mapping identifies forebrain cerebellum as most significant contributors brain size differences, while regions involved sensory-motor control, particularly dopaminergic regions, are associated with altered baseline activity. Finally, show global increase microglia resulting function select implicating neuroimmune dysfunction key pathway biology.

Язык: Английский

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Translation of non-canonical open reading frames as a cancer cell survival mechanism in childhood medulloblastoma

Molecular Cell, Год журнала: 2024, Номер 84(2), С. 261 - 276.e18

Опубликована: Янв. 1, 2024

A hallmark of high-risk childhood medulloblastoma is the dysregulation RNA translation. Currently, it unknown whether dysregulates translation putatively oncogenic non-canonical open reading frames (ORFs). To address this question, we performed ribosome profiling 32 tissues and cell lines observed widespread ORF We then developed a stepwise approach using multiple CRISPR-Cas9 screens to elucidate ORFs putative microproteins implicated in survival. determined that lncRNA-ORFs upstream (uORFs) exhibited selective functionality independent main coding sequences. microprotein encoded by one these ORFs, ASNSD1-uORF or ASDURF, was upregulated, associated with MYC-family oncogenes, promoted survival through engagement prefoldin-like chaperone complex. Our findings underscore fundamental importance provide rationale include future studies seeking define new cancer targets.

Язык: Английский

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An engineered enzyme embedded into PLA to make self-biodegradable plastic

Nature, Год журнала: 2024, Номер 631(8022), С. 884 - 890

Опубликована: Июль 17, 2024

Язык: Английский

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