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Article
| Open AccessA conserved Pol II elongator SPT6L mediates Pol V transcription to regulate RNA-directed DNA methylation in Arabidopsis
How to facilitate the transcription of plant-specific RNA Pol V is largely unknown. Liu et al. find that a conserved RNA Pol II elongator, SPT6L, mediates DNA methylation by its association with Pol V and promoting the production of scaffold RNA.
- Yujuan Liu
- , Jie Shu
- & Chen Chen
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Article
| Open AccessSynergizing habits and goals with variational Bayes
Intelligent agents can perform two types of behavior, habitual and goal-directed. The authors propose a deep learning framework using a variational Bayes approach, which computationally explains many aspects of the interaction between the two types of behaviors in sensorimotor tasks.
- Dongqi Han
- , Kenji Doya
- & Jun Tani
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Article
| Open AccessRab30 facilitates lipid homeostasis during fasting
Despite the importance of Rab GTPases in maintaining the integrity of vesicle trafficking, their physiological roles are not well understood. Here, the authors define a role for Rab30 in supporting lipid homeostasis during fasting in the mouse.
- Danielle M. Smith
- , Brian Y. Liu
- & Michael J. Wolfgang
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Article
| Open AccessA variational expectation-maximization framework for balanced multi-scale learning of protein and drug interactions
Multi-scale learning still struggles with imbalanced information and greedy characteristics. Here the authors present MUSE, an Expectation-Maximization-based multi-scale framework, improving predictions across molecular interactions and atomic interfaces.
- Jiahua Rao
- , Jiancong Xie
- & Yuedong Yang
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Article
| Open AccessLipidome atlas of the adult human brain
While our brain is primarily composed of lipids, their functions have largely remained unexplored. Here, authors show that specific lipids can be linked to the structural organization and functional hierarchy of the human and macaque brain.
- Maria Osetrova
- , Anna Tkachev
- & Philipp Khaitovich
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Article
| Open Access9-fold symmetry is not essential for centriole elongation and formation of new centriole-like structures
In this study, the authors show that centriole 9-fold microtubule symmetry is not essential for centriole elongation, correct distribution of the centriole’s components along its length, and in initiating aspects of centriole duplication.
- Pallavi Panda
- , Mark S. Ladinsky
- & David M. Glover
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Article
| Open AccessNeuronal activation sequences in lateral prefrontal cortex encode visuospatial working memory during virtual navigation
The neural codes underlying working memory are not fully understood. Here the authors recorded neurons in the lateral prefrontal cortex of male macaque monkeys, during a working memory task, and identify activation sequences that encode target locations in the task.
- Alexandra Busch
- , Megan Roussy
- & Julio C. Martinez-Trujillo
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Article
| Open AccessLateral parabrachial FoxP2 neurons regulate respiratory responses to hypercapnia
The parabrachial nucleus contains separate populations of neurons that respond to elevated CO2 with EEG arousal and increased breathing. Here we report that the parabrachial respiratory neurons express FoxP2 and are required for respiratory responses to elevated CO2.
- Satvinder Kaur
- , Nicole Lynch
- & Clifford B. Saper
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Article
| Open AccessDuality between predictability and reconstructability in complex systems
Reconstructing the structure of a complex networked system and predicting its time evolution to understand its functions are usually two subjects that are treated separately. The authors propose a theoretical framework based on information theory, that uncovers the relation between reconstructability and predictability in networked systems.
- Charles Murphy
- , Vincent Thibeault
- & Patrick Desrosiers
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Article
| Open AccessContractile injection systems facilitate sporogenic differentiation of Streptomyces davawensis through the action of a phage tapemeasure protein-related effector
Bacteria can use contractile injection systems, similar to viral tail structures, to deliver toxic proteins into other cells. Here, Nagakubo et al. identify a related system that modulates sporulation in multicellular Streptomyces bacteria.
- Toshiki Nagakubo
- , Tatsuya Nishiyama
- & Masanori Toyofuku
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Article
| Open AccessConvergent evolution of fern nectaries facilitated independent recruitment of ant-bodyguards from flowering plants
Some plants use nectar to attract ant bodyguards. Here, the authors use a cross-kingdom phylogenetic approach to find that ferns and angiosperms evolved nectaries in the Cretaceous, coinciding with ant evolution, and that ferns recruited ant-bodyguards from existing ant-angiosperm partnerships.
- Jacob S. Suissa
- , Fay-Wei Li
- & Corrie S. Moreau
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Article
| Open AccessEnvironment modulates protein heterogeneity through transcriptional and translational stop codon readthrough
This study unveils that stop codon readthrough is prevalent in E. coli, particularly under stress conditions. It highlights the influence of stop codon type and genetic context, with both transcriptional and translational origins.
- Maria Luisa Romero Romero
- , Jonas Poehls
- & Agnes Toth-Petroczy
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Article
| Open AccessHDAC activity is dispensable for repression of cell-cycle genes by DREAM and E2F:RB complexes
Here, the authors investigate the interplay among DREAM, RB, SIN3 proteins, and HDACs in the context of cell-cycle gene repression, suggesting that E2F:RB and DREAM complexes can repress cell-cycle genes without relying on HDAC activity.
- Alison K. Barrett
- , Manisha R. Shingare
- & Gerd A. Müller
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Article
| Open AccessDeleting the mitochondrial respiration negative regulator MCJ enhances the efficacy of CD8+ T cell adoptive therapies in pre-clinical studies
Treatment failure following chimaeric antigen receptor (CAR) T cell therapy is common yet incompletely understood. In this study, the authors demonstrate that deletion of the mitochondrial negative regulator, MCJ, in CAR T cells promotes target cell killing ex vivo and augments their efficacy in an in vivo B cell leukaemia model.
- Meng-Han Wu
- , Felipe Valenca-Pereira
- & Mercedes Rincon
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Article
| Open AccessValidation of human telomere length multi-ancestry meta-analysis association signals identifies POP5 and KBTBD6 as human telomere length regulation genes
Here the authors conduct a multi-ancestry meta-analysis of telomere length, used diverse approaches to identify genes underlying association signals, and experimentally validated POP5 and KBTBD6 as regulators of telomere length in human cells.
- Rebecca Keener
- , Surya B. Chhetri
- & Alexis Battle
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Article
| Open AccessBiochemical-free enrichment or depletion of RNA classes in real-time during direct RNA sequencing with RISER
It is difficult to detect low abundance RNAs in sequencing experiments, and biochemical methods to enrich or deplete specific RNAs are time-consuming, costly and can damage RNA. Here, authors develop a biochemical-free technology to enrich or deplete RNA classes in real-time during direct RNA sequencing.
- Alexandra Sneddon
- , Agin Ravindran
- & Eduardo Eyras
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Article
| Open AccessPhylogenomics reveals the evolutionary origins of lichenization in chlorophyte algae
Lichen symbiosis between chlorophyte algae and fungi is a key player in ecosystems but our understanding of its evolution and genetic regulation in algae remains limited. This study finds that lichen symbiosis evolved at least three times in algae through gene family expansion and horizontal gene transfers
- Camille Puginier
- , Cyril Libourel
- & Jean Keller
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Article
| Open AccessMultispecies deep learning using citizen science data produces more informative plant community models
By modelling the distribution of the entire Swiss flora using deep learning and citizen science data, this study demonstrates a method that predicts flowering phenology and potentially dominant tree species more accurately than commonly used approaches. This approach could enable investigation of understudied aspects of ecology and refine our understanding of plant distributions.
- Philipp Brun
- , Dirk N. Karger
- & Niklaus E. Zimmermann
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Article
| Open AccessRelative dispersion ratios following fecal microbiota transplant elucidate principles governing microbial migration dynamics
Microbial migration profoundly impacts ecosystems. Here, the authors introduce a statistical approach to explore microbial dispersion following fecal microbiota transplant, uncovering dependencies between colonizing taxa, with insights into community dynamics.
- Yadid M. Algavi
- & Elhanan Borenstein
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Article
| Open AccessHeterogeneity in strategy use during arbitration between experiential and observational learning
People learn by observing others and from personal experience, but which strategy they favor varies. Here, the authors show that while some people dynamically arbitrate and switch to the strategy that is most reliable, others preferentially use one or a fixed mixture of strategies.
- Caroline J. Charpentier
- , Qianying Wu
- & John P. O’Doherty
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Article
| Open AccessUltrafast energy quenching mechanism of LHCSR3-dependent photoprotection in Chlamydomonas
The Light Harvesting Complex Stress-Related Protein (LHCSR) can protect algae from severe photodamage via energy-dependent quenching (qE). Here, the authors find that a photoproduct of carotenoid S1 state is populated in qE and depopulated in 7.5 ps.
- Mengyuan Zheng
- , Xiaojie Pang
- & Lijin Tian
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Article
| Open AccessImmune features are associated with response to neoadjuvant chemo-immunotherapy for muscle-invasive bladder cancer
In the phase 2 study LCCC1520 (NCT02690558), clinical activity of pembrolizumab in combination with gemcitabine and cisplatin as neoadjuvant therapy in patients with muscle-invasive bladder cancer has been reported. Here the authors present molecular and immune cellular features associated with response to neoadjuvant chemo-immunotherapy.
- Wolfgang Beckabir
- , Mi Zhou
- & Benjamin G. Vincent
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Article
| Open AccessH2AX promotes replication fork degradation and chemosensitivity in BRCA-deficient tumours
Histone H2AX has a known role in DNA damage repair but interestingly, its loss is associated with resistance to poly(ADP-ribose) polymerase (PARP) inhibition in BRCA-deficient tumours. Here, the authors identify a role of γH2AX in the degradation of replication forks and demonstrate that H2AX loss drives PARP inhibitor resistance via increased stressed fork stability in BRCA-deficient tumours.
- Diego Dibitetto
- , Martin Liptay
- & Sven Rottenberg
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Article
| Open AccessPhosphorus deficiency alleviates iron limitation in Synechocystis cyanobacteria through direct PhoB-mediated gene regulation
Iron and phosphorus exist at low concentrations in surface waters and may be co-limiting resources for phytoplankton growth. Here, the authors show that phosphorus deficiency increases the growth of iron-limited cyanobacteria through a PhoB-mediated regulatory network.
- Guo-Wei Qiu
- , Wen-Can Zheng
- & Bao-Sheng Qiu
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Article
| Open AccessHyperactivity of indirect pathway-projecting spiny projection neurons promotes compulsive behavior
Striatal hyperactivity has been linked to compulsive behavior, but cell-type and pathway specific mechanisms are unclear. Here, the authors show excessive grooming in Sapap3-KO mice is associated with indirect pathway hyperactivity and suppression of hyperactivity normalizes grooming.
- Sean C. Piantadosi
- , Elizabeth E. Manning
- & Susanne E. Ahmari
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Article
| Open AccessThe adaptive value of density-dependent habitat specialization and social network centrality
Social behavior and habitat specialization are often linked through density-dependence and their effects on fitness. Here, the authors show that in caribou, these traits are density-dependent, but only habitat specialization has an effect on fitness.
- Quinn M. R. Webber
- , Michel P. Laforge
- & Eric Vander Wal
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Article
| Open AccessStructure and inhibition of the human lysosomal transporter Sialin
Sialin transports multiple substrates including sialic acid out of lysosomes, and neurotransmitters into synaptic vesicles. This study reports the cryo-EM structures of Sialin in multiple states revealing its transport and pH-sensing mechanisms.
- Philip Schmiege
- , Linda Donnelly
- & Xiaochun Li
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Article
| Open AccessImpact of secretin receptor homo-dimerization on natural ligand binding
GPCRs can form functionally important dimers. Here, authors study impact of dimerization of the secretin receptor on peptide ligand binding and show high receptor conformational dynamics that facilitate G protein recruitment and activation.
- Kaleeckal G. Harikumar
- , Sarah J. Piper
- & Laurence J. Miller
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Article
| Open AccessAutophagy-deficient macrophages exacerbate cisplatin-induced mitochondrial dysfunction and kidney injury via miR-195a-5p-SIRT3 axis
Tubulointerstitial inflammation occurs frequently in acute kidney injury (AKI), and Mφ autophagy is a known contributor to inflammation-related diseases. Here, Yuan et al. show that Mφ autophagy deficiency induces systemic inflammation, impairs mitochondria, and worsens kidney injury in AKI mice.
- Yujia Yuan
- , Longhui Yuan
- & Yanrong Lu
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Article
| Open AccessAngle between DNA linker and nucleosome core particle regulates array compaction revealed by individual-particle cryo-electron tomography
Here, using cryo-ET, the 3D structures of individual nucleosome particles were characterized to observe changes under varying ionic strengths and in the presence of protein H1, revealing key regulatory roles in chromatin organization dynamics.
- Meng Zhang
- , César Díaz-Celis
- & Gang Ren
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Article
| Open AccessZO-1 interacts with YB-1 in endothelial cells to regulate stress granule formation during angiogenesis
ZO-1, a cell junction protein, is essential for angiogenesis. Here the authors identify in endothelial cells unexpected associations of ZO-1 with stress granule proteins, such as YB-1, that are crucial for cytoprotection, implicating the ZO-1-YB-1 interaction in angiogenesis.
- Yassine El Bakkouri
- , Rony Chidiac
- & Jean-Philippe Gratton
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Article
| Open AccessA comprehensive benchmarking with interpretation and operational guidance for the hierarchy of topologically associating domains
TAD hierarchy demonstrates cell-to-cell variability, leading to the development of numerous callers. Here, authors present a comprehensive benchmark of TAD hierarchy callers and introduce the ‘air conditioner’ model to illustrate TAD hierarchy’s role in transcription.
- Jingxuan Xu
- , Xiang Xu
- & Hebing Chen
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Article
| Open AccessIlluminating the function of the orphan transporter, SLC22A10, in humans and other primates
Orphan transporters can be found in over 20 families in the SLC superfamily. Here, the authors show that human SLC22A10 is a unitary pseudogene due to a fixed missense mutation, P220; while in great apes, its orthologs transport sex steroid conjugates.
- Sook Wah Yee
- , Luis Ferrández-Peral
- & Kathleen M. Giacomini
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Article
| Open AccessDevelopment of a nucleoside-modified mRNA vaccine against clade 2.3.4.4b H5 highly pathogenic avian influenza virus
Highly pathogenic avian influenza viruses from H5 clade 2.3.4.4b are circulating widely in birds and have recently caused large outbreaks in mammals. Here, Furey et al. develop a clade 2.3.4.4b HA-expressing mRNA-LNP vaccine and show that it elicits strong protective immune responses in mice and ferrets.
- Colleen Furey
- , Gabrielle Scher
- & Scott E. Hensley
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Article
| Open AccessEnteric nervous system regeneration and functional cure of experimental digestive Chagas disease with trypanocidal chemotherapy
The digestive form of Chagas disease (American trypanosomiasis) involves damage to the nervous system of the gastrointestinal tract and problems with peristalsis. Here, Khan et al show that infection causes damage to the colon that can be reversed if it is successfully treated early in the process.
- Archie A. Khan
- , Harry C. Langston
- & Michael D. Lewis
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Article
| Open AccessThe patatin-like protein PlpD forms structurally dynamic homodimers in the Pseudomonas aeruginosa outer membrane
The Omp85 superfamily is a widely distributed class of outer membrane proteins found in Gram-negative bacteria, mitochondria and chloroplasts. Here the authors show that PlpD has a different structure and topology than other Omp85 proteins that have been studied.
- Sarah E. Hanson
- , Tyrone Dowdy
- & Harris D. Bernstein
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Article
| Open AccessA rationally designed miniature of soluble methane monooxygenase enables rapid and high-yield methanol production in Escherichia coli
Soluble methane monooxygenase (sMMO) is a potentially value biocatalyst, but production of active recombinant sMMO is very challenging. Here the authors report the rational design and construction of a catalytically active miniature sMMO which enables high-yield production of methanol in E. coli.
- Yeonhwa Yu
- , Yongfan Shi
- & Jeewon Lee
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Article
| Open AccessSolutes unmask differences in clustering versus phase separation of FET proteins
Biomolecular condensates form via phase separation of multivalent macromolecules. Phase separation is governed by solubility whereas multivalence drives percolation, also known as gelation. The authors in this work identify the distinct energy and length scales that influence phase separation versus percolation.
- Mrityunjoy Kar
- , Laura T. Vogel
- & Rohit V. Pappu
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Article
| Open AccessSingle molecule delivery into living cells
Controlled manipulation of cultured cells by delivery of exogenous macromolecules is a cornerstone of experimental biology. Here, the authors describe a platform to deliver defined numbers of macromolecules into cultured cell lines at single molecule resolution.
- Chalmers C. Chau
- , Christopher M. Maffeo
- & Paolo Actis
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Article
| Open AccessThe brain structure, inflammatory, and genetic mechanisms mediate the association between physical frailty and depression
Identifying modifiable risk factors that could prevent depression is important. Here, the authors show increased risks of incident depression in pre-frail and frail individuals and highlight the mediating role of brain structure and inflammation.
- Rongtao Jiang
- , Stephanie Noble
- & Dustin Scheinost
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Article
| Open AccessIn-depth organic mass cytometry reveals differential contents of 3-hydroxybutanoic acid at the single-cell level
Comprehensive single-cell metabolic profiling is critical for revealing phenotypic heterogeneity and elucidating the molecular mechanisms underlying biological processes. Here, the authors establish a novel single-cell metabolomics platform for in-depth organic mass cytometry.
- Shaojie Qin
- , Yi Zhang
- & Yu Bai
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Article
| Open AccessReduction of specific enterocytes from loss of intestinal LGR4 improves lipid metabolism in mice
How LGR4 impacts nutrition absorption and energy homeostasis is unknown. Here, the authors show that LGR4 loss in the intestinal epithelium decreases the proportion of enterocytes selective for long-chain fatty acid absorption, reducing lipid absorption and improving lipid and glucose metabolism.
- Yuan Liang
- , Chao Luo
- & Yue Yin
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Article
| Open AccessSingle-cell and spatial transcriptomics analysis of non-small cell lung cancer
Myeloid cell populations play a critical role in lung cancer progression. Here, the authors use scRNA-seq and spatial transcriptomics to identify changes in the phenotype of macrophages within the tumour microenvironment.
- Marco De Zuani
- , Haoliang Xue
- & Ana Cvejic
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Article
| Open AccessTranslation initiation factor eIF1.2 promotes Toxoplasma stage conversion by regulating levels of key differentiation factors
Wang et al. show that Toxoplasma gondii translation initiation factor eIF1.2 is critical for acute to chronic stage transition during infection, underscoring the importance of protein translation in controlling stage differentiation.
- Fengrong Wang
- , Michael J. Holmes
- & Vern B. Carruthers
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Article
| Open AccessAn integrated spatio-temporal view of riverine biodiversity using environmental DNA metabarcoding
Using intensive eDNA sampling in space and time across five rivers in Europe and North America, this study shows that eDNA gives relevant information on freshwater diversity and ecology across broad taxonomic groups, and with limited downstream transport. The findings demonstrate that eDNA is vital for freshwater biodiversity monitoring in a time of anthropogenic change.
- William Bernard Perry
- , Mathew Seymour
- & Simon Creer
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Article
| Open AccessA nutrient responsive lipase mediates gut-brain communication to regulate insulin secretion in Drosophila
Amplification of glucose stimulated insulin secretion by lipids is not fully understood due to complex inter organ communication in glycemic regulation. Here the authors show Vaha, a Drosophila lipase synthesized in the gut, concentrates in insulin producing cells in the brain to regulate insulin like peptide release.
- Alka Singh
- , Kandahalli Venkataranganayaka Abhilasha
- & Usha R. Acharya
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Article
| Open AccessCompound mortality impacts from extreme temperatures and the COVID-19 pandemic
Extreme weather and pandemics are classified as two of the most serious risks facing the UK in its National Risk Register. Here, the authors investigate the compound mortality impacts of extreme high and low temperatures and COVID-19 in England and Wales.
- Y. T. Eunice Lo
- , Dann M. Mitchell
- & Antonio Gasparrini
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Article
| Open AccessFar-East Asian Toxoplasma isolates share ancestry with North and South/Central American recombinant lineages
The population genome structure of Asian Toxoplasma remains incompletely understood. This study analyzes intercontinental genomic admixture in 17 isolates from Japan and China, providing insights into the evolution of parasites and their impact on public health.
- Fumiaki Ihara
- , Hisako Kyan
- & Masahiro Yamamoto
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Article
| Open AccessPrediction of Klebsiella phage-host specificity at the strain level
Bacterial viruses (phages) are promising alternatives to treat antibiotic-resistant bacterial infections, but finding matching phages against bacteria of interest is challenging. Here, Boeckaerts et al. present a machine learning approach that predicts phage-bacteria pairs at the strain level for Klebsiella pathogens.
- Dimitri Boeckaerts
- , Michiel Stock
- & Yves Briers
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