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Oba, K.

Publications and source records attributed to Oba, K..

4 recordsLinked to original sources

Delphy: scalable, near-real-time Bayesian phylogenetics for outbreaks

Pathogen genomic analysis is central to tracking, understanding, and containing outbreaks, but complexity and high costs of state-of-the-art (SOTA) phylogenetic tools limit global access and impact. We introduce Delphy, an exact reformulation of Bayesian phylogenetics designed to transform its speed, scalability and accessibility while retaining SOTA accuracy. Delphys central data structure, an Explicit Mutation Annotated Tree, exploits the high sequence similarity in large-scale epidemic datasets for efficient tree exploration and convergence. By reproducing key analyses from recent major epidemics (Ebola, Zika, SARS-CoV-2, mpox, and H5N1), we demonstrate SOTA accuracy with up to 1,000x speedups. Assessing Delphys scalability, we show that a simulated dataset of 100,000 sequences can be analyzed in under a day-the largest such computation to date. We distribute Delphy as a client-side web application, enabling users worldwide to turn raw data into interactive results within minutes, without the data ever leaving the users machine. Delphy automatically identifies key viral lineages and mutations, as well as their emergence and prevalence through time, all with quantified uncertainties derived from a solid theoretical foundation. Delphy shows the power of Bayesian phylogenetics as a fast, accessible frontline tool for tackling future outbreaks.

genomics↗

Meta-omic insights into active bacteria mediating N2O mitigation and dissimilatory nitrate reduction to ammonium in an ammonia recovery bioreactor

Shifting from ammonia removal to recovery is the current strategy in wastewater treatment management. We recently developed a microaerophilic activated sludge (MAS) system for retaining ammonia while removing organic carbon with minimal N2O emissions. A comprehensive understanding of nitrogen metabolisms in the MAS system is essential to optimize system performance. Here, we employed metagenomics and metatranscriptomics analyses to characterize the microbial community structure and activity during the transition from a microaerophilic to an aerobic condition. A hybrid approach of high-quality Illumina short reads and Nanopore long reads recovered medium-to high-quality 98 non-redundant metagenome-assembled genomes (MAGs) from the MAS communities. The suppressed bacterial ammonia monooxygenase (amoA) expression was upregulated after shifting from a microaerophilic to an aerobic condition. The 73 MAGs (>74% of the total) from 11 bacterial phyla harbored genes encoding proteins involved in nitrate respiration; 39 MAGs ([~]53%) carried N2O reductase (nosZ) genes with the predominance of clade II nosZ (31 MAGs), and 24 MAGs ([~]33%) possessed nitrite reductase (ammonia forming) genes (nrfA). Clade II nosZ and nrfA genes exhibited the highest and second-highest expressions among nitrogen metabolism genes, indicating robust N2O consumption and ammonification. Non-denitrifying clade II nosZ bacteria, Cloacibacterium spp., in the most abundant and active phylum Bacteroioda, were likely major N2O sinks. Elevated dissolved oxygen (DO) concentration inhibited clade II nosZ expression but not nrfA expression, potentially switching phenotypes from N2O reduction to ammonification. Collectively, the multi-omics analysis illuminated vital bacteria responsible for N2O reduction and ammonification in microaerophilic and aerobic conditions, facilitating high-performance ammonia recovery.

ecology↗

Direct genome sequencing of respiratory viruses from low viral load clinical specimens using target capture sequencing technology

The use of metagenomic next-generation sequencing technology to obtain complete viral genome sequences directly from clinical samples with low viral load remains challenging--especially in the case of respiratory viruses--due to the low copy number of viral versus host genomes. To overcome this limitation, target capture sequencing for the enrichment of specific genomes has been developed and applied for direct genome sequencing of viruses. However, as the efficiency of enrichment varies depending on the probes, the type of clinical sample, etc., validation is essential before target capture sequencing can be applied to clinical diagnostics. Here we evaluated the utility of target capture sequencing with a comprehensive viral probe panel for clinical respiratory specimens collected from patients diagnosed with SARS-CoV-2 or influenza type A. We focused on clinical specimens containing low copy numbers of viral genomes. Target capture sequencing yielded approximately 180- and 2000-fold higher read counts of SARS-CoV-2 and influenza A virus, respectively, than metagenomic sequencing when the RNA extracted from specimens contained 59.3 copies/{micro}L of SARS-CoV-2 or 544 copies/{micro}L of influenza A virus, respectively. In addition, the target capture sequencing identified sequence reads in all SARS-CoV-2- or influenza type A-positive specimens with <26 RNA copies/{micro}L, some of which also yielded >70% of the full-length genomes of SARS-CoV-2 or influenza A virus. Furthermore, the target capture sequencing using comprehensive probes identified co-infections with viruses other than SARS-CoV-2, suggesting that this approach will not only detect a wide range of viruses, but also contribute to epidemiological studies.

genomics↗

Two doses of mRNA vaccine elicit cross-neutralizing memory B-cells against SARS-CoV-2 Omicron variant

SARS-CoV-2 Beta and Omicron variants have multiple mutations in the receptor-binding domain (RBD) allowing antibody evasion. Despite the resistance to circulating antibodies in those who received two doses of mRNA vaccine, the third dose prominently recalls cross-neutralizing antibodies with expanded breadth to these variants. Herein, we longitudinally profiled the cellular composition of persistent memory B-cell subsets and their antibody reactivity against these variants following the second vaccine dose. The vaccination elicited a memory B-cell subset with resting phenotype that dominated the other subsets at 4.9 months. Notably, most of the resting memory subset retained the ability to bind the Beta variant, and the memory-derived antibodies cross-neutralized the Beta and Omicron variants at frequencies of 59% and 29%, respectively. The preservation of cross-neutralizing antibody repertoires in the durable memory B-cell subset likely contributes to the prominent recall of cross-neutralizing antibodies following the third dose of the vaccine. One Sentence SummaryFully vaccinated individuals preserve cross-neutralizing memory B-cells against the SARS-CoV-2 Omicron variant.

immunology↗