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At least 19 recordsLinked to original sources
PubMed2025

Parallel algorithms for phylogenetic inference under a structured coalescent approximation.

While advances in molecular epidemiology and computational modeling have enhanced our capacity to track pathogen evolution, the accurate reconstruction of spatiotemporal transmission dynamics remains essential for developing epidemic preparedness frameworks and implementing outbreak response measures. Structured coalescent models offer a phylogeographic framework by restricting lineage coalescence events to geographically proximate host populations. Although the Bayesian structured coalescent approximation (BASTA) provides a tractable approach, contemporary phylogeographic analyses involving dozens of geographic localities and hundreds to thousands of viral genomes substantially exceed the computational capacity of existing implementations. The BASTA likelihood scales cubically with deme count and quadratically with sequence count due to matrix exponentiation and pairwise coalescent probability calculations. Here, we introduce a comprehensive algorithmic restructuring of the structured coalescent likelihood that eliminates redundancies, optimizes memory access, and exposes parallelization opportunities. Our approach reorganizes computations along three dimensions: (i) independent calculation of deme-transition probability matrices across time intervals; (ii) simultaneous evaluation of partial likelihood vectors within temporal slices; and (iii) concurrent aggregation of coalescent probabilities. Algorithmic restructuring cuts average coalescent likelihood computation by 7-8 fold, and parallelization further boosts performance to 10-26 fold, enabling joint phylogeographic analyses of dengue virus across 10 South American countries and H5N1 avian influenza across 20 Eurasian regions to finish in a fraction of prior time. This computational efficiency also enables comparison between backward-in-time structured coalescent approximations and forward-in-time phylogeographic methods, revealing that the former provides appropriately conservative posterior estimates, particularly at intermediate phylogenetic depths. We integrate our implementation into the popular BEAST X and BEAGLE software packages, with an accompanying interface in BEAUti X to easily set up the analyses, providing researchers with an accessible and scalable tool for real-time phylogeographic surveillance of rapidly evolving pathogens.

Journal Article↗
PubMed2025

Bayesian Inference of Pathogen Phylogeography using the Structured Coalescent Model.

Over the past decade, pathogen genome sequencing has become well established as a powerful approach to study infectious disease epidemiology. In particular, when multiple genomes are available from several geographical locations, comparing them is informative about the relative size of the local pathogen populations as well as past migration rates and events between locations. The structured coalescent model has a long history of being used as the underlying process for such phylogeographic analysis. However, the computational cost of using this model does not scale well to the large number of genomes frequently analysed in pathogen genomic epidemiology studies. Several approximations of the structured coalescent model have been proposed, but their effects are difficult to predict. Here we show how the exact structured coalescent model can be used to analyse a precomputed dated phylogeny, in order to perform Bayesian inference on the past migration history, the effective population sizes in each location, and the directed migration rates from any location to another. We describe an efficient reversible jump Markov Chain Monte Carlo scheme which is implemented in a new R package StructCoalescent. We use simulations to demonstrate the scalability and correctness of our method and to compare it with existing software. We also applied our new method to several state-of-the-art datasets on the population structure of real pathogens to showcase the relevance of our method to current data scales and research questions.

Bayes Theorem↗
PubMed1979

Why do crystalline precipitates in plasma cells always coalesce with parallel light and dark lines strictly end-to-end and side-to-side?

During transmission electron microscopy of plasma cells from two patients with plasma cell proliferative disorders, we observed a large number of small crystals, most of which showed a striation with alternating light and dark parallel lines. Ultraphotos strongly suggested that smaller crystals often coalesced to larger ones. The coalescence occurred in such a way that the parallel lines of the respective smaller crystals always met each other end-to-end and hardly ever end-to-side. A similar pattern can be seen on previously published ultraphotos from other patients with plasma cell proliferative disorders and intracellular crystals, although not commented upon by the respective authors. The parallel lines of the smaller crystals certainly must correspond to defined structures of the crystal. The stability of a certain configuration is therefore in all likelihood due to electrical potentials created by the crystal structure.

Crystallization↗
PubMed2026

Maintenance of nucleosome organization through replication and transcription counteracts aberrant coalescence of active chromatin.

Nucleosomes with their associated modifications organize and regulate the genome. It is unclear how this is integrated with the requirement of replication and transcription to access the DNA template without jeopardizing chromatin function. Here, we reveal a unified requirement for the histone chaperone FACT in mediating nucleosome disruption and reassembly during mammalian replication and transcription. Upon acute FACT depletion, replisome and RNA polymerase progression is halted genome wide, and chromatin structure in their wake collapses, with reduced nucleosome occupancy, irregular spacing, and intermediate assemblies. Chromatin states deteriorate as modified histones are lost due to a lack of histone recycling. Chromatin fiber disorder further manifests in the 3D genome, triggering active genes to coalesce in aberrant microcompartments. Similarly, aberrant compartments form in cells failing to maintain chromatin fiber structure through replication. Nucleosome organization therefore dynamically regulates genome architecture, guarding against spurious chromatin aggregation.

Nucleosomes↗
PubMed2025

Coalescing single-cell genomes and transcriptomes to decode breast cancer progression.

Understanding epithelial lineages of breast cancer and genotype-phenotype relationships requires direct measurements of the genome and transcriptome of the same single cells at scale. To achieve this, we developed wellDR-seq, a high-genomic-resolution, high-throughput method to simultaneously profile the genome and transcriptome of thousands of single cells. We profiled 33,646 single cells from 12 estrogen-receptor-positive breast cancers and identified ancestral subclones in multiple patients that showed a luminal hormone-responsive lineage, indicating a potential cell of origin. In contrast to bulk studies, wellDR-seq enabled the study of subclone-level gene-dosage relationships, which showed near-linear correlations in large chromosomal segments and extensive variation at the single-gene level. We identified dosage-sensitive and dosage-insensitive genes, including many breast cancer genes as well as sporadic copy-number aberrations in non-cancer cells. Overall, these data reveal complex relationships between copy number and gene expression in single cells, improving our understanding of breast cancer progression.

Breast Neoplasms↗
PubMed2025

A General Framework for Branch Length Estimation in Ancestral Recombination Graphs.

Inference of Ancestral Recombination Graphs (ARGs) is of central interest in the analysis of genomic variation. ARGs can be specified in terms of topologies and coalescence times. The coalescence times are usually estimated using an informative prior derived from coalescent theory, but this may generate biased estimates and can also complicate downstream inferences based on ARGs. Here we introduce, POLEGON, a novel approach for estimating branch lengths for ARGs which uses an uninformative prior. Using extensive simulations, we show that this method provides improved estimates of coalescence times and lead to more accurate inferences of effective population sizes under a wide range of demographic assumptions (population expansion, bottleneck, split, etc). It also improves other downstream inferences including estimates of mutation rates. We apply the method to data from the 1000 Genomes Project to investigate population size histories and differential mutation signatures across populations. We also estimate coalescence times in the HLA region, and show that they exceed 30 million years in multiple segments.

Ancestral Recombination Graph↗
PubMed2025

Temporal reconstruction of a Salmonella Enteritidis ST11 outbreak in New Zealand.

Outbreaks caused by Salmonella Enteritidis are commonly linked to eggs and poultry meat internationally, but this serovar had never been detected in Aotearoa New Zealand (NZ) poultry prior to 2021. Locally designated genomic cluster Salmonella Enteritidis_2019_C_01, was implicated in a 2019 outbreak associated with a restaurant in Auckland. Four Enteritidis_2019_C_01 sub-clusters have since been identified, two retrospectively, in the Auckland region. Authorities initiated a formal outbreak investigation after genomically indistinguishable S. Enteritidis was isolated from the NZ poultry production environment. This study analysed 231 S. Enteritidis genomes obtained from the outbreak using Bayesian phylodynamic tools to gain insight into the outbreak's dynamics and origin. We used Bayesian integrated coalescent epoch plots to estimate the change of the Enteritidis ST11 population size over time and marginal structured coalescent approximation to estimate transmission between poultry producers. We investigated human and poultry isolates to elucidate the time and location of the most recent common ancestor of the outbreak and transmission pathways. The median most recent common ancestor was estimated to be February 2019. We found evidence of amplification and spread of strain Enteritidis_2019_C_01 within the poultry industry, as well as transmission events throughout the production chain. The intervention by the public health and food safety authorities coincided with a drop in the effective population size of the S. Enteritidis ST11 as well as notified human cases. This information is crucial for understanding and preventing the transmission of S. Enteritidis in NZ poultry to ensure poultry meat and eggs are safe for consumption.

Salmonella enteritidis↗
PubMed1979

Ultrastructure and cytochemistry study of the yolk syncytial layer in the alevin of trout (Salmo fario trutta L.) after hatching. I. The vitellolysis zone.

After hatching, the yolk syncytial layer of Salmo fario trutta may be subdivided into two zones, namely, the vitellolysis zone (containing numerous yolk platelets), and the cytoplasmic zone (where yolk platelets are rare). In the vitellolysis zone, two stages in the utilization of the yolk are observed: 1) The first stage, comprises the formation of yolk platelets from coalescent yolk by spherical cutting out and basal scission. This process seems to be achieved by the invagination of fibrillar elements into the coalescent yolk to form individual yolk platelets surrounded by a limiting membrane. 2) The second stage essentially consists of the extrusion or budding of yolk matter from a yolk platelet. Again, where the yolk matter leaves a platelet, fibrillar elements are evident and show an alkaline phosphatase activity. The platelets of the vitellolysis zone have a homogeneous content and variable diameter; they never acquire a heterogeneous and polymorphic aspect which could be interpreted as an intermediate stage in their degradation.

Acid Phosphatase↗
PubMed2026

Cytonuclear conflict and reticulate evolution in the Morelloid clade (Solanum, Solanaceae): Insights from genome skimming and network Phylogenomics.

The Morelloid clade (black nightshades) is one of the most strongly supported clades within the megadiverse Solanum genus. It comprises 76 globally distributed, non-spiny herbaceous and suffrutescent species. While often erroneously considered poisonous weeds, several species are economically important as orphan crops. The clade is closely related to tomato and potato but, due to a lack of focused breeding efforts, remains a putative reservoir of genetic diversity for crop improvement. Despite this potential, we lack fundamental knowledge on the evolution of the Morelloid clade. The group includes polyploid species with unknown parental origins-likely reflecting reticulate processes such as hybridization, introgression, and associated backcrossing events. Prior analyses have been unable to disentangle these processes, leaving the mechanisms underlying reticulate evolution in the Morelloid clade poorly understood. Here, we use genome skimming to produce a well-supported maximum likelihood plastid phylogeny from complete circularized plastomes and a coalescent-based species tree from combined Angiosperms353 and conserved ortholog set nuclear markers. Our dataset, composed of previously published data and deep genome skimming from herbarium samples, spans 26 Morelloid species. To investigate phylogenetic discordance, we used a nuclear phylogenetic network, multispecies coalescent simulations, a fused rooted nuclear chloroplast tree, and quantification of nuclear gene tree concordance. We show that incongruence between nuclear and plastid trees is pervasive and cannot be explained by incomplete lineage sorting alone. Instead, our results demonstrate that events consistent with repeated chloroplast capture have shaped the reticulate evolutionary history of the clade, especially among African polyploid and Pan-American diploid lineages.

Phylogeny↗
PubMed2026

Nuclear single-copy orthologous genes as phylogenomic markers for resolving the closely related firefly genera Pteroptyx, Medeopteryx, and Trisinuata (Coleoptera: Lampyridae: Luciolinae).

Fireflies (Lampyridae) are bioluminescent beetles with broad ecological roles across temperate and tropical ecosystems, occupying diverse habitats including forests, wetlands, grasslands, mangroves, and riverine systems. The subfamily Luciolinae is primarily distributed across Asia and the Indo-Pacific. Phylogenetic relationships among three closely related Luciolinae genera - Medeopteryx, Pteroptyx, and Trisinuata - remain unresolved using mitochondrial genome data alone. This study used nuclear genome data to resolve relationships among these genera and identify a lighter-weight nuclear marker panel for expanding taxon sampling. Draft genomes were reconstructed for fifteen firefly species, eight from the focal genera, and analyzed with five published firefly genomes. Using BUSCO and OrthoFinder, 1,011 nuclear single-copy orthologs (SCOs) were identified for phylogenomic inference. Discordance between concatenation- and coalescence-based phylogenies indicated incomplete lineage sorting (ILS). The coalescence-based phylogeny recoveredPteroptyxas monophyletic and sister to a (Medeopteryx,Trisinuata) clade, with Trisinuata nested within a non-monophyletic Medeopteryx; however, quartet support at the base of Pteroptyx, particularly at Pt. valida, was low.Filtering for compositional homogeneity, clock-likeness, and species-tree concordance yielded 103 SCOs with a significantly higher proportion of parsimony-informative sites than non-selected loci, retaining the backbone topology with higher gene concordance support at scored clades, while ILS-driven discordance at Pt. valida persists - confirming that the reduced panel retains phylogenetic resolving power for future taxon sampling. These findings demonstrate a practical framework for using nuclear SCOs to resolve close phylogenetic relationships within Luciolinae. Future work should expand taxon sampling - especially forTrisinuata - alongside long-read assemblies, for a more robust phylogenomic framework.

Fireflies↗
PubMed1977

Effect of zinc deficiency on intestinal transport triglyceride in the rat.

Ultrastructural and biochemical changes in the intestinal epithelium during the process of active triglyceride absorption were studied in rats fed a zinc-deficient diet as compared with those of pair-fed and ad libitum-fed zinc-supplemented controls. The rate of triglyceride absorption markedly decreased in zinc-deficient rats. Despite a significant reduction in pancreatic lipase activity, the digestion of triglycerides proceeded normally in the zinc deficient rats, as evidenced by no apparent signs of diarrhea (or steatorrhea) and by the appearance of the hydrolytic products such as free-fatty acids and monoglycerides in the intestinal mucosa. The mucosa uptake of digested lipids and resynthesis of triglycerides in the mucosa from deficient rats were normal. Ultrastructural and chromatographic analysis of the mucosal lipids indicated a massive accumulation of lipid droplets, predominantly in the form of triglycerides. The primary defect in lipid absorptive processes in zinc-deficient rats occurred in the formation of chylomicrons. The lipid droplets in the mucosa of deficient rats were physically unstable. This instability was shown by coalescence of droplets which did not appear to be membrane-bound. Coalescing lipid droplets ranged from 2.0 to 4.0 micron in diameter. The absorptive cells were not able to discharge lipid droplets of this size into the intercellular spaces and hence into the lamina propria, resulting in the accumulation of the large droplets within the mucosa. This exit block to the movement of lipid droplets out of the mucosal cell appeared to be due to the failure, in zinc-deficiency, of the mucosal synthesis of proteins required for the formation of chylomicrons. Ultrastructural observations demonstrated changes in the subcellular organelles related to protein synthesis, including a marked reduction in granular endoplasmic reticulum and a quiescent appearance of the Golgi-complex.

Animals↗
PubMed1976

Electron microscopic observations of "keratin pools" in chronic hyperplastic oral mucosa.

"Keratin pools," previously characterized clinically and histochemically in the superficial epithelium of chronic hyperplastic oral mucosa, were studied by light and electron microscopy. These occured as small beaded and larger coalescent masses which varied in metachromasia. Ultrastructurally, the "keratin pools" consisted of electron-dense, amorphous or finely-granular material developing and coalescing, chiefly as extracellular deposits. The "pools" frequently possessed a layered arrangement alternating with cells having distinct tonofilaments, desmosomes, and definite cell membranes. Occasional bands of filamentous-like material, possibly representing tonofilament bundles, were observed in some "pools."

Aged↗
PubMedDate not supplied

Acute mastoiditis and cholesteatoma.

Acute coalescent mastoiditis is an uncommon sequela of acute otitis media. It occurs principally in the well-pneumatized temporal bone. The findings of fever, pain, postauricular swelling, and otorrhea are classic. Cholesteatoma, on the other hand, being associated with chronic infection, usually occurs in the sclerotic temporal bone. The signs and symptoms are isidious in nature and consist of chronic discharge and hearing loss which result from its mass, bone erosion, and secondary infection. Of 17 consecutive cases of acute mastoiditis over a six-year period, four were atypical because they were complications of chronic otitis media and cholesteatoma, yet they had the physical findings of acute mastoiditis-subperiosteal abscess and purulent otorrhea, plus radiographic evidence of mastoid coalescence.

Acute Disease↗
PubMed1978

The packaging unit: a basic structural feature for the condensation of late cricket spermatid nuclei.

The alignment, folding and packaging of cricket chromatin was examined during late spermiogenesis by an electron-microscope study of nuclei dispersed by air--liquid surface tension forces after detergent treatment. Late developing spermatid genomes arrange themselves in multiple packaging units in a stepwise process which includes: (1) a loss of the beaded repeating structure of chromatin as nucleoprotein fibres become smooth and gradually assume a uniform diameter; (2) a side-by--side alignment of structurally modified chromatin fibres; and (3) a regular folding into packaging units. Alignment and folding of chromatin fibres are presumably mediated by intermolecular bonds easily disrupted by spreading forces. In very late spermatids, interfibre binding forces are difficult to overrride by spreading alone, indicating a stronger cross-linking of increasingly coalescent packaging units. 'Unit to unit' coalescence stabilizes the nuclear structure, first limiting and afterwards denying penetration of phosphotungstic acid, as displayed in thin sections of extremely cricket spermatid nuclei. Binding of phosphotungstate by nuclear basic proteins can be facilitated by limited protein solubilization after disulphide reduction of unfixed cricket tests with sodium dodecyl sulphate and dithiothreitol. Results of this study permit the proposal of model experiments useful for clarifying the organization of highly condensed spermatid genomes and for evaluating the structure of genome segments in systems wherein changes of chromatin-associated protein occur.

Animals↗
PubMed1978

Electron microscopic studies on pulmonary alveolar microlithiasis.

The lung tissue of pulmonary alveolar microlithiasis was studied morphologically. Scanning electron microscopy revealed that the microliths were globular or irregular in shape or lobulated and in some loci were coalesced. The outer surface was granular or rough accompanied with deposits. The internal structures consisted of concentric laminar deposits. Frequently, two or more laminar structures were found on one cut surface. These findings may imply that the microliths grow by surface deposition and may coalesce during early stages of formation. In a high power view, granules were seen on the surface. Numerous scale-like structures and elongated electron-dense bodies inside the microliths were other peculiar findings of scanning and transmission electron microscopic studies, respectively. Elastosis in the alveolar interstitium and deposition of abundant glycogen granules in the bronchiolar epithelial cells were the notable findings of transmission electron microscopy.

Adult↗