Biology subjects

Pollock, D.

Publications and source records attributed to Pollock, D..

6 recordsLinked to original sources

bioRxiv2026

Population genomics reveals multi-scale mechanisms sustaining schistosomiasis re-emergence in a near-elimination setting

In China, sustained snail control, environmental management, and mass drug administration with praziquantel reduced schistosomiasis to near-elimination levels, yet re-emergence in Sichuan Province during the early 2000s exposed vulnerabilities in late-stage control. We conducted a novel investigation of Schistosoma japonicum re-emergence in Sichuan in order to identify the processes underlying re-emergence and to showcase how genomic data can be used in such investigations. We sequenced whole genomes from 270 miracidia collected from 53 human hosts across 17 villages in 2007 - the year after re-emergence was documented. Population genomic analyses revealed a broadly cohesive regional parasite population with weak geographic structuring. Genome-wide diversity was substantial, and demographic reconstructions revealed no recent decline in effective population size, demonstrating that parasite populations were not demographically fragmented at the onset of re-emergence, hinting at maintenance in reservoir populations. At finer spatial scales, several villages exhibited low diversity and elevated inbreeding, consistent with localized transmission maintained by small founding populations. Estimates of pairwise genetic relatedness revealed dense within-village sibling clusters alongside second- and third-degree relationships spanning villages, and rare first- and second-degree cross-village links. These findings are consistent with highly focal transmission with episodic parasite dispersal across villages, leading to a regional transmission network. Inferred minimum worm burden across hosts varied from 1 to 11 adult worm pairs, indicating heterogeneity in within-host parasite diversity, although uneven sampling limited inference. Together, these findings indicate that schistosomiasis re-emergence in this near-elimination setting was likely facilitated by a diverse parasite population maintained in reservoir populations, and that transmission, while predominantly local was occurring across a network of connected villages. This work illustrates how population genomics can reveal mechanisms driving re-emergence in late-stage elimination in complex, multi-host transmission systems. Author SummarySchistosomiasis is a parasitic disease that affects millions of people worldwide. Understanding the factors that contribute to persistence and transmission, even in the face of control programs, is central to reducing and ultimately eliminating the disease. In China, decades of intensive control efforts have dramatically reduced infections, yet the disease continued to persist in some regions. In this study, we analyzed the genomes of 270 parasite larvae collected from infected humans across 17 villages in Sichuan Province, China, shortly after schistosomiasis re-emerged in the region. By examining genetic relationships among parasites, we reconstructed patterns of transmission across villages and within individual infections. Our findings suggest that, despite major reductions in human infection prevalence, parasite populations sizes do not show signatures of recent population decline, indicating that non-human hosts may serve as key reservoirs promoting persistence. We also find that local transmission pathways, including clonal infections infecting multiple humans derived from a relatively small number of snail hosts, maintain parasite transmission pathways. Collectively, these findings suggest non-human hosts, intact local transmission pathways, and regional connectivity together enabled re-emergence, highlighting important challenges for elimination programs

genomics↗

bioRxiv2025

Sampling Microbial Dynamics in the Salish Sea Estuary: Evaluating Methods to Capture Cyanobacteria and Cyanophage

Picocyanobacteria from the genera Prochlorococcus and Synechococcus thrive across the globe in aqueous environments, have relatively small genomes, and have growth dynamics regulated by both viral interactions and abiotic conditions, making them excellent model organisms for exploring host-pathogen coevolution. The Salish Sea, located in the Western coastal waters bordering the USA and Canada, is at the current northern boundary (defined by Prochlorococcus versus Synechococcus prevalence ratios) of the range of Prochlorococcus. Predictions suggest that this boundary will shift northward as warmer waters move northward, providing an excellent system to study host-pathogen dynamics and coevolution in a changing environmental context. In preparation for such studies, we developed and refined methods to sample and sequence cyanobacteria, cyanophages, and their abiotic environment. In addition to basic methodological questions focused on the physical sampling, filtering, viral precipitation, DNA extraction, and technical replicability, we explored how well our filtering and extraction protocols enrich for our main target, picocyanobacteria. The protocol described herein can successfully discriminate large-cell eukaryotic organisms, but size fractionation of picocyanobacteria appears to be affected by the presence of free DNA, multicellular structures, and abundant tycheposons. Our preferred final protocol at the conclusion of these experiments based on yield and processing time is presented. We recovered substantial Prochlorococcus, Synechococcus and amoeba-like sequences in most samples, and preliminary exploration of relative taxon sequence read recoveries across locations, over time, and tidal conditions are also discussed. Approaches described here may be useful to other efforts such as harmful algal bloom monitoring, species isolation and enrichment, water quality assessments, anti-viral discovery, and understanding picocyanobacterial population changes over space and time.

microbiology↗

bioRxiv2025

ProteoMeter: A pipeline for integrating multi-PTM and limited proteolysis data to reveal modification-structure coupling at the residue level

Systemic perturbations trigger extensive changes across the proteome-altering protein abundance, post-translational modifications (PTMs), conformational states, and complex assembly. Interpreting these effects demands computational pipelines capable of integrating diverse proteomics modalities, such as multi-PTM profiling, limited proteolysis mass spectrometry (LiP-MS), and cross-linking mass spectrometry (XL-MS), within a unified and interoperable framework. Because instrument data are quantified at the peptide level, mapping these measurements to individual residue or modification site is essential for biologically meaningful interpretation. We introduce ProteoMeter, an open-source Python library designed to integrate multi-modal proteomics datasets and map them to single-residue resolution using a standardized coordinate framework. We showcase its capabilities in a combined multi-PTM and LiP-MS analysis profiling the proteomic response to human coronavirus 229e (HCoV-229E) infection.ProteoMeteris actively maintained and is freely available-including all source code and figure-generation scripts-at the following repository: https://github.com/PNNL-Predictive-Phenomics/ProteoMeter.

systems biology↗

bioRxiv2025

Genetically encoded nAChR upregulation is neuroprotective in female parkinsonian mice

Parkinsons disease is projected to rise to pandemic proportions by 2050, which has resulted in an urgent need for disease-modifying treatments. In this regard, we previously showed that in a mouse model of parkinsonism with unilateral 6-hydroxydopamine (6-OHDA) injection into the dorsolateral striatum (DLS), low doses of the neuronal nicotinic acetylcholine receptor (nAChR) partial agonist and smoking cessation drug, cytisine exerts sex-specific neuroprotection in substantia nigra pars compacta (SNc) dopaminergic (DA) neurons of only female mice by reducing apoptotic endoplasmic reticulum (ER) stress. Although these data suggest that neuroprotection might occur via cytisine-mediated upregulation of {beta}2 subunit-containing ({beta}2*) nAChRs in SNc DA neurons, there is no direct evidence to support this idea. Therefore, this study asks the critical question of whether upregulation of {beta}2* nAChRs in SNc DA neurons alone is sufficient to reduce apoptotic ER stress and exert neuroprotection in a preclinical unilateral DLS mouse model of 6-OHDA-induced parkinsonism. To address this question, we generate and characterize a novel {beta}2-upregulated transgenic mouse line. These transgenic mice possess mutations in the M3-M4 intracytoplasmic loop of {beta}2 subunits that cause constitutive upregulation of {beta}2* nAChRs without nicotinic ligands. Surprisingly, when compared to wild-type littermates, only female {beta}2-upregulated transgenic mice demonstrate upregulation of {beta}2* nAChRs in SNc DA neurons as assessed by significant increases in Sec24D-containing ER exit sites (Sec24D-ERES). Using the optogenetic calcium and dopamine sensors, GCaMP6f and GRABDA respectively, we found significant increases in dihydro-beta-erythroidine (Dh{beta}E)-sensitive {beta}2* nAChR-mediated calcium influx in SNc DA neuron dendrites and Dh{beta}E-sensitive acetylcholine (ACh)-evoked dopamine release at SNc DA neuron terminals of the DLS in female transgenic mice. We then used four independent readouts to assess neuroprotection of SNc DA neurons following unilateral 6-OHDA injection into the DLS, viz., contralateral apomorphine-induced rotations, preservation of SNc DA neurons, inhibition of a major proapoptotic ER stress protein, C/EBP homologous protein (CHOP) and glial fibrillary acid protein (GFAP) expression in SNc astrocytes. In all four readouts, female {beta}2-upregulated transgenic mice showed significant neuroprotection. From a clinical perspective, this study shows that upregulation without nicotinic ligand-mediated activation of {beta}2* nAChRs in SNc DA neurons can be a translationally viable disease-modifying strategy for Parkinsons disease. In addition, we envision that the novel transgenic {beta}2-upregulated mice created in this study will provide a valuable tool for understanding the role of nAChR upregulation in major neurological disorders such as addiction, anxiety, depression and dementia.

neuroscience↗

bioRxiv2018

Markov katana: a novel method for Bayesian resampling of parameter space applied to phylogenetic trees

Phylogenetic inference requires a means to search phylogenetic tree space. This is usually achieved using progressive algorithms that propose and test small alterations in the current tree topology and branch lengths. Current programs search tree topology space using branch-swapping algorithms, but proposals do not discriminate well between swaps likely to succeed or fail. When applied to datasets with many taxa, the huge number of possible topologies slows these programs dramatically. To overcome this, we developed a statistical approach for proposal generation in Bayesian analysis, and evaluated its applicability for the problem of searching phylogenetic tree space. The general idea of the approach, which we call Markov katana, is to make proposals based on a heuristic algorithm using bootstrapped subsets of the data. Such proposals induce an unintended sampling distribution that must be determined and removed to generate posterior estimates, but the cost of this extra step can in principle be small compared to the added value of more efficient parameter exploration in Markov chain Monte Carlo analyses. Our prototype application uses the simple neighbor-joining distance heuristic on data subsets to propose new reasonably likely phylogenetic trees (including topologies and branch lengths). The evolutionary model used to generate distances in our prototype was far simpler than the more complex model used to evaluate the likelihood of phylogenies based on the full dataset. This prototype implementation indicates that the Markov katana approach could be easily incorporated into existing phylogenetic search programs and may prove a useful alternative in conjunction with existing methods. The general features of this statistical approach may also prove useful in disciplines other than phylogenetics. We demonstrate that this method can be used to efficiently estimate a Bayesian posterior.

evolutionary biology↗

bioRxiv2016

Strong and Fluctuating Sequence Constraints Drive Alu Evolution

Though Alu elements are the most common and well-studied transposable elements in the primate genome, Alu evolutionary dynamics remain poorly understood. To better understand these dynamics, we improved our recently introduced Bayesian transposable element ancestral reconstruction method to incorporate automated alignment and be more computationally efficient. We then used it to reconstruct the relationships among almost 800,000 Alu elements in the human genome. We identified the phylogenetic network relating 154 ancestral replicative Alu sequences, and found that the aligned ancestors vary at only 56 out of ~300 sites. We show that the limited number of variable sites among replicative Alu ancestors is best explained by strong sequence constraints on Alu replicative capacity. Moreover, the pattern of variation suggests that sequence constraints fluctuated over the course of Alu evolution, driving the extinction of older Alu subfamilies and the birth of newer ones. Previous analyses have taken the tight clustering of Alu sequences with age as evidence that all Alu sequences are descended from a small number of \"master elements.\" Our results imply instead that the clustering of Alu sequences with age results from fluctuating sequence constraints, and that there were over 4,000 replicative loci during the course of Alu evolution, most of which were disabled by mutation before mutating to new replicative sequences. We also predict which sites have been functionally important for replication, and how these sites have changed over time. The newly clarified dynamics of Alu evolution invalidate assumptions used in common method of transposable element classification and phylogenetics.\n\nSignificance StatementTransposable elements are genomic sequences that can insert copies of themselves elsewhere in the genome. Alu is the most abundant transposable element in primates, making up 10% of the human genome. Due to its ubiquity and tendency to cause genomic instability, Alu has played a major role in shaping primate genomes. Characterizing the trajectory of Alu evolution is important for understanding how the human genome evolved.\n\nPrevious analyses of Alu concluded that a tiny number of elements generated all copies, and existing classifications of Alu reflect that conclusion. In a whole-genome analysis, we determine that many more elements were replicative than previously understood, indicating that current classifications of Alu are flawed. We develop an alternative reconstruction of Alu evolutionary history.

genomics↗