Biology subjects

Chen, Z.

Publications and source records attributed to Chen, Z..

At least 181 records · Page 10Linked to original sources

bioRxiv2025

Structural basis of asymmetric transcription through a composite nucleosome formed by a hexasome and an octasome

The overlapping dinucleosome (OLDN), a composite chromatin particle consisting of a hexasome and a canonical octasome, forms immediately downstream of transcription start sites, likely through chromatin remodeling activity, and has been proposed to act as a transient regulatory intermediate during transcription. However, how RNA polymerase II (RNAPII) engages with and transcribes through this unusual structure remains unclear. Here, we reconstituted OLDNs in vitro and performed transcription assays with RNAPII. We found that transcription efficiency was markedly higher when RNAPII initiated from the hexasome side than from the octasome side. Cryo-electron microscopy further revealed that transcription from the hexasome side induced pronounced conformational rearrangements, in which RNAPII progression dramatically opened the hexasome-octasome interface. These results uncover the mechanism by which RNAPII senses the intrinsic transcriptional polarity of OLDNs and suggest that OLDNs function as dynamic, directionally sensitive regulators of transcription elongation.

molecular biology↗

bioRxiv2025

Plasma Induced Afterglow Luminescence

Afterglow imaging, is an emerging optical modality using agents that emit persistent luminescence after excitation ceases to eliminate tissue auto fluorescence and improve signal-to-background ratios. However, there was limited number of organic matters could produce persistent luminescence when using light, ultrasound or ionizing radiation as the excitation source. Herein, we explored cold atmospheric plasma (CAP) as a universal and exclusive stimulus for activating intense and long-lasting afterglow from widely-exist organic matters, which could not easily excited by light, ultrasound or X-ray radiation. Furthermore, we demonstrated the biomedical applications of the CAP-induced long-lasting afterglow for photodynamic residual removal after surgical resection of tumor. It should be point out that using CAP as the excitation source might opened new avenue for afterglow imaging clinical translation based on some FDA-approval organic matters learning from the drug repurposing strategy.

biochemistry↗

bioRxiv2025

Mapping Core Components of Membrane-less Organelles in Living Cells by Phase-APEX2 Proximity Labeling

Membrane-less organelles (MLOs), formed via liquid-liquid phase separation, are crucial for organization of biomacromolecules and cellular processes, yet their dynamic nature challenges compositional analysis. Conventional proximity labeling methods lack the specificity to overcome high background and systematic biases inherent in studying these condensates. Here we introduce Phase-APEX2, a three-input AND-gate strategy that dramatically enhances labeling specificity. By integrating a split-APEX2 system with a light-controlled H2O2 generator, we developed Phase-APEX2 platforms for two application contexts: Phase-APEX2-MS for proteomics and Phase-APEX2-seq for genomics. Our analyses revealed not only the core interactomes of the nucleolus and stress granules with high accuracy but also uncovered distinct "molecular grammars" governing their assembly and a surprising link between nucleolar dynamics and the transcriptional regulation of mitosis-related genes. This highly specific and adaptable platform opens new avenues for exploring the composition and function of diverse biomolecular condensates.

cell biology↗

bioRxiv2025

TaoChongBao: A Large-Scale Caenorhabditis elegans Mutagenesis and Missense Variant Database Bridging Worm and Human Genomes

We generated and sequenced 12,069 viable Caenorhabditis elegans strains produced by ethyl methanesulfonate mutagenesis, identifying 20,315,536 variants, including 541,102 unique missense mutations across 20,914 genes. To organize and visualize this resource, we developed TaoChongBao, an open-access database and strain repository that integrates C. elegans mutation data with AlphaMissense-predicted pathogenicity scores and ClinVar clinical annotations. TaoChongBao enables users to explore worm missense variants, identify conserved residues corresponding to human pathogenic sites, and access viable strains for experimental validation. Compared with the previous Million Mutation Project in C. elegans, TaoChongBao expands mutation coverage over twenty-fold and emphasizes amino acid-altering variants. This resource provides a scalable platform for functional residuomics, variant interpretation, and comparative analyses between C. elegans and human genomes.

bioinformatics↗

bioRxiv2025

MFAP5 Drives Elastic Fiber Disorganization to Promote Pulmonary Fibrosis

BACKGROUNDElastic fibers (EF) disorganization contributes to increased tissue stiffness and impaired lung function in pulmonary fibrosis (PF). However, the complex structural features of EF are difficult to capture using conventional histology. Moreover, the molecular mechanisms governing EF homeostasis during fibrosis remain poorly understood. METHODSA high-dimensional Elastic Fiber Algorithm (EFA) was developed to digitally quantify EF structural features in PF. Gene variation-rate analysis was performed to identify candidate regulators of EF homeostasis. Fibroblast-specific and pathological fibroblast-specific MFAP5 knockout mice were generated to assess the role of MFAP5 in PF rodent models. Bulk RNA sequencing was employed to investigate MFAP5-mediated fibroblast activation and signaling pathways. RESULTSEFA revealed profound EF disorganization in fibrotic lungs, capturing various architectural alterations. Gene variation-rate analysis identified MFAP5 as a candidate regulator of EF homeostasis, with upregulated expression in PF patients and mouse models. Fibroblast-specific deletion of MFAP5 significantly attenuated fibrosis, restored EF architecture, reduced collagen deposition, and improved pulmonary function in PF mouse models. MFAP5-positive fibroblasts displayed a dynamic shift toward pathological states during PF progression. Mechanistically, MFAP5 promoted fibroblast activation and ECM production via v{beta}3 integrin-mediated TGF{beta} signaling. CONCLUSIONSMFAP5 is a key orchestrator of EF remodeling and fibroblast activation in PF. Targeting MFAP5 restores EF homeostasis, reduces fibrotic severity, and represents a potential therapeutic strategy for PF.

molecular biology↗

bioRxiv2025

Pial collaterals propagate neurovascular responses across functional units

Neurovascular coupling refers to the regulation of cerebral blood flow in response to neuronal activity, a process forming the basis for multiple functional neuroimaging techniques. However, the mechanisms that coordinate neurovascular responses across distinct cortical arterial territories remain poorly understood. Here we show that pial collaterals, arterio-arterial connections traditionally considered dormant under physiological conditions, serve as active conduits that propagate neurovascular signals between adjacent cortical territories and functional units. We demonstrate that neuronal activity in the somatosensory cortex triggers direct vascular signaling via endothelial Kir2.1 channels through pial collaterals, synchronizing blood flow responses beyond the activated area. The loss of pial collaterals abolished inter-territorial coupling without affecting local neurovascular responses. These results reveal that pial collaterals are critical regulators of cerebral perfusion.

neuroscience↗

bioRxiv2025

EMCF ecosystem: Towards pretrained foundation model for electron microscopy image analysis

Volume electron microscopy (vEM) enables nanoscale visualization of three-dimensional (3D) cellular ultrastructure, providing critical insights into physiological processes and pathological alterations. However, its application to large-scale biological tissues remains constrained by two major bottlenecks: prolonged image acquisition and inefficient data processing. Here, we present EMCF ecosystem (EMCFsys), an integrated ecosystem designed to overcome these challenges through three key components: a large-scale benchmark dataset (EMCFD) comprising 4,002,802 high-quality images across 14 EM modalities and 6 biological kingdoms; a foundation image restoration model (EMCellFiner); and a scalable image analysis foundation model (EMCellFound). Together, these modules systematically enhance image quality and substantially improve analysis efficiency. Our results show that EMCellFiner outperforms specialist models in restoring degraded images, even surpassing original ground truth sharpness in certain artifact regions, and reduces imaging time by 16-fold by enabling low-resolution and low dwell time acquisition. EMCellFound exhibits exceptional feature discriminability, outperforms specialist models in classification, semantic segmentation and instance segmentation. It also enables high-precision 3D reconstruction of organelles (e.g., endoplasmic reticulum) with minimal labeled data (0.01% of total volume). We validated the EMCFsys on unseen datasets across diverse biological contexts and imaging platforms. By publicly releasing both the dataset and models, we establish a scalable paradigm for automated, high-throughput vEM data interpretation, accelerating exploration of lifes nanoscale structure and function across biology.

cell biology↗

bioRxiv2025

Adenylyl cyclase 9: fundamental change of regulation in vertebrates and gene sub-functionalization after teleost-specific whole-genome duplication

Adenosine 3:5 monophosphate (cAMP) is a ubiquitous signalling molecule generated by the adenylyl cyclase family of proteins which is encoded by ten genes. The biological significance of this diversity is not well understood. In mammals, transmembrane adenylyl cyclase 9 (AC9) is resistant to regulation by heterotrimeric G proteins. A major facet of this resistance is auto-inhibition -- in the presence of activated Gs, AC9 is inhibited by its C-terminal domain. Here, we examined the natural evolution of this seemingly paradoxical control mechanism. At the primary sequence level, the hallmarks of auto-inhibition are apparent in all vertebrates, none are found in invertebrates. Teleost-specific genome duplication (TGD) resulted in adcy9 ohnologs, one of which lacked the hallmarks of auto-inhibition. This was confirmed in functional assays upon cloning and heterologous expression of the requisite cDNAs. The tissue distributions of the adcy9 ohnologs in teleost species also pointed to their sub-functionalization. Above all, auto-inhibited adcy9 was largely restricted to the brain indicating a fundamental role in brain development or function. Our findings document a quantum leap of the regulation of the enzymatic activity of AC9 in vertebrates and the potency of TGD to meet an adaptational challenge through functionally diversified ohnologs.

evolutionary biology↗

bioRxiv2025

Representation, Alignment, and Generation: A Comprehensive Survey of Foundation Models for Non-Invasive Brain Decoding

The ability to decode human thoughts, intentions, and perceptions directly from non-invasive brain recordings holds transformative potential for healthcare, communication, and human-computer interaction. However, translating the safety and scalability of methods like Functional Magnetic Resonance Imaging (fMRI), Electroencephalography (EEG), and Magnetoencephalography (MEG) into real-world utility has traditionally been hindered by low signal-to-noise ratios, limited spatial-temporal resolution, and the difficulty to collect large-scale high-quality data from an individual user. Recently, the emergence of Foundation Models (FMs)--large-scale, pre-trained architectures--has expanded the feasible operating region of non-invasive brain decoding under controlled protocols, primarily through representation learning, neuro-semantic alignment, and strong generative priors. However, evidence for robust cross-subject and real-world deployment remains uneven, as many results are still demonstrated on limited cohorts or highly controlled settings. This survey provides a comprehensive overview of how FMs are redefining the boundaries of non-invasive brain decoding. We propose a unified methodological framework that synthesizes recent advancements into a coherent process: extracting robust, transferable representations from noisy neural signals; aligning these signals with the rich semantic spaces of pre-trained vision and language models; and leveraging powerful conditional generative priors to reconstruct high-fidelity outputs. We systematically review state-of-the-art applications across three key domains: visual reconstruction, language and speech decoding, and auditory processing. Furthermore, we critically examine the persisting challenges of computational efficiency, cross-subject generalization, and privacy governance. By mapping the current landscape and identifying key gaps, this work outlines a strategic research agenda aimed at transitioning FM-driven neurotechnology from laboratory proofs-of-concept to reliable, real-world applications.

neuroscience↗

bioRxiv2025

Autoimmunity and H. pylori infection cooperatively promote epithelial tumorigenic differentiation and systemic immune modulation

Background and AimsGastric cancer (GC) demographics have shifted, with a growing impact on younger populations, particularly women. Chronic Helicobacter pylori (HP) infection is the leading risk factor for GC; however, decreasing HP prevalence means it is unlikely the cause of rising incidence of early-onset GC. Autoimmunity, which is more prevalent in women, has been proposed as a contributing factor. As autoimmunity prevalence increases, HP and gastric autoimmunity are likely to converge within one individual. This study aimed to examine how combinatorial HP infection and autoimmunity affect tumorigenesis and the immune landscape. MethodsA mouse model mimicking human CTLA4 insufficiency and its risk of autoimmunity-driven GC development, CTLA4KD, was infected with HP strain PMSS1 by oral gavage. Tumorigenesis was histologically assed. Hematopoietic and non-hematopoietic cells were analyzed using 40-color spectral flow cytometry. Human PBMCs were co-cultured with HP, followed by flow cytometry and qRT-PCR for gene expression of sorted PBMC subsets. ResultsHP infection in CTLA4KD mice advanced dysplasia and increased tertiary lymphoid structures within the gastric mucosa. Loss of E-Cadherin and DMBT1 was exacerbated in the combinatorial setting of autoimmunity and HP infection. In the innate immune system HP and autoimmunity showed an additive effect in systemic NK cell decreases. In the adaptive immune system, HP and autoimmunity cooperatively elevated the proportion of CD4+Foxp3- cells expressing the transcription factor Helios, persisting 6-8 months post infection. The Helios-expressing CD4 cells co-expressed inhibitory markers PD-1, CD200 and CD39. ConclusionAutoimmunity and HP infection cooperatively elicit long-lasting suppression of innate and adaptive immunity while promoting epithelial tumorigenic differentiation in the stomach. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=77 SRC="FIGDIR/small/690054v1_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@1096623org.highwire.dtl.DTLVardef@1099e7org.highwire.dtl.DTLVardef@1e8493forg.highwire.dtl.DTLVardef@120e5d3_HPS_FORMAT_FIGEXP M_FIG C_FIG Background and contextAutoimmunity is emerging as a contributing factor for early-onset gastric cancer especially in young women, but it is unknown how it interacts with the most prevalent etiology factor, Helicobacter pylori. New findingsThis study provides the initial evidence that Helicobacter pylori and autoimmunity cooperatively cause long-lasting suppression of innate and adaptive immunity while promoting epithelial tumorigenic differentiation in the stomach. LimitationsEven with the murine-adapted Helicobacter pylori strain PMSS1, a human pathogen, the mouse modeling remains technically and conceptually challenging and can only capture some aspects of human Helicobacter pylori infection. Clinical research relevanceThis study showcases how autoimmunity predisposed by host genetics may cooperate with a prevalent environment factor, Helicobacter pylori, to promote gastric cancer development, with cellular and histopathological changes in the stomach, as well as local and systemic alteration of immune profiles. The lasting effects long after the elimination of Helicobacter pylori suggest the necessity of remedies besides Helicobacter pylori eradication. Basic research relevanceThis study provides molecular and cellular clues for how a convergence of autoimmunity and Helicobacter pylori cooperatively downregulates tumor suppressors in gastric epithelial cells while causing long-lasting suppression of innate and adaptive immunity. More studies are needed for better understanding of the interaction between Helicobacter pylori and autoimmunity, to help develop interventions against the alarming trend of early-onset gastric cancer. Lay summaryThis study provides initial insight into how autoimmunity and Helicobacter pylori in combination may impinge on multi-pronged effect on the stomach and the immune system to accelerate gastric cancer development.

cancer biology↗

bioRxiv2025

TXNDC5 Governs Extracellular Matrix Homeostasis in Pulmonary Hypertension

BACKGROUNDPulmonary hypertension (PH) is characterized by vascular remodeling without effective treatments. Thioredoxin domain containing 5 (TXNDC5), a member of the protein disulfide isomerases (PDI) family, regulates protein folding and vascular homeostasis, yet its role in PH remains unknown. METHODSLabel-free proteomics profiled protein expression in lungs from PH patients. TXNDC5 was analyzed by single-cell RNA sequencing, immunofluorescence, and Western blot. Endothelial gain- and loss-of-function approaches were applied in Sugen5416/hypoxia (SuHx)-induced rodent PH models. RNA sequencing and protein-protein interaction analysis were used to investigate underlying mechanisms. RESULTSTXNDC5 was significantly upregulated in the lungs of patients with PH and in experimental PH models, with predominant localization in endothelial cells (ECs) of remodeled distal pulmonary arteries. Endothelial TXNDC5 overexpression exacerbated pulmonary vascular remodeling, elevated right ventricular systolic pressure, and promoted right ventricular hypertrophy, whereas global or endothelial-specific TXNDC5 deficiency conferred protection against SuHx-induced PH. Hypoxia-induced factor (HIF)-2 transcriptionally activated TXNDC5 to drive PH development. Single-cell RNA sequencing identified a distinct subpopulation characterized by TXNDC5high extracellular matrix (ECM)-producing ECs. Bulk RNA sequencing combined with protein-protein interaction analysis revealed that TXNDC5 regulated ECM homeostasis through biglycan (BGN). Pharmacological inhibition of TXNDC5 with E64FC26 and endothelial-targeted TXNDC5 gene therapy significantly attenuated PH severity in rats. CONCLUSIONSOur study reveals that TXNDC5 is a main modulator to regulate ECM homeostasis and may serve as a promising target for the treatment of PH.

molecular biology↗

bioRxiv2025

Saxiphilin functions as a "toxin sponge" protein that counteracts the effects of saxitoxin poisoning

Saxitoxin (STX) is among the most potent toxins known, is classified as a chemical weapon, and is the archetype of the paralytic shellfish toxin (PST) family produced by marine and freshwater harmful algal blooms (HAB)1-3. STX causes paralysis and death through inhibition of voltage-gated sodium channels (NaVs), has no antidote, and poses a public health and commercial fishing threat due to its accumulation in seafood and increasing HAB occurrences1,4. Although STX is lethal to varied vertebrates5-7, including humans4,8,9, certain frogs resist STX poisoning6,7. This phenotype is thought to depend on soluble toxin sponge high-affinity STX binding proteins (saxiphilins, Sxphs)6,7,10,11 that provide resistance through a competition mechanism different from classic target site ion channel mutation mechanisms12-14. Here, we test this idea directly and show that a single dose of American bullfrog (Rana catesbeiana) Sxph (RcSxph) is sufficient to counteract STX neurotoxicity and lethality in mice using paradigms where STX and Sxph are administered together or sequentially in either order. Importantly, this function requires the RcSxph high-affinity STX binding site. Our findings provide in vivo validation that Sxphs are toxin sponges that protect against STX poisoning and highlight the potential to harness this protein class as antidotes for PSTs and other toxins.

pharmacology and toxicology↗

bioRxiv2025

Cold Atmospheric Plasma for Alzheimer's disease

Lightning has been proposed as a pivotal energy source driving prebiotic chemical evolution and early life processes. Similarly, external physical stimuli such as sound and light have been shown to modulate neurophysiological activity and mitigate Alzheimers disease (AD) pathology by promoting amyloid-{beta} (A{beta}) clearance. Here, we demonstrate that cold atmospheric plasma (CAP) acts as a joule-level analog of lightning, integrating light, sound, and reactive species to modulate AD progression in a mouse model. Using multimodal analyses, we show that CAP treatment enhances key neuroimmune signaling pathways in an AD murine model, including microglial activation, without inducing pathological alterations at the functional, transcriptomic, or proteomic levels in healthy mice. These findings highlight CAP as a safe and efficacious modality for modulating neurodegenerative processes, establishing a foundation for its therapeutic translation in AD and related disorders.

bioengineering↗

bioRxiv2025

Disruption of ADAMTSL4 Causes Ectopia Pupillae in Zebrafish via COL8A1-Driven Cell Migration

Congenital ectopia lentis (EL) poses a significant threat to visual outcomes in children. Although emerging causative genes have been identified, their biological functions remain poorly understood. In this study, we investigated the contribution of ADAMTSL4 variants to congenital EL in a cohort of 702 pedigrees. Pathogenic variants in ADAMTSL4 were identified in 23 probands (3.28%), comprising 29 distinct variants, with 14 being novel, making ADAMTSL4 the second most frequently mutated gene in the cohort. All affected individuals exhibited EL, and 26.09% also presented with ectopia pupillae (EP), also referred to as ectopia lentis et pupillae. To explore the functional consequences of ADAMTSL4 deficiency, we generated a CRISPR/Cas9-mediated adamtsl4-knockout zebrafish model, that faithfully recapitulated cardinal human disease features with an incidence comparable to that observed in affected patients. Histological and ultrastructural analysis revealed disrupted zonular fiber anchorage at the lens capsule, even in mutated eyes without overt EL or EP. Transgenic overexpression of adamtsl4 successfully reversed the ocular phenotypes, confirming the genes essential role in ocular development. Single-cell RNA-sequencing and fluorescence in situ hybridization demonstrated enriched ADAMTSL4/adamtsl4 expression in the equatorial lens epithelium, retinal pigment epithelium (RPE), iris anterior pigmented epithelium, and choroid fibroblast. Functional assays using zebrafish and human RPEs revealed that ADAMTSL4 deficiency compromised cell adhesion and promoted cell migration. Transcriptomic profiling revealed significant enrichment of extracellular matrix organization and cell adhesion pathways, with cross-species validation identifying consistent upregulation of COL8A1/col8a1b. Notably, COL8A1 knockdown in ADAMTSL4-deficient RPEs partially reversed the aberrant migratory phenotype, suggesting a functional interaction. Together, these findings establish ADAMTSL4 as a major causative gene in ectopia lentis et pupillae, highlight its role in orchestrating ocular integrity via regulation of extracellular matrix and cell behavior.

genetics↗

bioRxiv2025

Dual-Channel Event Microscopy for Ultrafast Biological Imaging

Many fundamental biological processes--spanning immune-tumor interactions, neuronal signaling, and microvascular flow--exhibit fast, multiscale dynamics among diverse cell types within three-dimensional tissue environments. Capturing such activity requires imaging systems that simultaneously achieve high temporal resolution, multicolor capability, and volumetric coverage over large fields of view (FOVs). However, existing modalities remain limited by trade-offs among imaging speed, spectral capacity, depth of field (DOF), and spatial resolution. Here, we present Dual-Channel Event Microscopy (DEM), which integrates digital micromirror device (DMD)-based pulsed illumination, extended-DOF optics, and event-based sensing for ultrafast, dual-channel volumetric imaging across a 2.3 x 1.3 mm2 FOV with an effective 200 {micro}m DOF. Using dual-color fluorescent phantoms and microsphere flow assays, DEM achieves accurate spectral separation and reconstruction of rapid motion at kilohertz frame rates. In vivo, DEM enables simultaneous visualization of neutrophils and premalignant tumors in freely swimming zebrafish. In immobilized specimens, it provides robust, sensor-level optical sectioning near the heart, suppressing diffuse background to reveal fine vascular networks and active blood circulation into and out of the cardiac chambers. DEM further enables quantitative mapping of blood-flow dynamics in the zebrafish tail, resolving arterial-venous differences and capturing heartbeat-driven oscillations that reflect cardiac pumping with high temporal fidelity. By uniting ultrafast acquisition, dual-channel capability, volumetric coverage, and intrinsic optical sectioning within a single event-driven architecture, DEM offers a powerful platform for visualizing rapid multicellular interactions and physiological dynamics in living systems.

bioengineering↗

bioRxiv2025

Histology-informed spatial domain identification through multi-view graph convolutional networks

Identifying spatial domains is crucial in spatial transcriptomics, yet effectively integrating gene expression, spatial location, and histology remains challenging. We present STESH, a Spatial Transcriptomics clustering method that combines Expression, Spatial information and Histology. STESH extracts histological features using a convolutional neural network and generates expression, histology, spatial, and collaborative convolution modules for a multi-view graph convolutional network with a decoder and attention mechanism. We evaluated STESH on multiple tissue types and technology platforms. STESH consistently outperformed ten state-of-the-art methods, achieving superior clustering accuracy with the highest scores in adjusted Rand index, normalized mutual information, and Fowlkes-Mallows index.

bioinformatics↗

bioRxiv2025

Blocking Nonspecific Primer Amplification in Loop-Mediated Isothermal Amplification with TrueLAMP

Loop-mediated isothermal amplification (LAMP) enables rapid nucleic acid detection but is vulnerable to primer-driven nonspecific amplification that can produce false-positive results. We developed TrueLAMP, a colorimetric LAMP formulation containing an inhibitor that suppresses nonspecific amplification while preserving target-dependent amplification. All 65 no-template controls across these studies remained negative, corresponding to 100% observed specificity. Using SARS-CoV-2 as a model and the Lamb primer set as a representative benchmark, TrueLAMP achieved a limit of detection of 250 copies per reaction with 95% detection probability. Endpoint color remained stable during extended incubation, reducing the need for time-critical readout. TrueLAMP was compatible with readily available heating devices, including a convection oven, water bath, and temperature-controlled smart mug. Independent evaluations in two external laboratories using additional primer-template systems, including DNA targets, further supported suppression of nonspecific amplification and sequence-dependent target detection. Together, these findings support TrueLAMP as a practical approach for improving the reliability of LAMP detection while retaining a simple isothermal workflow.

molecular biology↗

bioRxiv2025

Composite Likelihood Adjustment in Bayesian Inference for Estimating Species Tree Parameters Under the Multispecies Coalescent

Composite likelihood methods have long been used in biology to facilitate efficient computation for the high-dimensional, dependent structures commonly present in genetic data. In species-level phylogenetic inference under the multispecies coalescent model, the full likelihood is computationally intractable, while the composite likelihood can be efficiently computed. However, using the composite likelihood instead of the full likelihood in Bayesian inference involves repeated use of data, resulting in overly concentrated posteriors. We develop a method that incorporates an adjustment to the composite likelihood in a Bayesian framework to adjust the approximated posterior distributions so that credible intervals achieve the correct coverage. Both simulated and empirical data are used to show that our method compares favorably with existing methods with respect to both computation time and accuracy.

evolutionary biology↗