Biology subjects

Qu, C.

Publications and source records attributed to Qu, C..

At least 19 recordsLinked to original sources

bioRxiv2026

Daytime Napping and Associative-Memory Retrieval Speed: An Exploratory Behavioral and EEG Study

Purpose: To test whether a daytime nap was associated with improved associative-recognition performance relative to monitored wakefulness and to determine where any response-time (RT) difference occurred in the RT distribution. Methods: Fifteen healthy students completed nap and wake sessions in a within-participant design. Each session included word-pair learning, immediate recognition, a 60-min interval, and delayed recognition without additional study. Trial-level log RT was the focal outcome; accuracy and electroencephalography (EEG) were complementary outcomes. Results: The RT Condition-by-Time interaction was significant (b = -0.063, 95% CI [-0.117, -0.009], p = .027). Responses were 6.7% faster after the nap (p = .010) but did not change after wakefulness (p = .704), with the difference concentrated among slower responses. Accuracy showed no condition-specific change (p = .401). Nap EEG showed aperiodic spectral slowing and stronger periodic sigma activity, but no EEG measure explained the RT effect. Conclusions: Daytime napping was associated with faster delayed associative recognition, primarily through attenuation of the slowest responses. The exploratory findings warrant larger confirmatory studies.

neuroscience↗

bioRxiv2026

Assessing fish biodiversity and community structure in the Ganjiang River using eDNA metabarcoding

Hydropower development has emerged as a major driver of global environmental change, causing significant ecological damage to freshwater ecosystems and threatening aquatic biodiversity. However, the impact of cascade dams on fish communities in large river systems remains poorly understood, particularly in biodiversity hotspots such as China. Here, we used environmental DNA (eDNA) metabarcoding to assess the spatiotemporal patterns of fish diversity and community structure in the Ganjiang River, the largest tributary of the Yangtze River, in relation to cascade hydropower development. We collected water samples from 19 sites along the main stem and major tributaries in both wet and dry seasons, and analyzed the eDNA data using high-throughput sequencing and advanced bioinformatics pipelines. Our results revealed significant seasonal and spatial variations in fish diversity and community composition, with lower species richness and distinct assemblages in the impounded sections upstream of the dams compared to the downstream reaches. The fish communities were strongly influenced by environmental factors such as water temperature, pH, dissolved oxygen, and nutrients, which exhibited complex interactions with dam operation and land use practices. Spatial scale analyses further indicated that the impact of dams on fish diversity was most pronounced at the local scale, but also detectable at the regional scale. Our findings provide novel insights into the ecological consequences of cascade hydro-power development on fish communities and highlight the importance of considering spatial scales and environmental heterogeneity in assessing the impacts of human activities on freshwater biodiversity. Our study demonstrates the power of eDNA metabarcoding as a cost-effective and non-invasive tool for biodiversity assessment and conservation planning in large river systems facing multiple stressors and knowledge gaps.

ecology↗

bioRxiv2026

Single-molecule imaging of DNA repair and cytoplasmic rigidification in intracellular bacteria

DNA damage is an important component of the antibacterial response of phagocytes, but which DNA repair mechanisms are active in intracellular bacteria remains unclear. We developed a live-cell single-molecule tracking approach to directly measure DNA repair activity in Escherichia coli within macrophages. Phagocytosis activates bacterial base excision and nucleotide excision repair pathways and increases DNA mismatch repair foci indicative of DNA replication errors. Phagocyte-generated stresses also cause a general slowdown in protein diffusion within bacteria, consistent with a transition of the cytoplasm towards a glass-like state, which is associated with reduced metabolic activity. At the single-cell level, DNA repair activity is highly heterogeneous, with metabolically inactive bacteria showing the greatest engagement of repair proteins. Together, these findings reveal how distinct DNA repair pathways are deployed during macrophage infection and link repair activity to the metabolic and biophysical states of individual intracellular bacteria.

microbiology↗

bioRxiv2026

Impact of cathelicidin cleavage by SpeB on Streptococcus pyogenes CovRS signaling

Cathelicidins are a class of antimicrobial peptides (AMPs) that are part of the first line of defense of the innate immune system. While cathelicidin-derived peptides such as LL-37 can be directly bactericidal, Streptococcus pyogenes (Spy; Group A Streptococcus) is highly resistant to killing. Furthermore, Spy detects LL-37 through the CovRS two-component system to regulate its virulence factors. One effect of this signaling is the repression of expression of the bacterial protease SpeB. Prior work has also shown that SpeB, along with other bacterial proteases can cleave LL-37. However, it is unclear if SpeB cleavage of LL-37 impacts antimicrobial function and CovRS signaling activity. Using a genetic approach, we show that the presence SpeB did not significantly impact the killing of Spy by LL-37 relative to other known resistance factors. Furthermore, while SpeB cleaves LL-37, CovRS maintains sensitivity to LL-37 fragments. These results indicate that SpeB cleavage of LL-37 does not negatively impact virulence factor regulation in Spy.

microbiology↗

bioRxiv2026

A shear lag model of the podocyte foot process network predicts a mechanical feedback loop driving progressive effacement

The podocyte foot process network forms the final barrier of the kidneys glomerular filtration system. Under mechanical stress this network is prone to injury in which podocytes lose connectivity to their neighbors and begin the progression toward effacement, but what governs its mechanical resilience is unknown. We show that the network is built like a lap joint: two major processes coupled through interdigitating foot processes, a configuration that behaves as a classical shear lag system, with force concentrating at the joint ends and decaying over a characteristic transfer length set by geometry and stiffness. A discrete network model reproduces the continuum shear lag solution and identifies a hierarchy among governing parameters, with cytoskeletal stiffening of the major process amplifying foot process force more potently than basement membrane stiffness. Applying the model to morphometric data from puromycin aminonucleoside nephrosis, a model of human minimal change disease and early focal segmental glomerulosclerosis, reveals a mechanical positive feedback loop: force concentration drives foot process loss, which raises force on surviving segments and accelerates further loss. This nonlinear amplification implies a threshold beyond which failure becomes self-sustaining, analogous to the critical crack length in fracture mechanics.

biophysics↗

bioRxiv2026

Conformational Basis of Functionally Selective Allosteric Modulation of the Angiotensin II type 1 Receptor by Small Molecules

Blockade of signaling through the angiotensin II type 1 receptor (AT1R), a prototypical G protein-coupled receptor (GPCR), by angiotensin receptor blockers (ARBs) is a major therapeutic approach to treating a wide variety of cardiovascular and renal diseases1. Like most GPCRs, the AT1R signals through two transducers, G proteins and {beta}-arrestins2,3. Previous reports have described {beta}-arrestin-biased peptide orthosteric agonists for the AT1R with potential therapeutic advantages over currently available unbiased ARBs4-6. Here we report the DNA- encoded library screening-guided isolation and pharmacological characterization of the first small molecule AT1R allosteric ligands. We use cryo-electron microscopy, double electron- electron resonance spectroscopy, molecular dynamics simulations, and targeted mutagenesis to determine their binding sites, binding modes and conformational mechanisms driving their unique and divergent modulatory effects on G protein and {beta}-arrestin pathways. Our findings uncover new mechanisms for precisely controlling the dynamic behavior of the AT1R with implications for drug development targeting this pathophysiologically important receptor family.

biochemistry↗

bioRxiv2026

The Attentional Thief: How Self-Paced Visual Exploration Compresses Subjective Time

Social media users often feel that time vanishes while scrolling, but real feeds confound novelty, rewards, social signals, and self-paced control, leaving the driver of this distortion unclear. We tested whether self-paced visual exploration is sufficient to compress subjective time by comparing active scrolling with passive, yoked viewing and a static baseline. Twenty-three adults viewed sequences of natural images under three within-subject conditions: Scrolling (self-paced mouse clicks), Watching (a passive, yoked replay of their own scrolling sequence), and a Baseline (a static image). Participants estimated the elapsed duration of each block. Subjective duration was most compressed under Scrolling (48% of elapsed time), followed by Watching (51%) and Baseline (65%). Two sources separated these effects. Adding back the empty inter-image fixations brought the image-rich conditions to within seconds of the Baseline, showing that observers barely counted the blank gaps; the Scrolling-Watching difference, by contrast, was independent of these shared gaps, isolating self-paced control as a second source of compression. Electrophysiology linked that control to anticipatory neural states and the timing of early visual responses, with no amplified encoding of individual images. The results favor an attention-weighted account of timing, on which subjective duration tracks how much attention reaches the clock, a resource that a self-paced stream and its uncounted gaps both draw away.

neuroscience↗

bioRxiv2026

Precision-Weighted Updating Explains Serial Dependence Across Sensory and Contextual Transitions

Serial dependence is influenced by sensory uncertainty and contextual continuity, but it remains controversial whether these influences reflect separate mechanisms or different expressions of a shared updating process. Across two time reproduction experiments (N = 44), we examined how motion coherence and coherence transitions modulated the attraction of recent temporal history while controlling for central tendency effects from the current stimulus. In Experiment 1, the low coherence led to stronger serial dependence compared to the high coherence. In Experiment 2, enhanced coherence categories introduced salient contextual boundaries; serial dependence was markedly stronger on the same category transition than switch transition. A three-state Kalman filter model, comprising fast (serial dependence), slow (central tendency), and bias (decision carryover) states captured these patterns through coherence-dependent modulation of fast-state process noise and Kalman gain. Within the tested model space, this precision-weighting account was selected in both experiments; with little evidence that an explicit state reset was needed. These findings support the precision-weighted updating account in which recent history is weighted according to the reliability and stability of the current perceptual environment.

neuroscience↗

bioRxiv2026

Neural Substrates of Duration Serial Dependence: Opposing Modulation in Basal Ganglia and Posterior Medial Cortex

Perceptual judgments are systematically biased toward recent experience, a phenomenon called serial dependence. The brain circuits underlying this effect in time perception remain unknown. Using fMRI, we identified the neural substrates of duration serial dependence and tested whether they overlap with those for motion direction. Twenty-seven participants reproduced either the duration or direction of a visual stimulus; a retro-cue revealed which feature to report 3-s after stimulus onset, separating memory-trace signals from task-switching signals. Duration serial dependence was robust and roughly four times stronger on task-repeat than task-switch trials; direction serial dependence was near zero. The previous duration produced opposing responses in the bilateral putamen (suppression) and in the posterior cingulate cortex and precuneus (reinstatement); no analogous signal emerged for direction. Task switching from direction to time task engaged the inferior frontal junction and the dorsolateral prefrontal cortex, which carried no serial dependence signal. The anatomical dissociation resolves the behavioral pattern: the duration trace is encoded in the putamen and posterior medial cortex on every trial, but task-set reconfiguration by the frontoparietal network gates its read-out into behavior, explaining the task repetition effect. These results reveal a dissociation between two functionally distinct circuits: the putamen and posterior cingulate/precuneus carry signals from the previous trial, whereas frontoparietal regions support task switching but carry little serial dependence information.

neuroscience↗

bioRxiv2026

Central amygdala Isl1 neurons control biting by integrating sensory and motivational signals

Efficient orofacial motor control is essential for adaptive interactions with the environment, yet the neural substrates that regulate the force and precision of biting remain poorly understood. Here, we identify a subpopulation of neurons in the central amygdala (CeA) expressing the transcription factor Isl1 (CeAIsl1) that plays a crucial role in modulating biting behavior in mice. In vivo calcium imaging revealed that CeAIsl1 neurons are robustly activated at the onset of biting across materials of varying physical properties, with distinct neuronal ensembles selectively encoding responses to the physical properties of the objects. CeAIsl1 neuronal activity scales positively with the hardness of the object, suggesting a role in force modulation. Optogenetic activation of CeAIsl1 neurons enhances biting behavior toward edible or non-edible objects, induces fictive feeding in the absence of physical targets and exerts a reinforcing effect on behavior, whereas inhibition of CeAIsl1 neurons impaired efficient biting of solid food by reducing jaw-closing muscle activity. Projection-specific manipulations revealed that activation of CeAIsl1 projections to the parvocellular reticular formation (PCRt) and pedunculopontine tegmental nucleus (PPtg) increased the duration and frequency of biting, with CeAIsl1-to-PPTg stimulation producing a positive motivational valence. These findings uncover a previously unrecognized sensorimotor function of the central amygdala in calibrating bite force and precision, linking motivational states to skilled motor output.

neuroscience↗

bioRxiv2026

Synaptopodin enables directional mechanoadaptation of integrin-based adhesions

The attachment of cells to their substrate through adhesion complexes is fundamental to tissue architecture and function. These adhesions are inherently optimized to resist shear forces parallel to the substrate, yet certain specialized cells must also withstand substantial perpendicular forces. How cells adapt their adhesion machinery to resist forces in different directions has remained unclear. In the kidney, podocytes experience perpendicular forces from pressurized filtrate flow while maintaining attachment to the glomerular basement membrane through integrin-based adhesions. Here we show that synaptopodin converts adhesions from shear-resistant to perpendicular force-resistant structures through coordinated reorganization of the actin cytoskeleton and adhesion complexes. Using an inertial force application system, we demonstrate that synaptopodin triggers force-dependent redistribution of {beta}1-integrin to the cell periphery specifically in response to perpendicular loading, while synaptopodin-deficient cells lack this directional adaptation and detach. This mechanism operates in multiple cell types and is physiologically essential: synaptopodin-null mice subjected to elevated glomerular pressure develop significant proteinuria and podocyte foot process effacement. These findings reveal a molecular basis for directional mechanoadaptation, whereby a single protein enables cells to reconfigure their adhesion architecture in response to the direction of applied force.

biophysics↗

bioRxiv2026

Orthogonal Force Balance Between Contractility and Shear Stress Governs Podocyte Dynamics

Maintenance of tissue barriers under mechanical stress represents a fundamental biological challenge across organ systems. In the kidney, podocyte cells withstand highly variable hemodynamic forces while preserving a tensioned, nanostructured filtration barrier. Dysregulation of this barrier leads to significant pathology, but the mechanical principles underlying homeostasis of cells against flow of filtrates have not yet been identified. Here, we uncover a counterintuitive mechanical homeostasis mechanism whereby podocyte attachment depends on a dynamic balance between external fluid shear stress and internal cellular contractility. Integrated biomechanical modeling and experiment reveal a previously unrecognized mechanosensing circuit that optimizes integrin distribution at foot process peripheries. Our mathematical framework for cell-matrix adhesion stability reveals, surprisingly, that reducing blood pressure can worsen outcomes when cell contractility is impaired, contrary to clinical belief that lowering blood pressure universally benefits cellular adhesion and kidney function. We validated this principle through mouse models with manipulated blood pressure and myosin inhibition, demonstrating that concurrent reduction of both shear stress and contractility worsens podocyte injury and proteinuria. Super-resolution microscopy confirms our predicted integrin redistribution patterns under these mechanical perturbations. These findings establish a fundamental mechanobiological principle applicable beyond nephrology, and suggest potential treatment pathways targeting non-equilibrium steady states.

cell biology↗

bioRxiv2025

Neddylation Regulates Mitochondrial Dynamics and Turnover in the Adult Heart

BACKGROUNDDisruption of mitochondrial homeostasis drives cardiomyopathy and heart failure, yet upstream regulatory mechanisms remain poorly defined. Neddylation, a reversible post-translational conjugation of the ubiquitin-like protein NEDD8 by E1/E2/E3 enzymes, is essential for cardiac morphogenesis, but its role in the adult heart is unknown. METHODSWe assessed the relevance of neddylation to human cardiac disease by gene set enrichment analysis of ischemic (ICM) and non-ischemic cardiomyopathy (NICM) datasets and by immunoblotting and qPCR of ventricular tissue from patients with ICM or dilated cardiomyopathy (DCM). In adult mice, we induced cardiomyocyte-restricted deletion of the NEDD8-activating enzyme 1 (NAE1) by tamoxifen injection and monitored cardiac function at baseline and after transverse aortic constriction (TAC). Bulk RNA-seq 4 weeks post-tamoxifen was combined with bioenergetic, biochemical, and ultrastructural analyses. To assess mitochondrial dynamics, we generated NAE1/MFN2 and NAE1/DRP1 double-knockout mice. Cullin activity, mitochondrial ubiquitination, and mitophagy were measured in hearts and cultured cardiomyocytes. RESULTSNeddylation pathways were dysregulated in human ICM and NICM datasets and in failing ICM/DCM myocardium. Cardiomyocyte-specific NAE1 deletion caused systolic dysfunction and heart failure by 10 weeks post-tamoxifen, culminating in premature death and exacerbating TAC-induced pressure-overload heart failure. At 4 weeks, NAE1 loss repressed metabolic and mitochondrial bioenergetic programs, reduced ATP production, and impaired respiration. Electron microscopy revealed elongated mitochondria and accumulated mitophagic vesicles, with dysregulation of DRP1, MFN2, PINK1, LC3-II, and p62. DRP1/NAE1 co-deletion accelerated systolic failure relative to either single knockout, whereas MFN2/NAE1 co-deletion did not alter early disease progression, implicating pathogenic mitochondrial hyperfusion. Genetic NAE1 depletion in vivo and pharmacologic NAE1 inhibition in vitro impaired mitophagic vesicle formation and flux, inactivated cullin scaffold proteins, reduced mitochondrial ubiquitination, and blunted mitophagic clearance. CONCLUSIONSCardiac neddylation preserves adult heart function by coordinating mitochondrial fusion-fission dynamics and sustaining cullin-dependent ubiquitination and turnover of damaged mitochondria. These findings identify neddylation as a key regulator of mitochondrial quality control and link its disruption to human cardiomyopathy. Therapeutically, targeting the neddylation-cullin axis may limit mitochondrial dysfunction, enhance mitophagy, and improve energetic reserve in failing hearts, while neddylation signatures in patient myocardium may help guide stratification and precision therapy for cardiomyopathy. Clinical PerspectiveO_ST_ABSWhat Is New?C_ST_ABS* Demonstrates for the first time that the NEDD8-activating enzyme (NAE1)driven neddylation pathway is indispensable for maintaining mitochondrial quality control in the adult heart. * Links loss of neddylation to mitochondrial hyperfusion, impaired mitophagy, and rapid progression to heart failure. * Reveals that neddylation promotes cullin-RING ligase-mediated ubiquitination of damaged mitochondria, coupling mitochondrial dynamics with turnover. What Are the Clinical Implications?* Restoring or enhancing cardiac neddylation may represent a novel therapeutic avenue for cardiomyopathies characterized by mitochondrial dysfunction. * Pharmacologic agents that bolster DRP1-dependent fission or activate cullin neddylation could potentially normalize mitochondrial dynamics and improve myocardial energetics. * Conversely, systemic neddylation inhibitors now in oncology trials warrant careful cardiac monitoring, as they may precipitate mitochondrial injury and heart failure. * Circulating or tissue markers of neddylation might help stratify patients at heightened risk for mitochondrial-driven cardiac disease and guide precision therapy.

physiology↗

bioRxiv2025

Computer Vision Methods for Spatial Transcriptomics: A Survey

Spatial transcriptomics (ST) enables the simultaneous measurement of gene expression and spatial localization within tissue sections, providing unprecedented opportunities to dissect tissue architecture and functional organization. As a relatively new omics technology, bioinformatics has driven much of the innovation in ST. However, within these frameworks, "spatial" information is often reduced to locations and relationships between molecular profiles, without fully leveraging the wealth of submicron morphological detail and histological knowledge available. Advances in computer vision-based artificial intelligence (AI) are opening exciting new avenues beyond conventional bioinformatics approaches by modeling complex histological patterns and linking morphology to molecular states. More excitingly, they bring fresh perspectives to potentially address key limitations of ST, including its high cost, limited clinical applicability, and reliance on twodimensional (2D) analysis of inherently three-dimensional (3D) tissues. For instance, models that predict ST directly from histology images enable "virtual sequencing," drastically reducing costs while integrating morphological insights from pathology with molecular biomarkers, thus accelerating clinical translation. Moreover, computer vision techniques can reconstruct pixel-aligned 3D tissue models, overcoming the technical barriers of 2D acquisition and advancing 3D spatial omics analytics. In this paper, we present the first systematic survey of computer vision AI models for ST analytics, categorizing approaches across architectures, learning paradigms, tasks, and datasets, and tracing their technological evolution. We highlight key challenges and future directions, offering a panoramic perspective on vision-driven ST and its potential to transform both basic research and clinical practice. The curated collection of vision-driven spatial transcriptomics papers is available at https://github.com/hrlblab/computer_vision_spatial_omics.

bioinformatics↗

bioRxiv2025

Developing a versatile technology for agroinfiltration in multiple plants

Agrobacterium-mediated transient transformation methods are widely used in plant science and molecular pharming. However, plant immune response and post-transcriptional gene silencing (PTGS) can compromise gene expression, limiting the adaptability of these methods across plant species. The lack of a robust reporter system further hinders advancements in agroinfiltration technology. To address these challenges, we developed a fungal bioluminescence pathway (FBP)-based reporter system that utilizes caffeic acid to generate self-sustained luminescence. By incorporating NahG and P19, our FBP assay enhances transient transformation efficiency in over 20 plant families, including major crops, vegetables, ornamental plants, and trees. Furthermore, we demonstrate its utility for assessing protein localization, interactions, and transcriptional regulation in multiple plant species, thereby broadening our understanding of gene function throughout the plant kingdom.

plant biology↗

bioRxiv2024

Multi-omics analysis reveals the mechanism of BnC07MYB3a is involved in seed coat color in Brassica napus L.

In rapeseed (Brassica napus), yellow-seeded varieties accumulate less flavonoid pigments (anthocyanins/proanthocyanidins) in their seed coats compared with black-seeded varieties. The yellow-seeded trait is associated with greatly improved seed oil yield, quality, and commercial value. Many R2R3 MYB activators have been characterized in rapeseed, but how MYB-type repressors affect pigment biosynthesis is not yet fully understood. In this study, we performed transcriptome sequencing and metabolomic analysis of B. napus varieties with extreme differences in seed coat color, combined with weighted gene co-expression network analysis. This analysis identified an R2R3-MYB-type transcription factor, BnC07MYB3a (BnaC07G0178800ZS), as a candidate regulator of the yellow-seeded trait in B. napus. Overexpressing BnC07MYB3a in Arabidopsis thaliana and B. napus downregulated the expression of flavonoid biosynthetic genes, resulting in significantly lower anthocyanin and proanthocyanidin accumulation than in the wild-type and a lighter seed coat color in transgenic plants. BnC07MYB3a directly binds to the promoter of the TRANSPARENT TESTA (TT) gene BnTT6 and represses its expression. BnC07MYB3a also physically interacts with BnA06bHLH92a and the WD40 transcription factor TRANSPARENT TESTA GLABRA1 (BnTTG1), suggesting that they might form a previously unidentified MYB-bHLH-WD40 transcription factor complex. Our results reveal the molecular mechanism and regulatory network of BnC07MYB3a in determining seed coat color in B. napus and provide a genetic resource for breeding yellow-seeded cultivars of B. napus.

molecular biology↗

bioRxiv2024

Abnormal activation of the mineralocorticoid receptor in the aldosterone-sensitive distal nephron contributes to fructose-induced salt-sensitive hypertension

Fructose high-salt (FHS) diets increase blood pressure (BP) in an angiotensin II (Ang II)-dependent manner. Ang II stimulates aldosterone release, which, by acting on the mineralocorticoid receptor (MR), regulates Na+ reabsorption by the aldosterone-sensitive distal nephron (ASDN). The MR can be transactivated by glucocorticoids, including those locally produced by 11{beta}-HSD1. The epithelial sodium channel (ENaC) is a key transporter regulated by MRs. We hypothesized that fructose-induced salt-sensitive hypertension depends in part on abnormal activation of MRs in the ASDN with consequent increases in ENaC expression. We found that aldosterone-upregulated genes in mice ASDN, significantly overlapped with 74 genes upregulated by FHS in the rat kidney cortex (13/74; p[≤]1x10-8), and that these 74 genes are prominently expressed in rat ASDN cells. Additionally, the average z-score expression of mice-aldosterone-upregulated genes is highly correlated with FHS compared to glucose high-salt (GHS) in the rat kidney cortex (Pearson correlation; r=0.66; p[≤]0.005). There were no significant differences in plasma aldosterone concentrations between the FHS and GHS. However, 11{beta}-HSD1 transcripts were upregulated by FHS (log2FC=0.26, p[≤]0.02). FHS increased BP by 23{+/-}6 mmHg compared to GHS, and blocking MRs with eplerenone prevented this increase. Additionally, inhibiting ENaC with amiloride significantly reduced BP in FHS from 148{+/-}6 to 134{+/-}5 mmHg (p[≤]0.019). Compared to GHS, FHS increased total and cleaved ENaC protein by 89{+/-}14 % (p[≤]0.03) and 47{+/-}16 % (p[≤]0.01) respectively. FHS did not change {beta}- or {gamma}-subunit expression. These results suggest that fructose-induced salt-sensitive hypertension depends, in part, on abnormal Na+ retention by ENaC, resulting from the activation of MRs by glucocorticoids.

physiology↗

bioRxiv2024

StereoMM: A Graph Fusion Model for Integrating Spatial Transcriptomic Data and Pathological Images

Spatially resolved omics technologies generating multimodal and high-throughput data lead to the urgent need for advanced analysis to allow the biological discoveries by comprehensively utilizing information from multi-omics data. The H&E image and spatial transcriptomic data indicate abundant features which are different and complementary to each other. AI algorithms can perform nonlinear analysis on these aligned or unaligned complex datasets to decode tumoral heterogeneity for detecting functional domain. However,the interpretability of AI-generated outcomes for human experts is a problem hindering application of multi-modal analysis in clinic. We presented a machine learning based toolchain called StereoMM, which is a graph fusion model that can integrate gene expression, histological images, and spatial location. StereoMM firstly performs information interaction on transcriptomic and imaging features through the attention module, guaranteeing explanations for its decision-making processes. The interactive features are input into the graph autoencoder together with the graph of spatial position, so that multimodal features are fused in a self-supervised manner. Here, StereoMM was subjected to mouse brain tissue, demonstrating its capability to discern fine tissue architecture, while highlighting its advantage in computational speed. Utilizing data from Stereo-seq of human lung adenosquamous carcinoma and 10X Visium of human breast cancer, we showed its superior performance in spatial domain recognition over competing software and its ability to reveal tumor heterogeneity. The fusion approach for imaging and gene expression data within StereoMM aids in the more accurate identification of domains, unveils critical molecular features, and elucidates the connections between different domains, thereby laying the groundwork for downstream analysis.

bioinformatics↗