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Biology subjects

Long, C.

Publications and source records attributed to Long, C..

At least 19 recordsLinked to original sources

LRRC37A is essential for acrosomal ion homeostasis and male fertility

Mammalian spermatozoa face various challenges during their long march to the destination. As a specialized membrane-bound organelle in the sperm head, the acrosome is particularly sensitive to changes in ionic and osmotic conditions, yet how acrosomal ion homeostasis is maintained remains largely unknown. Here, we show that LRRC37A is required for acrosomal ion homeostasis. Loss of Lrrc37a causes complete male infertility, accompanied by pronounced enlargement and deformation of the acrosome in the sperm head. Acrosome biogenesis was not affected by Lrrc37a knockout during the early stages of spermiogenesis, whereas acrosomal enlargement emerged at later stages and became more pronounced in the epididymis. LRRC37A localized to the outer acrosomal region and interacted with the Na/K-ATPase -subunit isoforms ATP1A1 and ATP1A4. Loss of LRRC37A disrupted the spatial distribution of both isoforms and was accompanied by increased Na within the acrosomal region. In addition, pharmacological perturbation of Na/K-ATPase activity or cellular ion homeostasis induced acrosomal swelling. These findings establish an essential role for LRRC37A in acrosomal ion homeostasis, suggesting that its deficiency may be associated with a distinct form of teratozoospermia characterized by acrosomal enlargement.

cell biology↗

The HES1-SOD1 Antagonism Shapes Senescence Heterogeneity and Impacts Metastatic Relapse of Circulating Tumor Cells

Circulating tumor cells (CTCs) encounter multiple challenges within the blood microenvironment, including oxidative stress, flow shear forces, and immune surveillance, often leading to anoikis. Recently, a transitional state of CTC senescence has been identified, contributing to metastatic inefficiency. However, the molecular mechanisms linking senescent CTCs to disease relapse remain to be defined. By integrating a genetic model of cortactin knockdown-induced CTC senescence with single-cell multi-omic analyses, we revealed two distinct senescent CTC subpopulations marked by HES1 expression levels. These HES1low and HES1high subpopulations exhibited differential evolutionary trajectory dynamics and unique molecular and metabolic signatures, which were significantly correlated with adverse clinical outcome across several patient cohorts. HES1low senescent CTCs displayed enhanced mitochondrial fitness, oxidative phosphorylation, and ROS-detoxifying capabilities, resulting in more efficient tumor regrowth with a pro-inflammatory and thrombotic phenotype when compared to the HES1high group. Mechanistically, HES1 directly bound to the Sod1 promoter and repressed its expression, leading to redox imbalance and mitochondrial dysfunction that were linked to weakened tumor regrowth capacity. Both senescent CTC subpopulations were broadly resistant to cytotoxic and targeted therapies, yet they showed elevated dependency on anti-apoptosis programs that make them susceptible to dual blockade by SOD1 inhibitor and the anti-senolytic drug ABT737 in vivo. Finally, in a prospective cohort of on-treatment melanoma patients, HES1 senescent CTCs were highly enriched in patients with progressive disease. Thus, the HES1-SOD1 antagonism shapes CTC senescence heterogeneity and contributes to differential tumor relapse, which can be therapeutically explored for eliminating residual metastatic disease.

cancer biology↗

Energetic constraints shape the diversity of feasible ecological networks

The relationship between energy supply and biodiversity is a longstanding question in ecology. Although a monotonic increase in diversity with energy availability is often assumed, unimodal species-energy relationships have been widely documented across ecosystems, and their origin from first principles remains unclear. Here, we develop a geometric framework that recasts ecological feasibility in explicitly energetic terms. By treating total energy supply as a system-level constraint on an energy-based network model, we define nested feasibility domains in the space of energy capture rates and quantify feasibility probabilities as their volume ratios. We show that the probability of initializing a feasible network increases monotonically and saturates with energy supply, whereas the probability of sustaining steady-state biomass follows a unimodal relationship--revealing a bounded energetic window within which network maturation is most likely. Extending this analysis to all candidate subcommunities via feasibility partitions, we find that different community sizes are most feasible at different energy levels, and that average diversity itself peaks at intermediate supply. Together, these results suggest that energetic constraints determine the diversity of ecological networks not through energy scarcity alone, but through the geometric interplay between external energy supply and internal energy exchange. Author SummaryWhy do many ecosystems show the highest biodiversity not where energy is most abundant, but at intermediate levels? This unimodal species-energy relationship has been documented across grasslands, wetlands, and rainforests, yet its origin from first principles has remained unclear. We approached this question by developing a simplified model that treats ecological networks as energy-processing systems. In this model, each species captures energy from the environment and exchanges it with others, and the total energy available to the network is explicitly limited. By measuring how the likelihood of species coexistence changes with energy supply within this framework, we found that while a minimum energy threshold is needed for any community to persist, too much energy can paradoxically reduce the chance of long-term coexistence. This creates a bounded energy window most favorable for community persistence. When we extended the analysis to all possible subsets of species, we found that different-sized communities are most likely to persist at different energy levels, and that overall expected diversity peaks at intermediate supply. These results suggest a possible geometric origin for why more energy does not always support more species, providing a theoretical baseline for connecting the structure of energy flow within networks to observed biodiversity patterns.

ecology↗

Long-read proteogenomic atlas of human neuronal differentiation reveals isoform diversity informing neurodevelopmental risk mechanisms

RNA splicing shapes neuronal identity and disease risk, yet current maps lack the developmental resolution and depth to resolve this complexity. Here, we integrate deep long-read RNA sequencing and proteomics in iPSC-derived cortical neurons to generate a high-resolution proteogenomic atlas of human neuron development. We identify 182,371 mRNA isoforms (over half previously unknown) and provide direct peptide evidence for the translation of hundreds of novel protein-coding sequences. Population genetics demonstrates that variants affecting novel exons and splice sites are under negative selection, underscoring the potential significance of these isoforms. During neuronal maturation, we observe that ASD risk genes undergo dynamic isoform switching, including microexon inclusion and intron retention, that remodel key protein domains and regulatory regions. Furthermore, we uncover widespread, long-range coordination between splicing and polyadenylation. Finally, our atlas enables variant reinterpretation in ASD, highlighting the value of an isoform-centric view for interpreting pathogenic variation in neurodevelopment.

bioinformatics↗

On the energetic boundaries of trophic systems

Energy is the fundamental currency of life. Every organism requires a minimum intake to meet maintenance needs, and every trophic transfer dissipates part of the energy flow as heat. Classical theory has emphasized lower bounds on supply--the minimum resource level required for consumers to persist--yet the possible upper bounds and their role in limiting food-chain length remain unclear. We develop a thermodynamically grounded framework that reveals a triad of boundaries: (i) consumer thresholds, (ii) a basal protection limit that reframes the paradox of enrichment as a thermodynamic constraint, and (iii) environmental or physiological supply caps. We show that the intersection of these three boundaries determines the exact range of conditions under which a given ecosystem structure can occur, and that within this range trophic configurations arise as the unique solution that maximizes energy flow. As chain length increases, consumer thresholds rise while the basal protection limit falls, causing this range to contract and eventually disappear. Whether this limit is reached depends on the relative position of these two boundaries and the external supply cap. Their crossing defines an energetic ceiling: a thermodynamic bound on food-chain length beyond which no further level can be sustained. Our results show that feasibility conditions are directly shaped by thermodynamic laws, providing a mechanistic explanation for the emergence and limits of trophic systems.

ecology↗

A matrix-mimicking bioadhesive epicardium for tunable modulation of biomechanics in the acutely infarcted heart

Mitigating adverse tissue remodeling after a heart attack or myocardial infarction (MI) is critical to prevent the development of heart failure. Among various post-MI treatment strategies, mechanical reinforcement of the infarcted region with epicardial patches has promise due to its consistent improvement of chronic cardiac function and its drug- or biologic-free nature. However, despite the variety of patch materials studied to date, the lack of a programmable platform that predictably modifies early-stage cardiac biomechanics to different degrees has prevented further optimization of this strategy. Here, we introduce the matrix-mimicking bioadhesive epicardium (MMBE), a platform that can be rationally designed to achieve a wide range of anisotropic mechanical properties to offer quantifiable mechanical reinforcement of the heart upon application. The platform synergistically combines fully programmable direct-ink-writing of extracellular matrix-inspired crimped fibers and a bioadhesive for sutureless integration to the epicardium. The MMBE platform achieves an array of matrix-mimicking mechanical properties and acute modulation of cardiac biomechanics using numerical analysis, in silico studies and experimental characterizations. Furthermore, the feasibility of the MMBE platform in an in vivo rat model of MI is demonstrated. The MMBE platform can be used to systematically identify patch design parameters that alter post-MI remodeling without introducing confounding biological variables.

bioengineering↗

Linking power, efficiency, and bifurcations in ecological systems

Three hypotheses help organize energetic thinking about living systems: Lotkas Maximum Power Principle, Odum-Pinkertons Intermediate Efficiency Principle, and Morowitzs Biological Cycling Principle. Here we show how these hypotheses fit together in consumer-resource systems, moving from qualitative principles to formal, testable statements. Using the Rosen-zweig-MacArthur model, we prove that the consumers maximum output power lies exactly on the Hopf boundary that separates stable points from cycles; at that point, the resulting power efficiency is intermediate. In the Rosenzweig-MacArthur model the Hopf is supercritical, so a stable limit cycle appears smoothly as the equilibrium loses stability. We treat the Hopf onset of time-periodic population oscillations as a population-level analogue of sustained cycling under energy flux. We then embed these energetic statements in adaptive dynamics: with convex trait costs, evolutionary singular strategies exist and are locally stable, but they coincide with the maximum-power state only under explicit marginal-cost conditions. Together, these results unify classic ideas in the concrete setting of consumer-resource systems and suggest measurements to evaluate when bifurcations, energetics, and evolution can converge.

ecology↗

Malignant ascites enhance γδ T cell cytotoxicity towards ovarian cancer via modulating chemokines secretion from the cancer cells that recruits γδ T cells

Ovarian cancer patients usually develops peritoneal metastasis and malignant ascites in the advanced stages, which form immuno-suppressive tumor microenvironments that limit the efficacy of immuno-therapies. However, during our previous research trying to develop a {gamma}{delta} T cell-based cell therapy, we noticed that the malignant ascites may enhance the cytotoxicity of {gamma}{delta} T cells towards ovarian cancer cells. Herein, in this work we showed that the phenomenon is real and the low molecular weight components in the ascites act on the cancer to promote the killing by {gamma}{delta} T cells. Transcriptome analysis and in vitro experiments revealed that the malignant ascites induce the secretion of chemokines CXCL2 and CXCL8 by ovarian cancer cells, which recruits {gamma}{delta} T cells through the chemokine receptors CXCR1 and CXCR2, to enhance the cytotoxicity of {gamma}{delta} T cells. Metabolomics analysis discovered compounds that are responsible for the enhancement of {gamma}{delta} T cell cytotoxicity, one of which follows the aforementioned mechanism, while other compounds reflect undiscovered mechanisms. Overall, we presented the positive side of the malignant ascites in anti-tumor immunity, revealed the underlining mechanisms and at least partially interpreted the molecular basis. Our work thus provides new insights into the development of cell therapies for ovarian cancer.

immunology↗

Investigation of the Mechanism of Action of JinHuangJieDu against SARS-CoV-2 Infection and Inflammation Based on Network Pharmacology and Experimental Validation

Withdrawal StatementThe authors have withdrawn this manuscript because additional experiments are required to enhance the completeness and clarity of the study. Therefore, the authors do not wish this work to be cited as a reference for any project. If you have any questions, please contact the corresponding author at lcchenlong@163.com.

cell biology↗

Preventing large deletions and chromosome loss in engineered human primary T cells by CasPlus with optimized guide RNAs

Genetically engineered T-cell therapies rely heavily on genome editing tools, such as the CRISPR/Cas9 system. However, unintended on-target chromosomal alterations, including large deletions and chromosome loss can occur and pose significant risks including tumorigenesis. Here we combined CasPlus and optimized guide RNAs to reduce these issues in CRISPR/Cas9 engineering human primary T cells. CasPlus, which integrates an engineered T4 DNA polymerase with Cas9 nuclease and guide RNA, promotes favorable small insertions (1-2 bp) while reducing large deletions and chromosome loss in T cells. Our optimized guide RNAs favoring small insertions reduced large deletions and chromosome loss by two- to five-fold versus those favoring small deletions. Moreover, combining optimized guide RNA with T4 DNA polymerase further synergistically reduced large deletions and chromosome loss by additional two-fold. Notably, replacing currently used guide RNA pairs in clinically applications with optimized pairs biased towards small insertions, along with CasPlus instead of Cas9, for editing greatly reduced large deletions and chromosome loss in gene-edited human primary T cells. These findings demonstrated that pre-selecting target sites favoring small insertions via guide RNA optimization coupled with CasPlus editing is a safer and more effective strategy to improve genome stability in T-cell engineering and other gene-editing applications.

bioengineering↗

Identification and predictive machine learning models construction of gut microbiota associated with lymph node metastasis in colorectal cancer

This study focuses on the significant role between gut microbiota and lymph node metastasis (LNM) in colorectal cancer (CRC). By conducting 16S rRNA sequencing on fecal samples from 147 CRC patients and combining it with the linear discriminant analysis effect size (LEfSe) algorithm, we successfully identified significant differences in the gut microbiota between patients with LNM and those with none lymph node metastasis (NLNM). Furthermore, using transcriptome data from 9 CRC patients, we constructed an immune cell infiltration matrix to deeply explore the biological functions associated with LNM. Eventually, using the characteristics of the gut microbiota associated with LNM, we developed random forest (RF) and multilayer perceptron (MLP) machine learning models to predict the lymph node metastasis status of CRC patients. We identified 21 differentially abundant gut microbes between the two groups, among which Bacteroides plebeius, significantly enriched in LNM group, is closely related to the upregulation of resting NK cells and chemokine CXCL8 expression, and this bacterial species is also positively correlated with the enhancement of fructose metabolism. The RF and MLP models constructed based on the LNM-associated gut microbiota showed good predictive efficacy in predicting LNM status in CRC. This study reveals that Bacteroides plebeius may play an important role in the progression of CRC, with its mechanism potentially involving changes in immune modulation and metabolic pathways. The classification model constructed based on gut microbiota characteristics can predict LNM status of CRC, providing a new perspective for personalized and precision treatment of CRC patients. ImportanceThis study highlights the pivotal role of gut microbiota in lymph node metastasis (LNM) of CRC, identifying key microbial differences between LNM and NLNM patients. Our findings implicate Bacteroides plebeius in CRC progression via immune modulation and metabolic alterations. Moreover, machine learning models based on gut microbiota predict LNM status accurately, offering a novel approach for personalized CRC treatment.

microbiology↗

DNA spontaneously wrapping around a histone core prefers negative supercoiling: A Brownian dynamics study

In eukaryotes, DNA achieves a highly compact structure primarily due to its winding around the histone cores. The nature wrapping of DNA around histone core form a 1.7 left-handed superhelical turns, contributing to negative supercoiling in chromatin. On the contrary, negative supercoils generated behind the polymerase during transcription may play a role in triggering nucleosome reassembly. To elucidate how supercoils influence the dynamics of wrapping of DNA around the histone cores, we developed a novel model to simulate the intricate interplay between DNA and histone. Our simulations revealed that both positively and negatively supercoiled DNAs are capable of wrapping around histone cores to adopt the nucleosome conformation. Most of all, our findings confirmed a preference for negative supercoiled DNA during nucleosome wrapping, and revealed that the both of the negative writhe and twist are comparatively beneficial to the formation of the DNA wrapping around histone. This advancement in the understanding of spontaneously nucleosome formation may provide insights into the intricate dynamics of chromatin assembly and its diverse functions. Our model thus can be further utilized to simulate the formations of multi-nucleosomes during re-assembling of the chromatin fiber, which will significantly enhance the understanding of the fundamental mechanisms governing the structure and function of chromatin. Author summaryThe compacted organization of DNA within chromatin is primarily attributed to its intricate winding around histone cores. This winding process involves 1.7 left-handed superhelical turns around the histone core, contributing to the negative supercoiling within chromatin fibers. To gain deeper insights into how DNA supercoiling impacts the dynamics of DNA wrapping around histone cores, we devised a novel computational model that simulates the intricate interplay between DNA and histone cores. Additionally, our simulations revealed that both of the positively and negatively supercoiled DNA can spontaneously adopt the nucleosome conformation upon wrapping around the histone core, and demonstrated a preferential tendency for negative supercoiling during nucleosome wrapping. Finally, we examined that both the negative writhe and twist components are comparatively advantageous for the formation of the nucleosome. The studies shed light on the intricate dynamics underlying chromatin assembly and its functional implications.

biophysics↗

Cross-reactivity of rPvs48/45, a recombinant Plasmodium vivax protein, with sera from Plasmodium falciparum endemic areas of Africa

BackgroundPs48/45, a Plasmodium gametocyte surface protein, is a promising candidate for malaria transmission-blocking (TB) vaccine. Due to its relevance for a multispecies vaccine, we explored the cross-reactivity and TB activity of a recombinant P. vivax Ps48/45 protein (rPvs48/45) with sera from P. falciparum-exposed African donors. MethodsrPvs48/45 was produced in Chinese hamster ovary cell lines and tested by ELISA for its cross-reactivity with sera from Burkina Faso, Tanzania, Mali, and Nigeria - In addition, BALB/c mice were immunized with the rPvs48/45 protein formulated in Montanide ISA-51 and inoculated with a crude extract of P. falciparum NF-54 gametocytes to evaluate the parasite-boosting effect on rPvs48/45 antibody titers. Specific anti-rPvs48/45 IgG purified from African sera was used to evaluate the ex vivo TB activity on P. falciparum, using standard mosquito membrane feeding assays (SMFA). ResultsrPvs48/45 protein showed cross-reactivity with sera of individuals from all four African countries, in proportions ranging from 94% (Tanzania) to 40% (Nigeria). Also, the level of cross-reactive antibodies varied significantly between countries (p<0.0001), with a higher antibody level in Mali and the lowest in Nigeria. In addition, antibody levels were higher in adults ([&ge;] 17 years) than young children ([&le;] 5 years) in both Mali and Tanzania, with a higher proportion of responders in adults (90%) than in children (61%) (p<0.0001) in Mali, where male (75%) and female (80%) displayed similar antibody responses. Furthermore, immunization of mice with P. falciparum gametocytes boosted anti-Pvs48/45 antibody responses, recognizing P. falciparum gametocytes in indirect immunofluorescence antibody test. Notably, rPvs48/45 affinity-purified African IgG exhibited a TB activity of 61% against P. falciparum in SMFA. ConclusionAfrican sera (exposed only to P. falciparum) cross-recognized the rPvs48/45 protein. This, together with the functional activity of IgG, warrants further studies for the potential development of a P. vivax and P. falciparum cross-protective TB vaccine.

immunology↗

CCDC113 stabilizes sperm axoneme and head-tail coupling apparatus to ensure male fertility

The structural integrity of the sperm is crucial for male fertility, defects in sperm head-tail linkage and flagellar axoneme are associated with acephalic spermatozoa syndrome (ASS) and the multiple morphological abnormalities of the sperm flagella (MMAF). Notably, impaired head-tail coupling apparatus (HTCA) often accompanies defects in the flagellum structure, however, the molecular mechanisms underlying this phenomenon remain elusive. Here, we identified an evolutionarily conserved coiled-coil domain-containing (CCDC) protein, CCDC113, and found the disruption of CCDC113 produced spermatozoa with disorganized sperm flagella and HTCA, which caused male infertility. Further analysis revealed that CCDC113 could bind to CFAP57 and CFAP91, and function as an adaptor protein for the connection of radial spokes, nexin-dynein regulatory complex (N-DRC) and doublet microtubules (DMTs) in the sperm axoneme. Moreover, CCDC113 was identified as a structural component of HTCA, collaborating with SUN5 and CENTLEIN to connect sperm head to tail during spermiogenesis. Together, our studies reveal that CCDC113 serve as a critical hub for sperm axoneme and HTCA stabilization, providing insights into the potential pathogenesis of infertility associated with human CCDC113 mutations.

developmental biology↗

Glia-derived secretory fatty acid binding protein Obp44a regulates lipid storage and efflux in the developing Drosophila brain

Glia derived secretory factors play diverse roles in supporting the development, physiology, and stress responses of the central nervous system (CNS). Through transcriptomics and imaging analyses, we have identified Obp44a as one of the most abundantly produced secretory proteins from Drosophila CNS glia. Protein structure homology modeling and Nuclear Magnetic Resonance (NMR) experiments reveal Obp44a as a fatty acid binding protein (FABP) with a high affinity towards long-chain fatty acids in both native and oxidized forms. Further analyses demonstrate that Obp44a effectively infiltrates the neuropil, traffics between neuron and glia, and is secreted into hemolymph, acting as a lipid chaperone and scavenger to regulate lipid and redox homeostasis in the developing brain. In agreement with this essential role, deficiency of Obp44a leads to anatomical and behavioral deficits in adult animals and elevated oxidized lipid levels. Collectively, our findings unveil the crucial involvement of a noncanonical lipid chaperone to shuttle fatty acids within and outside the brain, as needed to maintain a healthy brain lipid environment. These findings could inspire the design of novel approaches to restore lipid homeostasis that is dysregulated in CNS diseases.

developmental biology↗

Resting natural killer cells promote the progress of colon cancer liver metastasis by elevating tumor-derived sSCF

PurposeThe abundance and biological contribution of Natural killer (NK) cells in cancer are controversial. Here, we aim to uncover clinical relevance and cellular roles of NK cells in colon cancer liver metastasis (CCLM) MethodsWe integrated single-cell RNA sequencing, spatial transcriptomics, and bulk RNA-sequencing datasets to investigate NK cells biological properties and functions in the microenvironment of primary and liver metastatic tumors. Results were validated through an in vitro co-culture experiment based on bioinformatics analysis. ResultsWe used single-cell RNA sequencing and spatial transcriptomics to map the immune cellular landscape of colon cancer and well-matched liver metastatic cancer. We discovered that GZMK+ resting NK cells increased significantly in tumor tissues and were enriched in the tumor regions of both diseases. After combining bulk RNA and clinical data, we observed that these NK cell subsets contributed to a worse prognosis. Meanwhile, KIR2DL4+ activated NK cells exhibited the opposite position and relevance. Pseudotime cell trajectory analysis revealed the evolution of activated to resting NK cells. In vitro experiments further confirmed that tumor-cell-co-cultured NK cells exhibited a decidual-like status, as evidenced by remarkable increasing CD9 expression. Functional experiments finally revealed that NK cells exhibited tumor-activating characteristics by promoting the dissociation of SCF (stem cell factor) on the tumor cells membrane depending on cell-to-cell interaction, as the supernatant of the co-culture system enhanced tumor progression. ConclusionTogether, our findings revealed a population of protumorigenic NK cells that may be exploited for novel therapeutic strategies to improve therapeutic outcomes for patients with CCLM.

immunology↗

Modeling and Correction of Protein Conformational Disease in iPSC-derived Neurons through Personalized Base Editing

AbstractAltered protein conformation can cause incurable neurodegenerative disorders. Mutations in SERPINI1, the gene encoding neuroserpin, can alter protein conformation resulting in cytotoxic aggregation leading to neuronal death. Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is a rare autosomal dominant progressive myoclonic epilepsy that progresses to dementia and premature death. We developed HEK293T and induced pluripotent stem cell (iPSC) models of FENIB, harboring a patient-specific pathogenic SERPINI1 variant or stably overexpressing mutant neuroserpin fused to GFP (MUT NS-GFP). Here, we utilized a personalized adenine base editor (ABE)-mediated approach to correct the pathogenic variant efficiently and precisely to restore neuronal dendritic morphology. ABE-treated MUT NS-GFP cells demonstrated reduced inclusion size and number. Using an inducible MUT NS-GFP neuron system, we identified early prevention of toxic protein expression allowed aggregate clearance, while late prevention halted further aggregation. To address several challenges for clinical applications of gene correction, we developed a neuron-specific engineered virus-like particle to optimize neuronal ABE delivery, resulting in higher correction efficiency. Our findings provide a targeted strategy which may treat FENIB and potentially other neurodegenerative diseases due to altered protein conformation such as Alzheimers and Huntingtons diseases.

molecular biology↗

EfNST: A composite scaling network of EfficientNet for improving spatial domain identification performance

Spatial Transcriptomics (ST) leverages Gene Expression Profiling while preserving Spatial Location and Histological Images, enabling it to provide new insights into tissue structure, tumor microenvironment, and biological development. The identification of spatial domains serves as not only the foundation for ST research but also a crucial step in various downstream analyses. However, accurately identifying spatial domains using computational methods remains a tremendous challenge due to the poor computational performance of many existing algorithms. Here, we propose EfNST, a deep learning algorithm based on a composite scaling network of the EfficientNet Network, designed specifically for the analysis of 10X Visium spatial transcriptomics data. We applied EfNST to three different datasets: human Dorsolateral Prefrontal Cortex, human breast cancer and mouse brain anterior. EfNST outperforms five advanced competing algorithms, achieving the best Adjusted Rand Index (ARI) scores of 0.554, 0.607, and 0.466, respectively. Notably, EfNST demonstrated high accuracy in identifying fine tissue structure and discovering corresponding marker genes with an improved running speed. In conclusion, EfNST offers a novel approach for inferring spatial organization of cells from discrete datapoints, facilitating the exploration of new insights in this field.

bioinformatics↗