Biology subjects

Liu, N.

Publications and source records attributed to Liu, N..

At least 91 records · Page 5Linked to original sources

bioRxiv2024

Shared and Unique Neural Codes for Biological Motion Perception in Humans and Macaque Monkeys

Throughout evolution, living organisms have honed the ability to swiftly recognize biological motion (BM) across species. However, how the brain processes within- and cross-species BM, and the evolutionary progression of these processes, remain unclear. To investigate these questions, we examined brain activity in the lateral temporal areas of humans and monkeys as they passively observed upright and inverted human and macaque BM stimuli. In humans, the middle temporal area (hMT+) responded to both human and macaque BM stimuli, while the right posterior superior temporal sulcus (pSTS) exhibited selective responses to human BM stimuli. This selectivity was evidenced by an increased feedforward connection from hMT+ to pSTS during the processing of human BM stimuli. In monkeys, the MT region processed BM stimuli from both species, but no subregion in the STS anterior to MT was specific to conspecific BM stimuli. A comparison of these findings suggests that upstream brain regions (i.e., MT) may retain homologous functions across species, while downstream brain regions (i.e., STS) may have undergone differentiation and specialization throughout evolution. These results provide insights into the commonalities and differences in the specialized visual pathway engaged in processing within- and cross-species BMs, as well as their functional divergence during evolution.

neuroscience↗

bioRxiv2024

Polymerization of Tspan7 into Helical Transmembrane Skeletons for Membrane Tether Stabilization

Tubular cell membrane protrusions, such as filopodia1, dendrites2, tunneling nanotubes (TNTs)3 and retraction fibers4, are prevalent on the cell surface. They play crucial roles in various physiological processes and disease states, including angiogenesis, wound healing, and cancer metastasis5-7. The shaping and stabilization of these protrusions are crucial for their function, and the molecular machineries involved have long been an active area of investigation. Here we employed an integrative approach combining live-cell imaging, in vitro reconstitution, and in situ cryo-EM analysis to reveal that the transmembrane protein tetraspanin 7 (TSPAN7) senses membrane curvature and polymerizes into a helical configuration on highly curved tubular membranes. These spirals act as a "transmembrane skeleton", effectively maintaining the structural integrity of membrane protrusions under mechanical stress. Our findings reveal a previously unreported assembly strategy for transmembrane proteins and a mechanism for maintaining tubular membrane protrusions.

cell biology↗

bioRxiv2024

The continuous differentiation of multiscale structural gradients from childhood to adolescence correlates with the maturation of cortical morphology and functional specialization

From childhood to adolescence, the structural organization of the human brain undergoes dynamic and regionally heterogeneous changes across multiple scales, from synaptic pruning to the reorganization of large-scale anatomical wiring. However, during this period, the developmental process of multiscale structural architecture, its association with cortical morphological changes, and its role in the maturation of functional organization remain largely unknown. Here, we utilized a longitudinal multimodal imaging dataset including 276 children aged 6 to 14 years to investigate the developmental process of multiscale cortical wiring. We used an in vivo model of cortical wiring that combines features of white matter tractography, cortico-cortical proximity, and microstructural similarity to construct a multiscale brain structural connectome. By employing the gradient mapping method, the gradient space derived from the multiscale structural connectome effectively recapitulated the sensory-association axis and anterior-posterior axis. Our findings revealed a continuous expansion of the multiscale structural gradient space during development, with the principal gradient increasingly distinguishing between primary and transmodal regions. This age-related differentiation coincided with regionally heterogeneous changes in cortical morphology. Furthermore, our study revealed that developmental changes in coupling between multiscale structural and functional connectivity were correlated with functional specialization refinement, as evidenced by changes in the participation coefficient. We also found that the differentiation of the principal multiscale structural gradient was associated with improved cognitive abilities, such as enhanced working memory and attention performance, and potentially supported by molecular processes related to synaptic functions. These findings advance our understanding of the intricate maturation process of brain structural organization and its implications for cognitive performance.

neuroscience↗

bioRxiv2024

Epithelial NSD2 maintains FMOs-mediated taurine biosynthesis to prevent intestinal barrier disruption

Inflammatory bowel disease (IBD) poses a significant challenge due to its intricate pathogenesis. NSD2, a histone methyltransferase responsible for dimethylating histone 3 at lysine 36, is associated with transcriptional activation. However, the precise role of NSD2 in IBD remains unexplored. In this study, we discovered a downregulation of NSD2 in both the intestinal epithelial cells (IECs) of patients and the IBD mouse model. Deficiency of NSD2 in mouse IECs aggravated epithelial barrier disruption and inflammatory response in IBD. Mechanically, NSD2 loss downregulated H3K36me2 and FMO (taurine-synthesis enzyme) mRNA in IECs, resulting in decreased taurine biosynthesis in IECs. Importantly, supplementation with taurine significantly attenuated the symptoms of NSD2 deficiency-induced IBD. These data demonstrate that NSD2 plays a pivotal role in maintaining FMOs-mediated taurine biosynthesis to prevent intestinal inflammation. Our findings also underscore the importance of NSD2-H3K36me2-mediated taurine biosynthesis in maintaining intestinal mucosal barrier homeostasis.

cell biology↗

bioRxiv2024

Opto-chemogenetic inhibition of L-type CaV1 channels in neurons through a membrane-assisted molecular linkage

Acute, specific, and robust inhibition of L-type Ca2+ (CaV1) channels has been sought after for both research and therapeutic applications. Compared to other available CaV1 antagonists, genetically-encoded modulators, such as CMI (C-terminus mediated inhibition) peptides encoded by CaV1 DCT (distal C-terminus), hold great potentials due to its affirmative mechanisms of action on both gating and signaling. Here, we find that membrane-anchoring with a Ras tag could essentially help form a type of intramolecular-equivalent linkage, by which the tag anchored-peptide appears to dimerize with another protein or peptide on the membrane, supported by the evidence from patch-clamp electrophysiology and FRET imaging. We then design and implement the constitutive and inducible CMI modules, with appropriate dynamic ranges targeting the short and long variants of CaV1.3, both naturally occurring in neurons. Upon optical (infrared-responsive nanoparticles) and/or chemical (rapamycin) induction of FRB/FKBP binding, DCT peptides with no CMI in the cytosol acutely translocate onto the membrane via FRB-Ras, where the physical linkage requirement could be fulfilled. The peptides robustly produce acute and potent inhibitions on both recombinant CaV1.3 channels and neuronal CaV1 activities, and thus the Ca2+ influx-neuritogenesis coupling. Validated through opto-chemogenetic induction, this prototype demonstrates channel modulation via membrane-assisted molecular linkage, promising broad applicability to diverse membrane proteins.

bioengineering↗

bioRxiv2024

Intestinal microbiome dysbiosis increases Mycobacteria pulmonary colonization in mice by regulating the Nos2-associated pathways

AbstractIncreasing researches reveal gut microbiota was associated with the development of tuberculosis. How to prevent or reduce Mycobacterium tuberculosis colonization in the lungs is a key measure to prevent tuberculosis. However, the data on gut microbiota preventing Mycobacterium colonization in the lungs were scarce. Here, we established the clindamycin-inducing intestinal microbiome dysbiosis and fecal microbial transplantation models in mice to identify gut microbiotas effect on Mycobacteriums colonization in the mouse lungs and explore its potential mechanisms. The results showed that clindamycin treatment altered the diversity and composition of the intestinal bacterial and fungal microbiome, weakened the trans-kingdom network interactions between bacteria and fungi, and induced gut microbiome dysbiosis in the mice. Gut microbiota dysbiosis increases intestinal permeability and enhances the susceptibility of Mycobacterium colonization in the lungs of mice. The potential mechanisms were gut microbiota dysbiosis altered the lung transcriptome and increased Nos2 expression through the "gut-lung axis". Nos2 high expression disrupts the intracellular antimicrobial and anti-inflammatory environment by increasing the concentration of NO, decreasing the levels of ROS and Defb1 in the cells, and resulting in promoting Mycobacteria colonization in the lungs of mice. The present study raises a potential strategy for reducing the risks of Mycobacteria infections and transmission by regulating the gut microbiome balance.

microbiology↗

bioRxiv2024

Development of the overlapping network modules in the human brain

Developmental connectomic studies have shown that the modular organization of functional networks in the human brain undergoes substantial reorganization with age to support cognitive growth. However, these studies implicitly assume that each brain region belongs to one and only one specific network module, ignoring the potential spatial overlap between functional modules. How the overlapping functional modular architecture develops and whether this development is related to structural signatures remain unknown. Using longitudinal multimodal structural, functional, and diffusion MRI data from 305 children (aged 6-14 years), we investigated the development of the overlapping modular architecture of functional networks, and further explored their structural associations. Specifically, an edge-centric network model was used to identify the overlapping functional modules, and the nodal overlap in module affiliations was quantified using the entropy measure. We showed a remarkable regional inhomogeneity in module overlap in children, with higher entropy in the ventral attention, somatomotor, and subcortical networks and lower entropy in the visual and default-mode networks. Furthermore, the overlapping modules developed in a linear, spatially dissociable manner from childhood to adolescence, with significantly reduced entropy in the prefrontal cortex and putamen and increased entropy in the parietal lobules. Personalized overlapping modular patterns capture individual brain maturity as characterized by brain age. Finally, the overlapping functional modules can be significantly predicted by integrating gray matter morphology and white matter network properties. Our findings highlight the maturation of overlapping network modules and their structural substrates, thereby advancing our understanding of the principles of connectome development.

neuroscience↗

bioRxiv2024

Haplotype-resolved genomes and population genetics to analyze glandular secretory trichome formation mechanism in oregano

Oregano is an important economic plant which has valuable medicinal and aromatic properties. Oregano essential oil, containing carvacrol and thymol, is a preferred material to replace antibiotics in feed additives. Glandular secretory trichome (GST) density has positively correlated with the production of these compounds. Here, two haplotype-resolved genomes were assembled and annotated which contained 15 chromosomes with the total length of 606.75 and 612.74 Mb, respectively. Oregano had experienced two whole-genome duplications corresponding to the divergence [~]5.120/4.564 and [~]66.857/69.923 Mya, respectively. Many transcription factors and genes were found related to GSTs formation mechanism such as R2R3-MYB- and HD-ZIP IV-encoding genes. 2,669,410 SNPs, 569,093 InDels, 14,839 DUPs, 110 INVs, 3,976 TRANSs, and 1,426 CNVs were detected among two haplotype-resolved genomes. Two high density genetic linkage maps consisted of 15 LGs and spanned 2,279.28 and 2,322.83 cM, respectively. GADS, GABS, and GTS of F2 segregating populations showed obvious superparental dominance. One/one, one/one, and two/four QTLs for GADS, GABS, and GTS were independently mapped on two genetic maps, respectively. Five candidate genes showed extreme difference in two bulked segregant pools. Our study not only provides significant insight into the GSTs formation mechnism, but also will facilitate molecular breeding in oregano. One Sentence SummaryOregano essential oil is a preferred material to replace antibiotics which will use to study the glandular secretory trichome formation mechanism and analyze the source of essential oil.

genetics↗

bioRxiv2024

hoodscanR: profiling single-cell neighborhoods in spatial transcriptomics data

Understanding complex cellular niches and neighborhoods have provided new insights into tissue biology. Thus, accurate neighborhood identification is crucial, yet existing methodologies often struggle to detect informative neighborhoods and generate cell-specific neighborhood profiles. To address these limitations, we developed hoodscanR, a Bioconductor package designed for neighborhood identification and downstream analyses using spatial data. Applying hoodscanR to breast and lung cancer datasets, we showcase its efficacy in conducting detailed neighborhood analyses and identify subtle transcriptional changes in tumor cells from different neighborhoods. Such analyses can help researchers gain valuable insights into disease mechanisms and potential therapeutic targets.

bioinformatics↗

bioRxiv2024

Have AI-Generated Texts from LLM Infiltrated the Realm of Scientific Writing? A Large-Scale Analysis of Preprint Platforms

Since the release of ChatGPT in 2022, AI-generated texts have inevitably permeated various types of writing, sparking debates about the quality and quantity of content produced by such large language models (LLM). This study investigates a critical question: Have AI-generated texts from LLM infiltrated the realm of scientific writing, and if so, to what extent and in what setting? By analyzing a dataset comprised of preprint manuscripts uploaded to arXiv, bioRxiv, and medRxiv over the past two years, we confirmed and quantified the widespread influence of AI-generated texts in scientific publications using the latest LLM-text detection technique, the Binoculars LLM-detector. Further analyses with this tool reveal that: (1) the AI influence correlates with the trend of ChatGPT web searches; (2) it is widespread across many scientific domains but exhibits distinct impacts within them (highest: computer science, engineering sciences); (3) the influence varies with authors who have different language speaking backgrounds and geographic regions according to the location of their affiliations (Italy, China, etc.); (4) AI-generated texts are used in various content types in manuscripts (most significant: hypothesis formulation, conclusion summarization); (5) AI usage has a positive influence on papers impact, measured by its citation numbers. Based on these findings, suggestions about the advantages and regulation of AI-augmented scientific writing are discussed.

scientific communication and education↗

bioRxiv2024

Normative growth modeling of brain morphology reveals neuroanatomical heterogeneity and biological subtypes in children with ADHD

BackgroundNeuroimaging studies suggest substantial individual heterogeneity in brain phenotypes in attention-deficit/hyperactivity disorder (ADHD). However, how these individual-level brain phenotypes contribute to the identification of ADHD biotypes and whether these biotypes have different treatment outcomes and neurobiological underpinnings remain largely unknown. MethodsWe collected multisite, high-quality structural magnetic resonance imaging data from 1,006 children aged 6-14 years, including 351 children with ADHD and 655 typically developing children. Normative growth models of cortical thickness were established for 219 regions in the typically developing children. Individual-level deviations from these normal references were quantified and clustered to identify ADHD biotypes. We validated the replicability and generalizability of the ADHD biotypes using two independent datasets and evaluated the associations of the biotypes with symptomatic, cognitive, and gene expression profiles, as well as follow-up treatment outcomes. FindingsNo more than 10% of children with ADHD had extreme deviations in cortical thickness in a single region, suggesting high heterogeneity among individuals with ADHD. On the basis of the brain deviation maps, we discovered two robust ADHD biotypes, an infra-normal subtype with cortical thinning associated with ADHD symptoms and a supranormal subtype with cortical thickening associated with cognition. Patients with the infra-normal subtype responded better to methylphenidate than to atomoxetine, although both subtypes showed treatment efficacy. Brain deviations in the infra-normal subtype were explained by the expression levels of genes enriched in presynaptic and axonal development and polygenic risk of ADHD. InterpretationWe identified anatomically distinct, clinically valuable, and biologically informed ADHD subtypes, providing insight into the neurobiological basis of clinical heterogeneity and facilitating a personalized medication strategy for ADHD patients. Panel: Research in contextO_ST_ABSEvidence before this studyC_ST_ABSSubstantial individual heterogeneity in brain phenotypes in attention-deficit/hyperactivity disorder (ADHD) motivates the need to discover homogeneous biotypes. We searched PubMed for research articles on ADHD biotypes using brain MRI published before December 1, 2023, using the search terms ((attention deficit hyperactivity disorder [Title/Abstract]) OR (ADHD [Title/Abstract])) AND ((subtypes [Title/Abstract]) OR (subgroups [Title/Abstract]) OR (subtyping [Title/Abstract])) AND ((MRI [Title/Abstract]) OR (neuroimaging [Title/Abstract]) OR (brain [Title/Abstract])) without language restrictions. Of the eight included studies, two identified ADHD biotypes using structural morphology, four used functional activity, and two used multimodal features. However, none of these studies considered the developmental effect of the brain phenotypes, examined treatment response, or investigated the genetic correlates of the biotypes. Added value of this studyThis study is the first to use individualized brain measures extracted from normative models to investigate ADHD biotypes in a large sample of more than 1,000 children. We identified two reproducible ADHD biotypes, characterized by distinct symptomatic, cognitive, and gene expression profiles, as well as differential treatment responses. This study advances our understanding of the neurobiological basis underlying the clinical heterogeneity of ADHD and highlights the critical need to discover ADHD biotypes using an unbiased and individualized approach. Implications of all the available evidenceThis study revealed remarkable neuroanatomical heterogeneity in ADHD patients and identified anatomically distinct, clinically valuable, and biologically informed ADHD biotypes. Our findings have potential value for the investigation of data-driven biotypes to evaluate treatment efficacy and facilitate personalized treatment. We also highlight the need for future studies to move beyond the understanding of ADHD solely based on the "average patient" perspective.

neuroscience↗

bioRxiv2024

Granzyme B-based CAR T cells block metastasis by eliminating circulating tumor cells

Chimeric antigen receptor (CAR) T cells have limited efficacy against solid tumors due to the hostile microenvironment. Circulating tumor cells (CTCs) are essential to metastasis, which is the cause of most of cancer-related death. Here, we generated GrB-CAR T cells targeting membrane-bound HSP70 (mHSP70), a highly tumor-specific antigen detected in numerous cancers. GrB-CAR T cells exhibited potent cytotoxicity against a broad spectrum of cancer cell lines and stem-like cancer cells in vitro and effectively inhibited xenograft tumor growth in vivo. Importantly, GrB-CAR T cells markedly decreased the number of CTCs and, therefore, hindered cancer metastasis in spontaneous metastasis models with uncontrollable primary tumor growth, a scenario commonly encountered in clinical trials of CAR T therapies for solid tumors. Furthermore, despite the 100% homology between human and macaque HSP70 protein, the autotransplantation of macaque T cells expressing human GrB-CAR did not cause any obvious toxic effects. These results not only demonstrate GrB-CAR T cells as a safe and effective tactic with broad-spectrum anticancer activity, but also offer strong experimental evidence and proof-of-concept validation for CAR T cell-mediated metastasis inhibition by targeting CTCs.

immunology↗

bioRxiv2024

Cell-cycle and Age-Related Modulations in Mouse Chromosome Stiffness

Chromosome structure is complex, and many aspects of chromosome organization are still not understood. Measuring the stiffness of chromosomes offers valuable insight into their structural properties. In this study, we analyzed the stiffness of chromosomes from metaphase I (MI) and metaphase II (MII) oocytes. Our results revealed a ten-fold increase in stiffness (Youngs modulus) of MI chromosomes compared to somatic chromosomes. Furthermore, the stiffness of MII chromosomes was found to be lower than that of MI chromosomes. We examined the role of meiosis-specific cohesin complexes in regulating chromosome stiffness. Surprisingly, the stiffness of chromosomes from three meiosis-specific cohesin mutants did not significantly differ from that of wild-type chromosomes, indicating that these cohesins may not be primary determinants of chromosome stiffness. Additionally, our findings revealed an age-related increase of chromosome stiffness for MI oocytes. Since aging is associated with elevated levels of DNA damage, we investigated the impact of etoposide-induced DNA damage on chromosome stiffness and found that it led to a reduction in stiffness in MI oocytes. Overall, our study underscores the dynamic and cyclical nature of chromosome stiffness, modulated by both the cell cycle, and by age-related factors.

biophysics↗

bioRxiv2024

The segmented flavivirus Alongshan virus reduces mitochondrial mass via degrading STAT2 to suppress innate immune response

Alongshan virus (ALSV) is a newly discovered pathogen of the Flaviviridae family, characterized by a multi-segmented genome distantly related to the canonical flaviviruses. Understanding the pathogenic mechanism of the emerging segmented flavivirus is crucial for the development of intervention strategies. Here we show that ALSV can infect multiple mammalian cells and induces the expression of antiviral genes. Moreover, ALSV is sensitive to IFN-{beta} and possesses the ability to counteract type I IFN response. Mechanistically, ALSVs nonstructural protein NSP1 binds to and degrades human STAT2 through an autophagy pathway in a species-dependent manner, resulting in direct inhibition of the expression of interferon-stimulated genes (ISGs). Specifically, NSP1 methyltransferase domain binds to the key sites of F175/R176 located in coiled-coil domain of STAT2. Moreover, NSP1-mediated degradation of STAT2 results in a reduction in mitochondrial mass by disrupting mitochondrial dynamics to induce mitophagy and inhibiting mitochondrial biogenesis, thereby suppressing the innate immune response. Interestingly, inhibiting mitophagy using 3-Methyladenine and enhancing mitochondrial biogenesis using the PPAR{gamma} agonist pioglitazone can reverse NSP1-mediated inhibition of ISGs, suggesting that promoting mitochondrial mass presents an effective antiviral strategy. Our findings elucidate the intricate regulatory crosstalk between ALSV and the hosts innate immune response, providing valuable insights into the pathogenesis and intervention strategy of emerging segmented flavivirus.

microbiology↗

bioRxiv2024

Perturbing nuclear glycosylation in the mouse preimplantation embryo slows down embryonic growth

The only known form of intracellular protein glycosylation (O-GlcNAc) is reversible and has been mapped on thousands of cytoplasmic and nuclear proteins, including RNA polymerase II, transcription factors and chromatin modifiers. The O-GlcNAc modification is catalyzed by a single enzyme known as O-GlcNAc Transferase (OGT), that is required for mammalian early development. Remarkably, the regulatory function of protein O-GlcNAcylation in the embryo as well as the embryonic O-GlcNAc proteome remain unknown. Here, we devised a new method to enzymatically remove O-GlcNAc from preimplantation embryonic nuclei, where it accumulates coincidently with embryonic genome activation (EGA). Unexpectedly, the depletion of nuclear O-GlcNAc to undetectable levels has no impact on EGA, but dampens the transcriptional activation of the translational machinery, and triggers a spindle checkpoint response. These molecular alterations were phenotypically associated with a developmental delay starting from early cleavage stages and persisting after embryo implantation, establishing a novel link between nuclear glycosylation and embryonic growth.

developmental biology↗

bioRxiv2024

Relaxed selection and horizontal gene transfer fuel underwater adaptation in a water spider

Spiders have primarily adapted to terrestrial life, yet a number of species have made evolutionary transitions to marine and freshwater environments. While its physiological and behavioral adaptations have been characterized, the genetic basis of semi-aquatic and aquatic adaptation in spiders remains poorly understood. Here, we provide a high-quality, chromosome-level genome assembly for the aquatic spider Argyroneta aquatica, alongside a reference transcriptome for the semi-aquatic spider Desis martensi. We performed comparative genomes analyses of 22 spider species, including a unique aquatic spider, two semi-aquatic spiders and 19 terrestrial spider species, with a focus on those in the marronoid clade. By integrating morphological, phylogenomic, comparative genomic, transcriptomic, and metabolomic analyses, we explored the genomic adaptations of aquatic and semi-aquatic spiders. Phylogenomic analysis suggests that aquatic and semi-aquatic spiders have independently evolved from their terrestrial ancestors and represent divergent evolutionary routes We found hundreds of genes tend to experience relaxed selection, positive selection, and evidence of horizontal gene transfer (HGT) associated with the transition to aquatic and semi-aquatic life in spiders. These genes are associated with respiratory, osmoregulatory, fat metabolism and digestion, hypoxia, and thermal functions, putatively facilitate the adaptations to diverse underwater life. Altogether, our findings highlight the divergent evolutionary mechanisms enabling spiders to thrive in diverse aquatic environments, providing insights into the genomic basis of adaptations to semi-aquatic and aquatic habitats.

genomics↗

bioRxiv2024

Development of deaminase-free T-to-S base editor and C-to-G base editor by engineered human uracil DNA glycosylase

DNA base editors could enable direct editing of adenine (A), cytosine (C), or guanine (G), but there is no base editor for direct thymine (T) editing currently. Here, by fusing Cas9 nickase (nCas9) with engineered human uracil DNA glycosylase (UNG) variants, we developed a deaminase-free glycosylase-based thymine base editor (gTBE) with the ability of direct T editing. By several rounds of UNG mutagenesis via rational screening, we demonstrated that gTBE with engineered UNG variants could achieve T editing efficiency by up to 81.5%. Furthermore, the gTBE exhibited high T-to-S (i.e., T-to-C or T-to-G) conversion ratio with up to 0.97 in cultured human cells. Using similar strategy, we developed a deaminase-free cytosine base editor (gCBE) facilitating specifically direct C editing by engineered UNG with mutations different from gTBE. Thus, we provide two novel base editors, gTBE and gCBE, with corresponding engineered UNG variants, broadening the targeting scope of base editors.

molecular biology↗

bioRxiv2023

Predicting biomarker for the acute pulmonary embolism by using gene ontology and machine learning

Key PointsEarly and Accurate Diagnosis Essential: Acute pulmonary embolism (PE) is a critical condition that demands prompt and precise diagnosis for effective treatment. Limitations of Current Diagnostics: Existing diagnostic methods like Computed Tomography Pulmonary Angiography (CTPA) have certain limitations, leading to the exploration of alternative approaches. Potential of Blood-Based Biomarkers: A recent study focused on identifying blood-based biomarkers for PE. This involved using gene ontology analysis and machine learning methods to analyze gene expression data from both PE patients and healthy controls. Gene Selection and Analysis: The study selected 20 genes for detailed analysis. These included various coagulation factors, fibrinolytic genes, and inflammation markers. Gene Ontology enrichment analysis was performed to understand the biological processes and molecular functions of these genes. Machine Learning for Diagnosis: Supervised machine learning algorithms were utilized to create classification models using the expression levels of these 20 genes. The models demonstrated promising results in distinguishing PE patients from healthy individuals. Acute pulmonary embolism (PE) is a life-threatening condition requiring early and accurate diagnosis. Current diagnostic methods like CTPA have limitations, and a study aimed to identify potential blood-based biomarkers for PE using gene ontology analysis and machine learning methods. Gene expression data of PE patients and healthy controls were obtained from the Gene Expression Omnibus database. A total of 20 genes were selected for further analysis, including coagulation factors F7, F10, F12, fibrinolytic genes PLAT, SERPINE1 and SERPINE2, and inflammation markers SELE, VCAM1 and ICAM. Gene Ontology enrichment analysis was performed to identify biological processes and molecular functions overrepresented among the candidate genes. Supervised machine learning algorithms were applied to build classification models using the expression levels of the 20 genes as features. Nested cross-validation was employed to assess model performance. The RF model achieved the highest area under the receiver operating characteristic curve of 0.89, indicating excellent discrimination between PE patients and controls based on the gene expression signature. Validation in larger cohorts is warranted to clinically translate these findings into a non-invasive diagnostic test for PE.

genomics↗