Model Of Complex Research Articles

The structure assessment web server: for proteins, complexes and more.

The 'structure assessment' web server is a one-stop shop for interactive evaluation and benchmarking of structural models of macromolecular complexes including proteins and nucleic acids. A user-friendly web dashboard links sequence with structure information and results from a variety of state-of-the-art tools, which facilitates the visual exploration and evaluation of structure models. The dashboard integrates stereochemistry information, secondary structure information, global and local model quality assessment of the tertiary structure of comparative protein models, as well as prediction of membrane location. In addition, a benchmarking mode is available where a model can be compared to a reference structure, providing easy access to scores that have been used in recent CASP experiments and CAMEO. The structure assessment web server is available at https://swissmodel.expasy.org/assess.

Structures and dynamics of Rpd3S complex bound to nucleosome.

The Rpd3S complex plays a pivotal role in facilitating local histone deacetylation in the transcribed regions to suppress intragenic transcription initiation. Here, we present the cryo-electron microscopy structures of the budding yeast Rpd3S complex in both its apo and three nucleosome-bound states at atomic resolutions, revealing the exquisite architecture of Rpd3S to well accommodate a mononucleosome without linker DNA. The Rpd3S core, containing a Sin3 Lobe and two NB modules, is a rigid complex and provides three positive-charged anchors (Sin3_HCR and two Rco1_NIDs) to connect nucleosomal DNA. In three nucleosome-bound states, the Rpd3S core exhibits three distinct orientations relative to the nucleosome, assisting the sector-shaped deacetylase Rpd3 to locate above the SHL5-6, SHL0-1, or SHL2-3, respectively. Our work provides a structural framework that reveals a dynamic working model for the Rpd3S complex to engage diverse deacetylation sites.

Vitamin K Epoxide Reductase Complex-Protein Disulphide Isomerase Assemblies in the Thiol-Disulphide Exchange Reactions: Portrayal of Precursor-to-Successor Complexes.

The human Vitamin K Epoxide Reductase Complex (hVKORC1), a key enzyme that converts vitamin K into the form necessary for blood clotting, requires for its activation the reducing equivalents supplied by its redox partner through thiol-disulphide exchange reactions. The functionally related molecular complexes assembled during this process have never been described, except for a proposed de novo model of a 'precursor' complex of hVKORC1 associated with protein disulphide isomerase (PDI). Using numerical approaches (in silico modelling and molecular dynamics simulation), we generated alternative 3D models for each molecular complex bonded either covalently or non-covalently. These models differ in the orientation of the PDI relative to hVKORC1 and in the cysteine residue involved in forming protein-protein disulphide bonds. Based on a comparative analysis of these models' shape, folding, and conformational dynamics, the most probable putative complexes, mimicking the 'precursor', 'intermediate', and 'successor' states, were suggested. In addition, we propose using these complexes to develop the 'allo-network drugs' necessary for treating blood diseases.

Structural characterization of methylation-independent PP2A assembly guides alphafold2Multimer prediction of family-wide PP2A complexes

Dysregulation of phosphorylation-dependent signaling is a hallmark of tumorigenesis. Protein phosphatase 2 (PP2A) is an essential regulator of cell growth. One scaffold subunit (A) binds to a catalytic subunit (C) to form a core AC heterodimer, which together with one of many regulatory (B) subunits forms the active trimeric enzyme. The combinatorial number of distinct PP2A complexes is large, which results in diverse substrate specificity and subcellular localization. The detailed mechanism of PP2A assembly and regulation remains elusive and reports about an important role of methylation of the carboxy terminus of PP2A C are conflicting. A better understanding of the molecular underpinnings of PP2A assembly and regulation is critical to dissect PP2A function in physiology and disease. Here, we combined biochemical reconstitution, mass spectrometry, X-ray crystallography and functional assays to characterize the assembly of trimeric PP2A. In vitro studies demonstrated that methylation of the carboxy-terminus of PP2A C was dispensable for PP2A assembly in vitro. To corroborate these findings, we determined the X-ray crystal structure of the unmethylated PP2A Aα-B56ε-Cα trimer complex to 3.1 Å resolution. The experimental structure superimposed well with an Alphafold2Multimer prediction of the PP2A trimer. We then predicted models of all canonical PP2A complexes providing a framework for structural analysis of PP2A. In conclusion, methylation was dispensable for trimeric PP2A assembly and integrative structural biology studies of PP2A offered predictive models for all canonical PP2A complexes.

Structure-based learning to predict and model protein-DNA interactions and transcription-factor co-operativity in cis-regulatory elements.

Transcription factor (TF) binding is a key component of genomic regulation. There are numerous high-throughput experimental methods to characterize TF-DNA binding specificities. Their application, however, is both laborious and expensive, which makes profiling all TFs challenging. For instance, the binding preferences of ∼25% human TFs remain unknown; they neither have been determined experimentally nor inferred computationally. We introduce a structure-based learning approach to predict the binding preferences of TFs and the automated modelling of TF regulatory complexes. We show the advantage of using our approach over the classical nearest-neighbor prediction in the limits of remote homology. Starting from a TF sequence or structure, we predict binding preferences in the form of motifs that are then used to scan a DNA sequence for occurrences. The best matches are either profiled with a binding score or collected for their subsequent modeling into a higher-order regulatory complex with DNA. Co-operativity is modelled by: (i) the co-localization of TFs and (ii) the structural modeling of protein-protein interactions between TFs and with co-factors. We have applied our approach to automatically model the interferon-β enhanceosome and the pioneering complexes of OCT4, SOX2 (or SOX11) and KLF4 with a nucleosome, which are compared with the experimentally known structures.

Modeling of noncovalent inhibitors of the papain-like protease (PLpro) from SARS-CoV-2 considering the protein flexibility by using molecular dynamics and cross-docking.

The papain-like protease (PLpro) found in coronaviruses that can be transmitted from animals to humans is a critical target in respiratory diseases linked to Severe Acute Respiratory Syndrome (SARS-CoV). Researchers have proposed designing PLpro inhibitors. In this study, a set of 89 compounds, including recently reported 2-phenylthiophenes with nanomolar inhibitory potency, were investigated as PLpro noncovalent inhibitors using advanced molecular modeling techniques. To develop the work with these inhibitors, multiple structures of the SARS-CoV-2 PLpro binding site were generated using a molecular sampling method. These structures were then clustered to select a group that represents the flexibility of the site. Subsequently, models of the protein-ligand complexes were created for the set of inhibitors within the chosen conformations. The quality of the complex models was assessed using LigRMSD software to verify similarities in the orientations of the congeneric series and interaction fingerprints to determine the recurrence of chemical interactions. With the multiple models constructed, a protocol was established to choose one per ligand, optimizing the correlation between the calculated docking energy values and the biological activities while incorporating the effect of the binding site's flexibility. A strong correlation (R2 = 0.922) was found when employing this flexible docking protocol.

Mitochondrial respiratory supercomplexes of the yeast Saccharomyces cerevisiae.

The functional and structural relationship among the individual components of the mitochondrial respiratory chain constitutes a central aspect of our understanding of aerobic catabolism. This interplay has been a subject of intense debate for over 50 years. It is well established that individual respiratory enzymes associate into higher-order structures known as respiratory supercomplexes, which represent the evolutionarily conserved organizing principle of the mitochondrial respiratory chain. In the yeast Saccharomyces cerevisiae, supercomplexes are formed by a complex III homodimer flanked by one or two complex IV monomers, and their high-resolution structures have been recently elucidated. Despite the wealth of structural information, several proposed supercomplex functions remain speculative and our understanding of their physiological relevance is still limited. Recent advances in the field were made possible by the construction of yeast strains where the association of complex III and IV into supercomplexes is impeded, leading to diminished respiratory capacity and compromised cellular competitive fitness. Here, we discuss the experimental evidence and hypotheses relative to the functional roles of yeast respiratory supercomplexes. Moreover, we review the current models of yeast complex III and IV assembly in the context of supercomplex formation and highlight the data scattered throughout the literature suggesting the existence of cross talk between their biogenetic processes.

Boosting Neural Cognitive Diagnosis with Student’s Affective State Modeling

Cognitive Diagnosis Modeling aims to infer students' proficiency level on knowledge concepts from their response logs. Existing methods typically model students’ response processes as the interaction between students and exercises or concepts based on hand-crafted or deeply-learned interaction functions. Despite their promising achievements, they fail to consider the relationship between students' cognitive states and affective states in learning, e.g., the feelings of frustration, boredom, or confusion with the learning content, which is insufficient for comprehensive cognitive diagnosis in intelligent education. To fill the research gap, we propose a novel Affect-aware Cognitive Diagnosis (ACD) model which can effectively diagnose the knowledge proficiency levels of students by taking into consideration the affective factors. Specifically, we first design a student affect perception module under the assumption that the affective state is jointly influenced by the student's affect trait and the difficulty of the exercise. Then, our inferred affective distribution is further used to estimate the student's subjective factors, i.e., guessing and slipping, respectively. Finally, we integrate the estimated guessing and slipping parameters with the basic neural cognitive diagnosis framework based on the DINA model, which facilitates the modeling of complex exercising interactions in a more accurate and interpretable fashion. Besides, we also extend our affect perception module in an unsupervised learning setting based on contrastive learning, thus significantly improving the compatibility of our ACD. To the best of our knowledge, we are the first to unify the cognition modeling and affect modeling into the same framework for student cognitive diagnosis. Extensive experiments on real-world datasets clearly demonstrate the effectiveness of our ACD. Our code is available at https://github.com/zeng-zhen/ACD.

SCS-YOLOv5s: A cattle detection and counting method for complex breeding environment

Cattle detection and counting is one of the most important topics in the development of modern agriculture and animal husbandry. The traditional manual monitoring methods are inefficient and constrained by factors such as site. To solve the above problems, a SCS-YOLOv5 cattle detection and counting model for complex breeding scenarios is proposed. The original SPPF module is replaced in the YOLOv5 backbone network with a CSP structured SPPFCSPC. A CA (Coordinate Attention) mechanism is added to the neck network, as well as the SC (Standard Convolution) of the Neck network is replaced with a light convolution GSConv and Slim Neck is introduced, and training strategies such as multi-scale training are also employed. The experimental results show that the proposed method enhances the feature extraction ability and feature fusion ability, balances the localization accuracy and detection speed, and improves the use effect in real farming scenarios. The Precision of the improved network model is improved from 93.2% to 95.5%, mAP@0.5 is improved from 94.5% to 95.2%, the RMSE is reduced by about 0.03, and the FPS reaches 88. Compared with other mainstream algorithms, the comprehensive performance of SCS-YOLOv5 s is in a leading position, with fewer missed and false detections, and the strong robustness and generalization ability of this model are proved on multi-category public datasets. Applying the improvement ideas in this paper to YOLOv8 s also yields an increase in accuracy. The improved method in this study can greatly improve the accuracy of cattle detection and counting in complex environments, and has good real-time performance, so as to provide technical support for large-scale cattle breeding.

Traditions of maghrebi-saheli statehood and islamic radicalism in Early XXI Century

The significance of this research topic is due to the relevance of the problems of modern state-building in the public and political life of North and West Africa. The purpose of the research project is to analyze the causes and consequences of the emergence of radical movements of political Islam in the Maghreb and Sahel at the junction of the XX and XXI centuries and their connection with the shortcomings of national statehood inherent in both African regions. At the same time, the author focuses on the incompleteness of the state-building process, the weakness of institutions and the low level of justification for drawing state borders as concrete examples of such shortcomings that affected the socio-political climate in the Islamized areas adjacent to the Sahara. Based on the materials of sources and the theoretical model of regional security complexes (RSC), the author identified contradictions and diversity in the ideological and value views of the North African ruling circles, analyzed the methodological and spiritual and political foundations of the deeply rooted relationship between criminal and Islamist groups on the example of the activities of Al-Qaeda in the Islamic Maghreb (AQIM) (аn organization included in the list of terrorist organizations in theRussian Federation is mentioned) and its leaders - Abd al-Malik Drukdel, Mukhtar Belmukhtar, etc. It is proved that “Islamist internationalism” in the Maghreb and Sahel of the 2000s began to take ethnocultural forms, which was caused by the ‘network’ and ‘umbrell’a nature of the AQIM (аn organization included in the list of terrorist organizations in theRussian Federation is mentioned) structure, in which there was no centralized administrative-territorial management scheme. In addition, the distinctive features of the security policy of modern Algeria are shown and the importance of studying interregional contradictions for characterizing the geopolitical and economic reasons for the strengthening of Islamic radicalism in Africa is revealed.

Higher-order homophily on simplicial complexes

Higher-order network models are becoming increasingly relevant for their ability to explicitly capture interactions between three or more entities in a complex system at once. In this paper, we study homophily, the tendency for alike individuals to form connections, as it pertains to higher-order interactions. We find that straightforward extensions of classical homophily measures to interactions of size 3 and larger are often inflated by homophily present in pairwise interactions. This inflation can even hide the presence of anti-homophily in higher-order interactions. Hence, we develop a structural measure of homophily, simplicial homophily, which decouples homophily in pairwise interactions from that of higher-order interactions. The definition applies when the network can be modeled as a simplicial complex, a mathematical abstraction which makes a closure assumption that for any higher-order relationship in the network, all corresponding subsets of that relationship occur in the data. Whereas previous work has used this closure assumption to develop a rich theory in algebraic topology, here we use the assumption to make empirical comparisons between interactions of different sizes. The simplicial homophily measure is validated theoretically using an extension of a stochastic block model for simplicial complexes and empirically in large-scale experiments across 16 datasets. We further find that simplicial homophily can be used to identify when node features are valuable for higher-order link prediction. Ultimately, this highlights a subtlety in studying node features in higher-order networks, as measures defined on groups of size k can inherit features described by interactions of size [Formula: see text].

VAERS Vasculitis Adverse Events Retrospective Study: Etiology Model of Immune Complexes Activating Fc Receptors in Kawasaki Disease and Multisystem Inflammatory Syndromes.

Vasculitis diseases include Kawasaki disease (KD), Kawasaki disease shock syndrome (KDSS), Multisystem Inflammatory Syndrome (MIS), Henoch-Schönlein purpura (HS), or IgA vasculitis, and additional vasculitis diseases. These diseases are often preceded by infections or immunizations. Disease incidence rates are higher in children than in adults. These diseases have been extensively studied, but understanding of the disease etiology remains to be established. Many studies have failed to demonstrate an association between vasculitis diseases and vaccination; this study examines possible associations. Herein, the Vaccine Adverse Event Reporting System (VAERS) database is retrospectively examined for associations between vasculitis diseases and immunizations. For some vaccines, the number of rare cases of KD, MIS, and HS are higher than the background rates. These rare cases are predicted to occur in individuals with (1) genetic risk factors with (2) antibody titer levels above the primary immune response level. Herein, the model of humoral immune response antibodies bound to antigens (pathogen or vaccine) creating immune complexes is proposed. These immune complexes are proposed to bind Fc receptors on immune cells and platelets, resulting in cell activation and the release of inflammatory molecules including histamine and serotonin. Immune complexes and inflammatory molecules including serotonin and histamine likely trigger vasculitis. Elevated serotonin and possibly histamine drive initial vasoconstrictions, disrupting blood flow. Increased blood flow pressure from cardiac capillary vasoconstrictions is predicted to trigger coronary artery aneurysms (CAA) or lesions (CAL) in some patients. For KDSS and MIS patients, these cardiac capillary vasoconstrictions are predicted to result in ischemia followed by ventricular dysfunction. Ongoing ischemia can result in long-term cardiac damage. Cases associated with pathogens are likely to have persistent infections triggering disease onset. The proposed model of immune complexes driving disease initial disease etiology by Fc receptor activation of immune cells and platelets, resulting in elevated histamine and serotonin levels, is testable and is consistent with disease symptoms and current treatments.

Effect of ligand structure and metal center on ethylene oligomerization with N, N′ Schiff base late transition complexes: experiments and calculations

A series of N, N’ bis(pyridine-imine) Schiff base late transition metal (Fe, Co, and Ni) complexes with different ligand structures and catalytic active sites were synthesized. Ethylene oligomerization results showed that bis(pyridine-imine) iron complex had the highest catalytic activity (10.8 × 105 g/mol Fe h), and the catalytic activity of cobalt complex was the lowest (2.5 × 105 g/mol Co h); nickel complex had the highest selectivity toward high carbon olefins (28.6%), while the iron complex had the lowest (0.2%). The structure-activity relationship between the catalyst structure and catalytic properties for ethylene oligomerization was further studied by density functional theory (DFT) calculations. The bis(pyridine-imine) iron complex had the highest energy gap value and the most stable catalyst structure, which was more conducive to oligomerization; and the N–M–N bond of the nickel complex had the smallest bond angle, which was beneficial for chain growth. Based on the Cossee mechanism, a mechanism for ethylene oligomerization catalyzed by bis(pyridine-imine) metal complexes was proposed. To further study the micro reaction process of ethylene oligomerization, a molecular model of pyridine imine nickel complex and its catalytic ethylene oligomerization reaction path were proposed. The structure and energy of the reaction intermediate and transition state were calculated using DFT. The molecular model of the nickel complex had a lower ethylene insertion barrier and β-H elimination of energy barriers, indicating that the molecular model of the pyridine imine nickel complex had ethylene oligomerization active centers.

The GōMartini Approach: Revisiting the Concept of Contact Maps and the Modelling of Protein Complexes

The GōMartini Approach: Revisiting the Concept of Contact Maps and the Modelling of Protein Complexes

Contributions of the Abductor Muscles to Rotational and Distractive Stability of the Hip in a Biomechanical Cadaveric Model.

The gluteus minimus (GMin) and gluteus medius (GMed) are important dynamic stabilizers of the hip, but quantitative data on their biomechanical roles in stabilizing the hip are currently lacking. To (1) establish a reproducible biomechanical cadaveric model of the hip abductor complex and (2) characterize the effects of loading the GMin and GMed on extraneous femoral rotation and distraction. Controlled laboratory study. A total of 10 hemipelvises were tested in 4 muscle loading states: (1) unloaded, (2) the GMin loaded, (3) the GMed loaded, and (4) both the GMin and GMed loaded. Muscle loads were applied via cables, pulleys, and weights attached to the tendons to replicate the anatomic lines of action. Specimens were tested under internal rotation; external rotation; and axial traction forces at 0°, 15°, 30°, 60°, and 90° of hip flexion. When loaded together, the GMin and GMed reduced internal rotation motion at all hip flexion angles (P < .05) except 60° and reduced external rotation motion at all hip flexion angles (P < .05) except 0°. Likewise, when both the GMin and GMed were loaded, femoral distraction was decreased at all angles of hip flexion (P < .05). The results of this study demonstrated that the GMin and GMed provide stability against rotational torques and distractive forces and that the amount of contribution depends on the degree of hip flexion. Improved understanding of the roles of the GMin and GMed in preventing rotational and distractive instability of the hip will better guide treatment of hip pathologies and optimize nonoperative and operative therapies.

Numerical investigation of heat transfer enhancement in dielectric fluids through electro-thermo-capillary convection

In this study, a 2D numerical analysis was conducted to investigate electro-thermo-capillary convection in a 2D enclosure filled with a dielectric fluid. The enclosure had a free top surface and was subjected to buoyancy and electrical forces. The study considered a strong unipolar injection of electric charge (C = 10), a mobility number (M = 10), and a Prandtl number (Pr = 10). Calculations were performed for various thermal Rayleigh numbers (Ra) ranging from 5000 to 50,000, Marangoni numbers (Ma) varying from −5000 to 5000 and electric Rayleigh numbers (T) ranging from 100 to 800. The coupled equations governing the electro-thermo-convection problem (Navier-Stokes, energy, charge density transport, and the Maxwell-Gauss equations) were established and solved numerically using the FVM. This study involved mathematical modelling of complex and coupled phenomena, considering viscous, thermal, thermocapillary, and electrical instabilities. The findings showed a significant improvement in heat transfer with higher electrical and thermal Rayleigh numbers. Furthermore, the control of different forces led to an increase in the Nusselt number. Specifically, the application of thermal forces resulted in a 70% increase, while the use of thermocapillary forces led to a remarkable 169% increase. Additionally, electrical forces resulted in an impressive 224% increase. Multi-parameter correlations were established to estimate the Nusselt number as a function of the Marangoni, thermal and electrical Rayleigh numbers.

AutoRNC: An automated modeling program for building atomic models of ribosome-nascent chain complexes

The interpretation of experimental studies of co-translational protein folding often benefits from the use of computational methods that seek to model or simulate the nascent chain and its interactions with the ribosome. Building realistic 3D models of ribosome-nascent chain (RNC) constructs often requires expert knowledge, so to circumvent this issue, we describe here AutoRNC, an automated modeling program capable of constructing large numbers of plausible atomic models of RNCs within minutes. AutoRNC takes input from the user specifying any regions of the nascent chain that contain secondary or tertiary structure and attempts to build conformations compatible with those specifications-and with the constraints imposed by the ribosome-by sampling and progressively piecing together dipeptide conformations extracted from the Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB). Despite using only modest computational resources, we show here that AutoRNC can build plausible conformations for a wide range of RNC constructs for which experimental data have already been reported.

Contractile and Genetic Characterization of Cardiac Constructs Engineered from Human Induced Pluripotent Stem Cells: Modeling of Tuberous Sclerosis Complex and the Effects of Rapamycin.

The implementation of three-dimensional tissue engineering concurrently with stem cell technology holds great promise for in vitro research in pharmacology and toxicology and modeling cardiac diseases, particularly for rare genetic and pediatric diseases for which animal models, immortal cell lines, and biopsy samples are unavailable. It also allows for a rapid assessment of phenotype-genotype relationships and tissue response to pharmacological manipulation. Mutations in the TSC1 and TSC2 genes lead to dysfunctional mTOR signaling and cause tuberous sclerosis complex (TSC), a genetic disorder that affects multiple organ systems, principally the brain, heart, skin, and kidneys. Here we differentiated healthy (CC3) and tuberous sclerosis (TSP8-15) human induced pluripotent stem cells (hiPSCs) into cardiomyocytes to create engineered cardiac tissue constructs (ECTCs). We investigated and compared their mechano-elastic properties and gene expression and assessed the effects of rapamycin, a potent inhibitor of the mechanistic target of rapamycin (mTOR). The TSP8-15 ECTCs had increased chronotropy compared to healthy ECTCs. Rapamycin induced positive inotropic and chronotropic effects (i.e., increased contractility and beating frequency, respectively) in the CC3 ECTCs but did not cause significant changes in the TSP8-15 ECTCs. A differential gene expression analysis revealed 926 up- and 439 down-regulated genes in the TSP8-15 ECTCs compared to their healthy counterparts. The application of rapamycin initiated the differential expression of 101 and 31 genes in the CC3 and TSP8-15 ECTCs, respectively. A gene ontology analysis showed that in the CC3 ECTCs, the positive inotropic and chronotropic effects of rapamycin correlated with positively regulated biological processes, which were primarily related to the metabolism of lipids and fatty and amino acids, and with negatively regulated processes, which were predominantly associated with cell proliferation and muscle and tissue development. In conclusion, this study describes for the first time an in vitro TSC cardiac tissue model, illustrates the response of normal and TSC ECTCs to rapamycin, and provides new insights into the mechanisms of TSC.

Spin-Orbit Effects on Exciton Complexes in Diamond.

Ultrafine splittings are found in the optical absorption spectra of boron-doped diamond measured with high resolution. An analytical model of an exciton complex is developed, which permits assigning all absorption lines and sizing the interactions among the constituent charges and crystal field. We conclude that the entry of split-off holes in the acceptor-bound exciton fine structure yields two triplets separated by a spin-orbit splitting of 14.3meV. Our findings thereby resolve a long-standing controversy [R. Sauer et al., Revised fine splitting of excitons in diamond, Phys. Rev. Lett. 84, 4172 (2000).PRLTAO0031-900710.1103/PhysRevLett.84.4172; M. Cardona et al., Comment on "Revised fine splitting of excitons in diamond,", Phys. Rev. Lett. 86, 3923 (2001).PRLTAO0031-900710.1103/PhysRevLett.86.3923; R. Sauer and K. Thonke, Sauer and Thonke reply, Phys. Rev. Lett. 86, 3924 (2001).PRLTAO0031-900710.1103/PhysRevLett.86.3924], revealing the underlying physics common in diverse semiconductors, including diamond.

Long-read sequencing reveals the structural complexity of genomic integration of HPV DNA in cervical cancer cell lines

BackgroundCervical cancer (CC) causes more than 311,000 deaths annually worldwide. The integration of human papillomavirus (HPV) is a crucial genetic event that contributes to cervical carcinogenesis. Despite HPV DNA integration is known to disrupt the genomic architecture of both the host and viral genomes in CC, the complexity of this process remains largely unexplored.ResultsIn this study, we conducted whole-genome sequencing (WGS) at 55-65X coverage utilizing the PacBio long-read sequencing platform in SiHa and HeLa cells, followed by comprehensive analyses of the sequence data to elucidate the complexity of HPV integration. Firstly, our results demonstrated that PacBio long-read sequencing effectively identifies HPV integration breakpoints with comparable accuracy to targeted-capture Next-generation sequencing (NGS) methods. Secondly, we constructed detailed models of complex integrated genome structures that included both the HPV genome and nearby regions of the human genome by utilizing PacBio long-read WGS. Thirdly, our sequencing results revealed the occurrence of a wide variety of genome-wide structural variations (SVs) in SiHa and HeLa cells. Additionally, our analysis further revealed a potential correlation between changes in gene expression levels and SVs on chromosome 13 in the genome of SiHa cells.ConclusionsUsing PacBio long-read sequencing, we have successfully constructed complex models illustrating HPV integrated genome structures in SiHa and HeLa cells. This accomplishment serves as a compelling demonstration of the valuable capabilities of long-read sequencing in detecting and characterizing HPV genomic integration structures within human cells. Furthermore, these findings offer critical insights into the complex process of HPV16 and HPV18 integration and their potential contribution to the development of cervical cancer.