Biology subjects

Pan, X.

Publications and source records attributed to Pan, X..

At least 127 records · Page 7Linked to original sources

bioRxiv2022

Heterologous boost with mRNA vaccines against SARS-CoV-2 Delta/Omicron variants following an inactivated whole-virus vaccine

The coronavirus SARS-CoV-2 has mutated quickly and caused significant global damage. This study characterizes two mRNA vaccines ZSVG-02 (Delta) and ZSVG-02-O (Omicron BA.1), and associating heterologous prime-boost strategy following the prime of a most widely administrated inactivated whole-virus vaccine (BBIBP-CorV). The ZSVG-02-O induces neutralizing antibodies that effectively cross-react with Omicron subvariants following an order of BA.1>BA.2>BA.4/5. In naive animals, ZSVG-02 or ZSVG-02-O induce humoral responses skewed to the vaccines targeting strains, but cellular immune responses cross-react to all variants of concern (VOCs) tested. Following heterologous prime-boost regimes, animals present comparable neutralizing antibody levels and superior protection across all VOCs. Single-boost only generated ancestral and omicron dual-responsive antibodies, probably by "recall" and "reshape" the prime immunity. New Omicron-specific antibody populations, however, appeared only following the second boost with ZSVG-02-O. Overall, our results support a heterologous boost with ZSVG-02-O, providing the best protection against current VOCs in inactivated virus vaccine- primed populations.

molecular biology↗

bioRxiv2022

Leveraging Scaffold Information to Predict Protein-ligand Binding Affinity with an Empirical Graph Neural Network

MotivationProtein-ligand binding affinity prediction is an important task in structural bioinformatics for drug discovery and design. Although various scoring functions have been proposed, it remains challenging to accurately evaluate the binding affinity of a protein-ligand complex with known bound structure due to the potential preference of scoring system. In recent years, deep learning techniques have been applied to scoring functions without sophisticated feature engineering. Nevertheless, existing methods cannot model the differential contribution of atoms in various regions of proteins, and the relationship between atom properties and intermolecular distance is also not fully explored. ResultsWe propose a novel empirical graph neural network for accurate protein-ligand binding affinity prediction (EGNA). Graphs of protein, ligand and their interactions are constructed based on different regions of each bound complex. Proteins and ligands are effectively represented by graph convolutional layers, enabling the EGNA to capture interaction patterns precisely by simulating empirical scoring functions. The contributions of different factors on binding affinity can thus be transparently investigated. EGNA is compared with the state-of-the-art machine learning-based scoring functions on two widely used benchmark datasets. The results demonstrate the superiority of EGNA and its good generalization capability. Availability and implementationThe web server and source code of EGNA is available at www.csbio.sjtu.edu.cn/bioinf/EGNA and https://github.com/chunqiux/EGNA. Contacthbshen@sjtu.edu.cn or 2008xypan@sjtu.edu.cn Supplementary informationSupplementary data are available at Bioinformatics online.

bioinformatics↗

bioRxiv2022

Fibrillarin-1 and Fibrillarin-2 are required for divergent cell lineage development in planarian homeostasis and regeneration

Ribosome heterogeneity has been revealed to exist in different cell types during development. However, the function and regulatory mechanisms of ribosome heterogeneity in missing tissue regeneration have yet to be reported. We used the planarian Schmidtea mediterranea with whole-body regenerative capability as a model and revealed the function of the rRNA modification protein fibrillarin in cell lineage development and tissue regeneration. We identified two fibrillarin homologs in planarian, Smed-fbl-1 (fbl-1) and Smed-fbl-2 (fbl-2), with distinct expression patterns. While fbl-2 regulates stem cell proliferation and multiple progenitor cell differentiation, fbl-1 participates in epidermal lineage late-stage specification and wound response. This study indicates that fibrillarin, a nucleolar protein, can respond to wounds and function in distinct cell types, suggesting the existence and critical roles of ribosome heterogeneity in stem cells and tissue regeneration.

developmental biology↗

bioRxiv2022

Cell-type-specific aberrant R-loop accumulation regulates target gene and confers cell-specificity

Aberrant R-loops have been found associated with diverse biological dysfunction, including cancers and neurological disorders. However, there isnt any systematic research to characterize aberrant R-loops at the whole genome level at a large scale. Here, we identified aberrant R-loops, including proliferative and suppressive R-loops of 5 end, body, 3 end respectively for the first time, which are found prevalent and vary across diverse physiological conditions. After that, we proposed a deep neural network-based framework, named Deep R-looper Discriminant to identify aberrant R-loops against housekeeping R-loops. To evaluate the predictive performance of the deep learning framework, we constructed multiple prediction models as benchmarks and it showed our framework achieves robust performance for identifying aberrant R-loops against those normal R-loops. Furthermore, we found the customized Deep R-looper Discriminant was capable of distinguishing between proliferative and suppressive R-loops at 5 end, body, 3 end respectively, outperforming baselines. When inspecting the contribution of epigenetic marks to aberrant R-loops of each class, we inferred landmark epigenetic modifications which play a crucial role in the differentiated formation of those aberrant R-loops, and cell line specificity of epigenetic marks map was found as well. To explore the characteristics of these aberrant R-loops, we depicted the histone landscapes for aberrant R-loops. Finally, we integrated omics and identified target genes regulated directly by aberrant R-loops and found key transcription factors involved in R-loop regulation, which may be implicated in conferring cell-specificity and cancer development and progression.

bioinformatics↗

bioRxiv2022

OUGene 2.0: An updated disease-associated over- and under-expressed gene database by mining full-text articles

Many diseases are closely associated with over- or under-expressed genes. In order to cover more up to date associations between over- or under-expressed genes and various diseases, we develop an updated database OUGENE 2.0 for disease-associated over- and under-expressed genes by automatic full-text mining. In total, the new OUGene 2.0 includes 197,236 associations between 12,672 diseases and 11,542 over- or under-expressed genes, which increases by about 5 folds compared to the previous version of OUGene. A novel method for rescaling the raw score based on support evidences is designed to prioritize the mined associations. OUGene 2.0 provides a holistic view of disease-gene associations and it supports user-friendly data exploration at www.csbio.sjtu.edu.cn/bioinf/OUGene for academic use.

bioinformatics↗

bioRxiv2022

Skeletal muscle lineage is dispensable for appendage regeneration in axolotl

Regeneration of a complex appendage structure such as limb requires hierarchical coordination of multiple types of tissues. Muscles, as one of the major cell masses in limbs, have been reported recently to be critical to guide other tissue regeneration in planaria, but its function and relationship to other cells in vertebrate complex regeneration have been unclear. Here, we use Pax7 mutant axolotls, in which the limb muscle is developmentally lost, to investigate limb regeneration in the absence of skeletal muscle. We find that the pattern of regenerated limbs is normal in Pax7 mutants compared to the controls. Lack of muscles do not affect the proliferation of fibroblasts, another major population in limbs. Furthermore, using single cell RNA-sequencing, we demonstrate that the cell type composition in completely regenerated limbs in Pax7 mutants is similar to that in the controls, except the lack of cell types in muscle lineage. Our study reveals skeletal muscle is not required for the guidance of complex tissue regeneration in axolotls, and provides new views of the tissue hierarchy in vertebrate appendage regeneration.

cell biology↗

bioRxiv2022

Downregulating PTBP1 fails to convert astrocytes into hippocampal neurons and to alleviate symptoms in Alzheimer's mouse models

Conversion of astroglia into functional neurons has been considered as a promising therapeutic strategy for neurodegenerative diseases. Recent studies reported that downregulation of the RNA binding protein, PTBP1, converts astrocytes into neurons in situ in multiple mouse brain regions, consequently improving pathological phenotypes associated with Parkinsons disease, RGC loss, and aging. Here, we demonstrate that PTBP1 downregulation using antisense oligonucleotides or an astrocyte specific AAV-mediated shRNA system fails to convert hippocampal astrocytes into neurons in WT, and {beta}-amyloid (5xFAD) and tau (PS19) Alzheimers disease (AD) mouse models, and fails to reverse synaptic/cognitive deficits and AD-associated pathology. Similarly, PTBP1 downregulation cannot convert astrocytes into neurons in the striatum and substantia nigra. Together, our study suggests that cell fate conversion strategy for neurodegenerative disease therapy through manipulating one single gene, such as PTBP1, warrants more rigorous scrutiny.

neuroscience↗

bioRxiv2022

Changes of urinary proteomic before and after QIV and COVID-19 vaccination

We first collected a young peoples urine samples cohort of quadrivalent influenza vaccine. Urine protein at 24 hours after vaccination was enriched in immune-related pathways, though the specific pathways varied. Perhaps because different people may be in a previous life encountered some of the viruses in the vaccine, the second immunization was triggered. Or everyone has a different constitution, exposure to the same virus triggering different immunity. We then collected urine samples from several uninfected SARS-CoV-2 young people before and after the first, second, and third doses of the COVID-19 vaccine. We found that the differential protein compared between after the second dose (24h) and before the second dose enriched pathways were involved in regulated exocytosis and immune-related pathways, indicating not first exposure to antigen. Surprisingly, the urine differential protein-enriched pathways before and after the first dose were similar to those before and after the second dose. We assume that although the volunteers have not been infected with SARS-CoV-2, they might have been exposed to other coimmunogenic coronaviruses. 2~4h after the third vaccination, the differentially expressed protein also enriched regulated exocytosis and immune-related pathways, indicating that the body has triggered the immune response in a very short time after vaccination, and urine proteome is a good window to monitor the changes of human immune function.

biochemistry↗

bioRxiv2022

Eight week dietary inclusion of nitrite-containing frankfurter exacerbates colorectal cancer pathology, increases oxidative stress, alters metabolism and causes gut dybiosis in APCmin mice

Colorectal cancer (CRC) is the second most prevelant malignancy in Europe and diet is an important modifiable risk factor. Processed meat consumption, including meats with preservative salts such as sodium nitrite, have been implicated in CRC pathogenesis. This study investigated how the CRC pathology and metabolic status of adenomatous polyposis coli (APC) multiple intestinal neoplasia (min) mice was perturbed following 8 weeks of pork meat consumption. Dietary inclusions (15%) of either nitrite-free pork, nitrite-free sausage or nitrite-containing sausage (frankfurter) were compared against a parallel control group (100% chow). Comprehensive studies investigated: gastrointestinal tract histology (tumours, aberrant crypt foci (ACF) and mucin deplin foci (MDF), lipid peroxidation (urine and serum), faecal microbiota and serum metabolomics (599 metabolites). After 8 weeks mice consuming the frankfurter diet had 53% more (P=0.014) gastrointestinal tumours than control, although ACF and MDF did not differ. Urine and serum lipid peroxidation markers were 59% (P=0.001) and 108% (P=0.001) higher, respectively in the frankfurter group. Gut dysbiosis was evident in these mice with comparably fewer Bacteriodes and more Firmicutes. Fasting serum levels of trimethylamine N-oxide (TMAO) and numerous triglycerides were elevated. Various serum phosphotidylcholine species were decreased. These results demonstrate that nitrite-containing sausages may exaccerbate the development of CRC pathology in APCMin mice to a greater extent than nitrite-free sausages, and this is associated with greater lipid peroxidation, wide-ranging metabolic alternation and gut dysbiosis.

biochemistry↗

bioRxiv2022

Why SARS-CoV-2 Omicron variant is milder? A single high-frequency mutation of structural envelope protein matters.

SARS-CoV-2 Omicron variant is highly transmissible and extensive morbidity, which has raised concerns for antiviral therapy. In addition, the molecular basis for the attenuated pathogenicity and replication capacity of Omicron remains elusive. Here, we report for the first time that a high-frequency mutation T9I on 2-E of SARS-CoV-2 variant Omicron forms a non-selective ion channel with abolished calcium permeability and reduced acid sensitivity compared to the WT channel. In addition, T9I caused less cell death and a weaker cytokine production. The channel property changes might be responsible for the Omicron variant releases less efficiently and induces a comparatively lower level of cell damage in the infected cells. Our study gives valuable insights into key features of the Omicron variant, further supporting 2-E is a promising drug target against SARS-CoV-2 and providing critical information for the COVID-19 treatment.

microbiology↗

bioRxiv2022

Single-cell atlas of epithelial and stromal cell heterogeneity by lobe and strain in the mouse prostate

Evaluating the complex interplay of cell types in the tissue microenvironment is critical to understanding the origin and progression of diseases in the prostate and potential opportunities for intervention. Mouse models are an essential tool to investigate the molecular and cell-type-specific contributions of prostate disease at an organismal level. While there are well-documented differences in the extent, timing, and nature of disease development in various genetically engineered mouse models in different mouse strains and prostate lobes within each mouse strain, yet, the underlying molecular phenotypic differences in cell types across mouse strains and prostate lobes are incompletely understood. To address this, we examined the single-cell transcriptomes of individual mouse prostate lobes from two commonly used mouse strains, FVB/NJ and C57BL/6J. Data dimensionality reduction and clustering analysis revealed that basal and luminal cells possessed strain-specific transcriptomic differences, with luminal cells also displaying marked lobe-specific differences. Additionally, three rare populations of epithelial cells clustered independently of strain and lobe: one population of luminal cells expressing Foxi1 and components of the vacuolar ATPase proton pump (Atp6v0d2 and Atp6v1g3), another population expressing Psca and other stem cell-associated genes (Ly6a/Sca-1, Tacstd2/Trop-2), and a neuroendocrine population expressing Chga, Chgb, and Syp. In contrast, stromal cell clusters, including fibroblasts, smooth muscle cells, endothelial cells, pericytes, and immune cell types, were conserved across strain and lobe, clustering largely by cell type and not by strain or lobe. One notable exception to this was the identification of two distinct fibroblast populations that we term subglandular fibroblasts and interstitial fibroblasts based on their strikingly distinct spatial distribution in the mouse prostate. Altogether, these data provide a practical reference of the transcriptional profiles of mouse prostate from two commonly used mouse strains and across all four prostate lobes.

cell biology↗

bioRxiv2022

Deep learning based on multi-omics integration identifies potential therapeutic targets in breast cancer

Effective and precise classification of breast cancer patients for their disease risks is critical to improve early diagnosis and patient survival. In the recent past, a significant amount of multi-omics data derived from cancer patients has emerged. However, a robust framework for integrating multi-omics data to subgroup cancer patients and predict survival prognosis is still lacking. In addition, effective therapeutic targets for treating breast cancer patients with poor prognoses are in dire need. To begin to resolve this difficulty, we developed and optimized a sophisticated deep learning-based model in breast cancer that can accurately stratify patients based on their prognosis. We built a survival-associated predictive framework integrating transcription profile, miRNA expression, somatic mutations, copy number variation, DNA methylation and protein expression. This framework achieved promising performance in distinguishing high-risk breast cancer patients from those with good prognoses. Furthermore, we constructed multiple fully connected neural networks that are trained on prioritized multi-omics signatures or even only potential single-omics signatures, based on our customized scoring system. Together, the landmark multi-omics signatures we identified may serve as potential therapeutic targets in breast cancer.

bioinformatics↗

bioRxiv2022

Interactive effect matters: a combination of herbivory degree and the ratio of generalist to specialist better predicts evolution of plant defense

Herbivory degree and the ratio of generalist to specialist herbivores have long been treated as two important but independent factors in shaping the evolution of plant defense. However, this assumption of independency is poorly supported and has resulted in great controversy in explaining the patterns of plant defense. Here we investigated the possible interaction between herbivory degree and generalist-to-specialist ratio using a cost-benefit model of defense evolution in plants. Our results showed that, with increasing generalist herbivore proportion, plant defense investment increases when herbivory degree is low and decreases when herbivory degree is high. These results provide the first theoretical support for the interactive effect of herbivory degree and ratio of generalist/specialist affecting plant defense, which integrate many of the previous results (e.g. latitudinal patterns of plant defense and defense evolution of invasive plants) and put them into a more general theoretical context.

evolutionary biology↗

bioRxiv2022

Genomic insights into the phylogeny and biomass-degrading enzymes of rumen ciliates

Understanding the biodiversity and genetics of the gut microbiome has important implications for host physiology. One underexplored and elusive group is ciliated protozoa, which play crucial roles in regulating gut microbial interactions. Integrating single-cell sequencing and an assembly-and-identification pipeline, we acquired 52 high-quality ciliate genomes of 22 rumen morphospecies for all major abundant clades. With these genomes, we firstly resolved the taxonomic and phylogenetic framework that reclassified them into 19 species spanning 13 genera and reassigned the genus Dasytricha from Isotrichidae to a new family Dasytrichidae. Via extensive horizontal gene transfer and gene family expansion, rumen ciliates possess a broad array of enzymes to synergistically degrade plant and microbial carbohydrates. In particular, [~]80% of the degrading enzymes in Diplodiniinae and Ophryoscolecinae act on plant cell wall, and the high activities of their cellulase, xylanase and lysozyme reflect the potential of ciliate enzymes for biomass-conversion. Additionally, the new ciliate dataset greatly facilitated the rumen metagenomic analyses by allowing [~]12% of reads to be classified.

microbiology↗

bioRxiv2021

Molecular probes of spike ectodomain and its subdomains for SARS-CoV-2 variants, Alpha through Omicron

Since the outbreak of the COVID-19 pandemic, widespread infections have allowed SARS-CoV-2 to evolve in human, leading to the emergence of multiple circulating variants. Some of these variants show increased resistance to vaccines, convalescent plasma, or monoclonal antibodies. In particular, mutations in the SARS-CoV-2 spike have drawn attention. To facilitate the isolation of neutralizing antibodies and the monitoring the vaccine effectiveness against these variants, we designed and produced biotin-labeled molecular probes of variant SARS-CoV-2 spikes and their subdomains, using a structure-based construct design that incorporated an N-terminal purification tag, a specific amino acid sequence for protease cleavage, the variant spike-based region of interest, and a C-terminal sequence targeted by biotin ligase. These probes could be produced by a single step using in-process biotinylation and purification. We characterized the physical properties and antigenicity of these probes, comprising the N-terminal domain (NTD), the receptor-binding domain (RBD), the RBD and subdomain 1 (RBD-SD1), and the prefusion-stabilized spike ectodomain (S2P) with sequences from SARS-CoV-2 variants of concern or of interest, including variants Alpha, Beta, Gamma, Epsilon, Iota, Kappa, Delta, Lambda, Mu, and Omicron. We functionally validated probes by using yeast expressing a panel of nine SARS-CoV-2 spike-binding antibodies and confirmed sorting capabilities of variant probes using yeast displaying libraries of plasma antibodies from COVID-19 convalescent donors. We deposited these constructs to Addgene to enable their dissemination. Overall, this study describes a matrix of SARS-CoV-2 variant molecular probes that allow for assessment of immune responses, identification of serum antibody specificity, and isolation and characterization of neutralizing antibodies.

immunology↗

bioRxiv2021

Supramolecular assembly of chloroplast NAD(P)H dehydrogenase-like complex with photosystem I from Arabidopsis thaliana

Cyclic electron transport/flow (CET/CEF) in chloroplasts is a regulatory mechanism crucial for optimization of plant photosynthetic efficiency. CET is catalyzed by a membrane-embedded NAD(P)H dehydrogenase-like (NDH) complex containing at least 29 protein subunits and associating with photosystem I (PSI) to form the NDH-PSI supercomplex. Here we report the 3.9 [A] resolution structure of Arabidopsis thaliana NDH-PSI (AtNDH-PSI) supercomplex. We have constructed structural models for 26 AtNDH subunits, among which 11 subunits are unique to chloroplast and stabilize the core part of NDH complex. In the supercomplex, one NDH can bind up to two PSI-LHCI complexes at both sides of its membrane arm. Two minor LHCIs, Lhca5 and Lhca6, each present in one PSI-LHCI, interact with NDH and contribute to the supercomplex formation and stabilization. Our results showed structural details of the supercomplex assembly and provide molecular basis for further investigation of the regulatory mechanism of CEF in plants.

plant biology↗

bioRxiv2021

METTL3 facilitates hepatic fibrosis progression via m6A-YTHDF2 dependent silencing of GPR161

Hepatic fibrosis (HF) is a very common condition seen in millions of patients with various liver diseases. N6-methyladenosine (m6A) plays critical roles in various biological and pathological processes. However, the role of m6A and its main methyltransferase METTL3 in HF remains obscure. Here, we reported that METTL3 expression was elevated in HSCs from CCl4 induced fibrotic liver. METTL3 knockdown in HSCs mediated by recombinant adeno-associated-virus serotype 9 packed short hairpin RNA against METTL3 alleviated liver injury and fibrosis compared to empty carrier group. Mechanistically, the decreased liver fibrosis in CCl4-treated HSC-specific METTL3 knockdown mice was due to the increased GPR161 that is a suppressor of Hedgehog pathway, a well-known pathway to activate in liver injury and regeneration. As expect, GPR161 transferred into HSCs alleviated liver fibrosis and HSC activation. Forced GPR161 expression inhibited Gli3 activated form nuclear accumulation and subsequently suppressed fibrosis-associate gene expression. Conclusion, HSC-specific deletion of METTL3 inhibits liver fibrosis via elevated GPR161 expression, which subsequently suppressed Hedgehog pathway activation and fibrosis-associated genes expression, providing novel therapeutic targets for HF therapy. Synopsis O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=196 SRC="FIGDIR/small/472749v1_ufig1.gif" ALT="Figure 1"> View larger version (78K): org.highwire.dtl.DTLVardef@1245f3aorg.highwire.dtl.DTLVardef@e7effdorg.highwire.dtl.DTLVardef@13ce319org.highwire.dtl.DTLVardef@61be8b_HPS_FORMAT_FIGEXP M_FIG C_FIG The role of RNA m6A methyltransferase METTL3 in the progression of hepatic fibrosis is unclear. Here, we reveal that suppresses m6A modification by depletion of METTL3 in Hepatic Stellate Cells (HSCs), stabilizes the GPR161 transcripts, that involved in suppressing Hedgehog signaling pathway, through YTHDF2, thereby alleviating the fibrosis feature of CCl4-induced liver injury. O_LIDisruption of m6A methyltransferases METTL3 in HSCs alleviates liver fibrosis feature. C_LIO_LIMETTL3 depletion in liver HSCs suppresses its activation by suppressing Hedgehog signaling pathway through stabilizing GPR161 transcripts in an m6A-YTHDF2 dependent manner. C_LIO_LIGPR161 activates PKA that mediates phosphorylation and degradation of full-length Gli3 (Gli3-FL) protein, then the short Gli3 (Gli3-R) translocated into the nucleus and suppresses the fibrosis associated gene transcription. C_LIO_LIThe elevated METTL3 expression is attribute to its promoter H3K27ac modification. C_LI

molecular biology↗

bioRxiv2021

Cell free extrachromosomal circular DNA is common in human urine

Cell free extrachromosomal circular DNA (eccDNA) is evolving as a potential biomarker in liquid biopsies for disease diagnosis. In this study, an optimized next generation sequencing-based Circle-Seq method was developed to investigate urinary cell free eccDNA (ucf-eccDNA) from 28 adult healthy volunteers (mean age = 28, 19 males/ 9 females). The genomic distributions and sequence compositions of ucf-eccDNAs were comprehensively characterized. Approximately 1.2 million unique ucf-eccDNAs are identified, covering 14.9% of the human genome. Comprehensive characterization of ucf-eccDNAs show that ucf-eccDNAs contain higher GC content than flanking genomic regions. Most eccDNAs are less than 1000 bp and present four pronounced peaks at 203, 361, 550 and 728 bp, indicating the association between eccDNAs and the numbers of intact nucleosomes. Analysis of genomic distribution of ucf-eccDNAs show that eccDNAs are found in all chromosomes but enriched in chromosomes i.e. chr.17, 19 and 20 with high density of protein-codding genes, CpG islands, SINE and simple repeat elements. Lastly, analysis of sequence motif signatures at eccDNA junction sites reveal that direct repeats (DRs) are commonly found, indicating a potential role of DRs in eccDNA biogenesis. This work underscores the deep sequencing analysis of ucf-eccDNAs and provides a valuable reference resource for exploring potential applications of ucf-eccDNA as diagnostic biomarkers of urogenital disorders in the future. Significance StatementExtrachromosomal circular DNA (eccDNA) is an important genetic element and a biomarker for disease diagnosis and treatment. In this study, we conduct a comprehensive characterization of urinary cell free eccDNA (ucf-eccDNA) in 28 heathy subjects. Over one million ucf-eccDNAs are identified. Ucf-eccDNAs are characterized as high GC content. The size of most ucf-eccDNAs is less than 1000 bp and enriched in four peaks resembling the size of single, double, triple, and quadruple nucleosomes. The genomic distribution of ucf-eccDNAs is enriched in generic regions, protein-coding genes, Alu, CpG islands, SINE and simple repeats. Sequence motif analysis of ucf-eccDNA junctions identified simple direct repeats (DRs) commonly presented in most eccDNAs, suggesting potential roles of DRs in eccDNA biogenesis.

genomics↗