Biology subjects

Ni, Z.

Publications and source records attributed to Ni, Z..

At least 19 recordsLinked to original sources

bioRxiv2026

Orbitrap Collision Cross Section Measurements Enhance Isomer Annotations in Lipidomics

Despite advances in high-resolution mass spectrometry (HRMS), confident lipid annotation remains challenging due to the extensive chemical diversity of the lipidome and the prevalence of isomeric species. Ion mobility collision cross section (CCS) measurements provide structural information that complements HRMS; however, not all HRMS platforms can perform these measurements, necessitating a trade-off among mass resolution, accuracy, and robustness. Here, we introduce a method to infer lipid CCS values directly from liquid chromatography (LC)-Orbitrap MS experiments (OrbiCCS). We show that Orbitrap mass analyzer pressure readings, and therefore CCS values, are influenced by the LC gradient solvent composition, requiring correction using isotopically labeled internal standards injected post-column. We also show that hundreds of lipid features can be assigned OrbiCCS values in a single LC run, with average precision better than 1% and an accuracy of 1-2% relative to reference DTCCS and TIMSCCS values. This excellent CCS accuracy not only enables more reliable annotation of lipid species in complex mixtures by matching OrbiCCS values to reference databases but also accelerates lipid structural elucidation based on the unknowns position in OrbiCCS-retention time-m/z space.

biochemistry↗

bioRxiv2026

Rigidity-Aware Geometric Pretraining for Protein Design and Conformational Ensembles

AO_SCPLOWBSTRACTC_SCPLOWGenerative models have recently advanced de novo protein design by learning the statistical regularities of natural structures. However, current approaches face three key limitations: (1) Existing methods cannot jointly learn protein geometry and design tasks, where pretraining can be a solution; (2) Current pretraining methods mostly rely on local, non-rigid atomic representations for property prediction downstream tasks, limiting global geometric understanding for protein generation tasks; and (3) Existing approaches have yet to effectively model the rich dynamic and conformational information of protein structures. To overcome these issues, we introduce RigidSSL (Rigidity-Aware Self-Supervised Learning), a geometric pretraining framework that front-loads geometry learning prior to generative finetuning. Phase I (RigidSSL-Perturb) learns geometric priors from 432K structures from the AlphaFold Protein Structure Database with simulated perturbations. Phase II (RigidSSL-MD) refines these representations on 1.3K molecular dynamics trajectories to capture physically realistic transitions. Underpinning both phases is a bi-directional, rigidity-aware flow matching objective that jointly optimizes translational and rotational dynamics to maximize mutual information between conformations. Empirically, RigidSSL variants improve designability by up to 43% while enhancing novelty and diversity in unconditional generation. Furthermore, RigidSSL-Perturb improves the success rate by 5.8% in zero-shot motif scaffolding and RigidSSL-MD captures more biophysically realistic conformational ensembles in G protein-coupled receptor modeling. The code is available on this repository.

bioinformatics↗

bioRxiv2025

NIPBL-mediated 3D genome folding translates enhancer priming into gene activation and safeguards lineage fidelity during embryonic transitions

Precise gene control by complex regulatory landscapes is fundamental to embryo development, yet the instructive role of 3D genome architecture remains controversial. While acute cohesin depletion completely disrupts genome folding, it yields modest transcriptional impacts, but these findings are often confounded by cohesins essential roles in cell division and proliferation. Here, we resolve this discrepancy by decoupling architectural functions from cell-cycle roles using an acute NIPBL degron system. By integrating single-gene imaging with single-cell and bulk multi-omics during mouse pluripotency transitions and germ-layer specification, we show that NIPBL-mediated cohesin function is required for proper de novo activation of lineage-specifying genes. Mechanistically, NIPBL translates epigenetic priming into transcriptional outputs by physically bringing distal enhancers and target promoters into proximity. We further uncover a dual regulatory role: an acute requirement for establishing new enhancer-promoter interactions during cell state transitions and a long-term role in safeguarding transcriptional fidelity by preventing ectopic gene de-repression. Our findings demonstrate that NIPBL/cohesin-orchestrated genome folding facilitates the faithful execution of developmental gene expression programs. HighlightsO_LIAcute NIPBL depletion decouples the architectural functions of cohesin from its essential roles in chromosome segregation and cell cycle progression. C_LIO_LINIPBL-mediated loop extrusion is required to translate the epigenetic priming of distal enhancers into de novo gene activation during embryonic state transitions. C_LIO_LINIPBL is a "rate-limiting physical relay" required to bring distal enhancers and target promoters into proximity to initiate transcription. C_LIO_LI3D genome architecture serves a dual role: enabling acute enhancer-promoter communication and safeguarding long-term lineage fidelity by preventing ectopic gene de-repression. C_LI

genetics↗

bioRxiv2025

Time-resolved phylogenomics analysis reveals patterns in biosphere nutrient limitation through Earth history

The co-evolution of life and Earth has profoundly transformed global biogeochemical cycles over the past 3.5 billion years. These cycles, in turn, have dictated the availability of essential nutrients like phosphorus, nitrogen, and iron, thereby affecting primary productivity and the scale of the Earths biosphere. Despite the critical role of nutrient limitation in shaping the size and scope of the biosphere, significant uncertainties persist about which nutrients were globally limiting at various points in Earth history. Here, we use a phylogenomic approach to trace the origin and spread of genes associated with nutrient limitation over time. We show that genes associated with phosphorus limitation emerged relatively early in lifes history, whereas genes associated with nitrogen limitation emerged later, closer to the Great Oxidation Event. In terms of iron limitation, we present novel evidence that siderophores, compounds that facilitate iron uptake, may have arisen as early as the Archean. Overall, our results have important implications for understanding how the geosphere has influenced the scale and extent of life on Earth for the past 4 billion years.

bioinformatics↗

bioRxiv2025

Xanthomonas type III effector XopN targets scaffold protein OsRACK1B to suppress rice immunity

Bacterial leaf streak (BLS), caused by Xanthomonas oryzae pv. oryzicola (Xoc), is a major bacterial disease that poses a substantial threat to rice production. Although Xoc deploys a variety of effectors to subvert host defenses, the mechanistic basis of how these effectors modulate plant immune signaling remains largely unclear. Here, we show that XopN suppresses rice immune responses and physically interacts with the rice scaffold protein OsRACK1B. Notably, OsRACK1B expression is induced following Xoc infection in a type III secretion system (T3SS)-independent manner. Functional analyses indicate that OsRACK1B overexpression enhances Xoc resistance, whereas loss-of-function mutants exhibit heightened susceptibility. This increased susceptibility is characterized by compromised immunity, including reduced callose deposition, diminished reactive oxygen species (ROS) accumulation, and attenuated expression of defense-related genes such as OsPBZ1 and OsPAL1. Furthermore, we demonstrate that XopN competes with OsRap2.6 for binding to OsRACK1B, thereby disrupting the formation of the OsRACK1B-OsRap2.6 immune complex. These findings reveal a novel virulence strategy in Xoc and identify promising gene targets for developing disease-resistant rice varieties.

plant biology↗

bioRxiv2025

Post-mitotic transcriptional activation and 3D regulatory interactions show locus- and differentiation-specific sensitivity to cohesin depletion

Prior studies showed that structural loops collapse upon acute cohesin depletion, while regulatory enhancer-promoter (E-P) loops largely persist, consistent with minimal transcriptional changes. However, these studies, conducted in asynchronous cells, could not resolve whether cohesin is required for the establishment of regulatory interactions and transcriptional activation during cell division or cell state transitions. To address this gap, we degraded RAD21, a core cohesin subunit, in naive mouse embryonic stem cells (ESCs) transitioning from mitosis to G1 either in self-renewal condition or during differentiation toward formative pluripotency. Although most structural loops failed to be re-established without cohesin, about 35% of regulatory loops reformed at normal or higher frequencies. Cohesin-independent loops showed characteristics of strong active enhancers and promoters and a significant association with H3K27ac mitotic bookmarks. However, inhibition of CBP/p300 during mitotic exit did not impact these cohesin-independent interactions, suggesting the presence of complex compensatory mechanisms. At the transcriptional level, cohesin depletion induced only minor changes, supporting that post-mitotic transcriptional reactivation is largely independent of cohesin. The few genes with impaired reactivation were directly bound by RAD21 at their promoters, engaged in many structural loops, and located within strongly insulated TADs with low gene density. Importantly, degrading cohesin during the M-to-G1 transition in the presence of EpiLC differentiation signals revealed a larger group of susceptible genes, including key signature genes and transcription factors. Impaired activation of these genes was partly due to the failure to establish de novo EpiLC-specific interactions in the absence of cohesin. These experiments revealed locus-specific and context-specific dependencies between cohesin, E-P interactions, and transcription.

molecular biology↗

bioRxiv2024

Neuron-astrocyte Coupling in Lateral Habenula Mediates Depressive-like Behaviors

The lateral habenular (LHb) neurons and astrocytes have been strongly implicated in depression etiology but it was not clear how the two dynamically interact during depression onset. Here, using multi-brain-region calcium photometry recording in freely-moving mice, we discover that stress induces a unique, bimodal neuronal response and a most rapid astrocytic response in the LHb. LHb astrocytic calcium requires the 1A-adrenergic receptor, and depends on a recurrent neural network between the LHb and locus coeruleus (LC). Through the gliotransmitter glutamate and ATP/Adenosine, LHb astrocytes mediate the second-wave activation of local LHb neurons as well as release of norepinephrine (NE). Activation or inhibition LHb astrocytic calcium signaling facilitates or prevents stress-induced depressive-like behaviors respectively. These results identify a stress-induced positive feedback loop in the LHb-LC axis, with astrocytes being a critical signaling relay. The identification of this prominent neuron-glia interaction may shed light on stress management and depression prevention.

neuroscience↗

bioRxiv2024

Tracing the genetic diversity of the bread wheat D genome

Bread wheat (Triticum aestivum) became a globally dominant crop after incorporating the D genome from donor species Aegilops tauschii, while evolutionary history shaping the D genome during this process remains elusive. Here, we proposed a renewed evolutionary model linking Ae. tauschii and hexaploid wheat D genome, based on an ancestral haplotype map covering a total of 762 Ae. tauschii and hexaploid wheat accessions. We dissected the evolutionary process of Ae. tauschii lineages and clarified L3 as the most ancient lineage. A few independent intermediate accessions were reported, demonstrating the low-frequent inter-sublineage geneflow enriched the diversity of Ae. tauschii. We discovered that the D genome of hexaploid wheat inherited from a unified ancestral template, but with a mosaic composition that is highly mixed by three Ae. tauschii L2 sublineages located in the Caspian coastal region, suggesting the early agricultural activities facilitate the innovation of D genome compositions that finalized the success of hexaploidization. We further found that the majority (65.6%) of polymorphisms were attributed to novel mutations absent during the spreading of bread wheat, and also identified large Ae. tauschii introgressions from wild Aegilops lineages, expanding the diversity of wheat D genome and introducing beneficial alleles. This work decoded the mystery of the wheat hexaploidization process and the evolutionary significance of the multi-layered origins of the genetic diversity of the bread wheat D genome.

evolutionary biology↗

bioRxiv2024

Tactile Mechanisms and Afferents Underlying the Rat Pup Transport Response

Juvenile rodents and other altricial mammals react with calming, immobility and folding up of feet to parental pickup, a set of behaviors referred to as transport response. Here we investigate sensory mechanisms underlying the rat transport response. Grasping rat pups in anterior neck positions evokes strong immobility and folding up of feet, whereas more posterior grasping positions have lesser effects on immobility and foot position. Transport responses are enhanced by slow (1Hz) and even more so by fast (4Hz) gentle shaking and translation of the pup, features consistent with parental transport. In response to lateral grasping, the forepaw below the grasping position points downwards and the forepaw lateral to the grasping position points upwards and medially. Such forepaw adjustments put the pups center of gravity below the grasping point, optimizing pup transportability along with folding up of feet and tail lifting. Tactile stimuli on the back, belly, tail, whisker, dorsal forepaws and dorsal hind-paws do not significantly affect the behaviour of anterior-neck-held pups. Instead, ground contact or paw stimulation consistent with ground contact disrupts transport responses. We identify afferents mediating the transport response by examining membrane labelling with FM1-43 following anterior neck grasping. We observe a dense innervation of the anterior neck skin region ([~]30 terminals/ mm2). We also observed an age-related decrease of cytochrome oxidase reactivity in the rat somatosensory cortical neck representation, a possible correlate to the developmental decrease in the pup transport response. We conclude anterior neck grasping and loss of ground contact trigger calming and postural adjustments for parental transport in rat pups, responses putatively driven from the densely innervated anterior neck skin.

neuroscience↗

bioRxiv2024

Deep lipidomic profiling reveals sex dimorphism of lipid metabolism in fibro-calcific aortic valve disease

Fibro-calcific aortic valve disease (FCAVD) is the most common valvular heart disease manifesting in pathological fibro-calcific remodeling of the aortic valve (AV) leaflets, ultimately leading to aortic stenosis. Although lipid dysmetabolism is a driver of FCAVD pathogenesis, the molecular details of the AV lipidome remodeling upon fibrosis and calcification remain largely unknown. Here, we employed advanced lipidomics technologies for deep quantitative profiling of metabolic trajectories in human tricuspid and bicuspid AVs at different pathological stages. Specific extrinsic and intrinsic lipid trends, accompanying the development of fibrosis and calcification, were identified. Importantly, significant differences in lipid signatures between male and female individuals were demonstrated and were attributable to altered sphingolipid metabolism. Taken together, deep lipidomics profiling allowed to identify major molecular events and revealed a high extent of sex-dimorphism in lipidomics signatures of human FCAVD.

pathology↗

bioRxiv2024

Nine high-quality Anas genomes provide new insights into Anas evolution and domestication

The evolutionary origin and genetic architecture of domestic animals are becoming more tractable as the availability of more domestic species genomes. Evolutionary studies of wild and domestic organisms have yielded many fascinating discoveries, while the stories behind the species diversity of Anas or the domestication of duck were largely unknown. Here, we assembled eight chromosome-level Anas genomes. Together with our recently available Pekin duck genome, we investigated Anas phylogeny, genetic differentiation, and gene flow. Extensive phylogenetic inconsistencies were observed in Anas genomes, particularly two phylogeny conflicts between autosome and Z-chromosome. However, the Z chromosome was less impacted by introgression and more suitable to elucidate phylogenetic relationships than autosomes. From the Z-chromosome perspective, we found that the speciation of Anas platyrhynchos and Anas zonorhyncha accompanied with female-biased gene flow, and remodeled duck domestication history. Moreover, we constructed an Anas pan-genome and identified several differentiated SVs between domestic and wild ducks. These SVs might act as repressors/enhancers to regulate their neighboring genes (i.e., GHR and FER), which represented the promising "domestication genes". Additionally, Anas genomes were found being presented LTR retrotransposon bursts, which might largely contribute to functional shifts of genes involved in duck domestication (i.e., MITF and IGF2BP1). This study opens a new window to unravel avian speciation and domestication from Z chromosome.

genomics↗

bioRxiv2024

Recruitment of the m6A/Am demethylase FTO to target RNAs by the telomeric zinc finger protein ZBTB48

N6-methyladenosine (m6A), the most abundant internal modification on eukaryotic mRNA, and N6, 2'-O-dimethyladenosine (m6Am), are epitranscriptomic marks that function in multiple aspects of posttranscriptional regulation. Fat mass and obesity-associated protein (FTO) can remove both m6A and m6Am; however, little is known about how FTO achieves its substrate selectivity. Here, we demonstrate that ZBTB48, a C2H2-zinc finger protein that functions in telomere maintenance, associates with FTO and binds both mRNA and the telomere-associated regulatory RNA TERRA to regulate the functional interactions of FTO with target transcripts. Specifically, depletion of ZBTB48 affects targeting of FTO to sites of m6A/m6Am modification, changes cellular m6A/m6Am levels and, consequently, alters decay rates of target RNAs. ZBTB48 ablation also accelerates growth of HCT-116 colorectal cancer cells and modulates FTO- dependent regulation of Metastasis-associated protein 1 (MTA1) transcripts by controlling the binding to MTA1 mRNA of the m6A reader IGF2BP2. Our findings thus uncover a previously unknown mechanism of posttranscriptional regulation in which ZBTB48 co-ordinates RNA- binding of the m6A/m6Am demethylase FTO to control expression of its target RNAs.

molecular biology↗

bioRxiv2023

Targeted inhibition of BET proteins in HPV-16 associated head and neck squamous cell carcinoma reveals heterogeneous transcription response

Integrated human papillomavirus (HPV-16) associated head and neck squamous cell carcinoma (HNSCC) tumors have worse survival outcomes compared to episomal HPV-16 HNSCC tumors. Therefore, there is a need to differentiate treatment for HPV-16 integrated HNSCC from other viral forms. We analyzed TCGA data and found that HPV+ HNSCC expressed higher transcript levels of the bromodomain and extra terminal domain (BET) family of transcriptional coregulators. However, the mechanism of BET protein-mediated transcription of viral-cellular genes in the integrated viral-HNSCC genomes needs to be better understood. We show that BET inhibition downregulates E6 significantly independent of the viral transcription factor, E2, and there was overall heterogeneity in the downregulation of viral transcription in response to the effects of BET inhibition across HPV-associated cell lines. Chemical BET inhibition was phenocopied with the knockdown of BRD4 and mirrored downregulation of viral E6 and E7 expression. Strikingly, there was heterogeneity in the reactivation of p53 levels despite E6 downregulation, while E7 downregulation did not alter Rb levels significantly. We identified that BET inhibition directly downregulated c-Myc and E2F expression and induced CDKN1A expression. Overall, our studies show that BET inhibition provokes a G1-cell cycle arrest with apoptotic activity and suggests that BET inhibition regulates both viral and cellular gene expression in HPV-associated HNSCC.

cancer biology↗

bioRxiv2023

Serial KinderMiner (SKiM) Discovers and Annotates Biomedical Knowledge Using Co-Occurrence and Transformer Models

BackgroundThe PubMed database contains more than 34 million articles; consequently, it is becoming increasingly difficult for a biomedical researcher to keep up-to-date with different knowledge domains. Computationally efficient and interpretable tools are needed to help researchers find and understand associations between biomedical concepts. The goal of literature-based discovery (LBD) is to connect concepts in isolated literature domains that would normally go undiscovered. This usually takes the form of an A-B-C relationship, where A and C terms are linked through a B term intermediate. Here we describe Serial KinderMiner (SKiM), an LBD algorithm for finding statistically significant links between an A term and one or more C terms through some B term intermediate(s). The development of SKiM is motivated by the the observation that there are only a few LBD tools that provide a functional web interface, and that the available tools are limited in one or more of the following ways: 1) they identify a relationship but not the type of relationship, 2) they do not allow the user to provide their own lists of B or C terms, hindering flexibility, 3) they do not allow for querying thousands of C terms (which is crucial if, for instance, the user wants to query connections between a disease and the thousands of available drugs), or 4) they are specific for a particular biomedical domain (such as cancer). We provide an open-source tool and web interface that improves on all of these issues. ResultsWe demonstrate SKiMs ability to discover useful A-B-C linkages in three control experiments: classic LBD discoveries, drug repurposing, and finding associations related to cancer. Furthermore, we supplement SKiM with a knowledge graph built with transformer machine-learning models to aid in interpreting the relationships between terms found by SKiM. Finally, we provide a simple and intuitive open-source web interface (https://skim.morgridge.org) with comprehensive lists of drugs, diseases, phenotypes, and symptoms so that anyone can easily perform SKiM searches. ConclusionsSKiM is a simple algorithm that can perform LBD searches to discover relationships between arbitrary user-defined concepts. SKiM is generalized for any domain, can perform searches with many thousands of C term concepts, and moves beyond the simple identification of an existence of a relationship; many relationships are given relationship type labels from our knowledge graph.

bioinformatics↗

bioRxiv2022

Pangenome-based dynamic trajectories of intracellular gene transfers in Poaceae unveil a high rate of unceasing integration and selective retention in Triticeae

Intracellular gene transfers (IGTs) between the nucleus and organelles, including plastids and mitochondria, constantly reshapes the nuclear genome during evolution. Despite the substantial contribution of IGTs to genome variation, the dynamic trajectories of IGTs at the pangenomic level remain elusive. Here, we propose a novel approach, IGTminer, to map the evolutionary trajectories of IGTs by collinearity and gene reannotation across multiple genome assemblies. IGTminer was applied to create a nuclear organelle gene (NOG) map across 67 genomes covering 15 Poaceae species, including important crops, revealing the polymorphisms and trajectory dynamics of NOGs. The NOGs produced were verified by experimental evidence and resequencing datasets. We found that most of the NOGs were recently transferred and lineage specific, and that Triticeae species tended to have more NOGs than other Poaceae species. Wheat had a higher retention rate of NOGs than maize and rice, and the retained NOGs were likely involved in the photosynthesis and translation pathways. Large numbers of NOG clusters were aggregated in hexaploid wheat during two rounds of polyploidization and contributed to the genetic diversities among modern wheat varieties. Finally, we proposed a radiocarbon-like model illustrating the transfer and elimination dynamics of NOGs, highlighting the unceasing integration and selective retention of NOGs over evolutionary time. In addition, we implemented an interactive webserver for NOG exploration in Poaceae. In summary, this study provides new resources and clues for the roles of IGTs in shaping inter- and intraspecies genome variation and driving plant genome evolution.

evolutionary biology↗

bioRxiv2022

Chemotherapy drugs induce different gut microbiota disorder pattern and NODs/RIP2/NF-κB signaling pathway activation that lead to different degrees of intestinal injury

5-Fluorouracil (5-FU), irinotecan (CPT-11), oxaliplatin (L-OHP) and calcium folinate (CF) are the widely used chemotherapy drugs to treat colorectal cancer. However, the use of chemotherapy is often accompanied by intestinal inflammation and gut microbiota disorder. Moreover, the change of gut microbiota may lead to destruction of the intestinal barrier, which contributes to the severity of intestinal injury. There was no detailed comparison of intestinal injury and gut microbiota disorder among 5-FU, CPT-11, L-OHP and CF, which is not benefit for the development of targeted detoxification therapy after chemotherapy. In this project, a model of chemotherapy-induced intestinal injury in tumor-bearing mice was established by intraperitoneal injection of chemotherapy drugs at a clinically equivalent dose. 16S rDNA sequencing was used to detect gut microbiota. We found that 5-FU, CPT-11 and L-OHP caused intestinal injury, inflammatory cytokine (IFN-{gamma}, TNF-, IL-1{beta}, and IL-6) secretion, and gut microbiota disorder. Importantly, we established a complex but clear network between the gut microbiota change pattern and intestinal damage degree induced by different chemotherapy drugs. L-OHP caused the most severe damage in intestine and disorder of gut microbiota, and showed considerable overlap of the microbiota change pattern with 5-FU and CPT-11. The phylogenetic investigation of communities by reconstruction of unobserved states, V1.0 (PICRUSt) analysis showed that the microbiota disorder pattern induced by 5-FU, CPT-11 and L-OHP was related to the NOD like signaling pathway. Therefore, we detected the protein expression of the NODs/RIP2/NF-{kappa}B signaling pathway and found that L-OHP activated that pathway highest. Furthermore, by RDA/CCA analysis, we found that Bifidobacterium, Akkermansia, Allobaculum, Catenibacterium, Mucispirillum, Turicibacter, Helicobacter, Proteus, Escherichia Shigella, Alloprevotealla, Vagococcus, Streptococcus and Candidatus Saccharimonas were highly correlated with the NODs/RIP2/NF-{kappa}B signaling pathway, and influenced by chemotherapy drugs. IMPORTANCEThe chemotherapy-induced intestinal injury limit drugs clinical use. Intestinal injury involves multiple signaling pathways and the disruption of microbiota. Our results suggest that the degree of intestinal injury caused by different drugs of the first-line colorectal chemotherapy regimen is related to the change pattern of microbiota. Moreover, the NODs/RIP2/NF-{kappa}B signaling pathway was activated in different degrees is also related to the change pattern of microbiota. We found L-OHP caused the most severe change of gut microbiota, and showed considerable overlap of the microbiota changes pattern with 5-FU and CPT-11. Here, we have established a network of different chemotherapy drugs, gut microbiota and NODs/RIP2/NF-{kappa}B signaling pathway, which may provide a new basis for further elucidating the mechanism and clinical treatment of intestinal injury caused by chemotherapy.

molecular biology↗

bioRxiv2022

SpatialCorr: Identifying Gene Sets with Spatially Varying Correlation Structure

Recent advances in spatially resolved transcriptomics technologies enable both the measurement of genome-wide gene expression profiles and their mapping to spatial locations within a tissue. A first step in spatial transcriptomics data analysis is identifying genes with expression that varies spatially, and robust statistical methods exist to address this challenge. While useful, these methods do not detect spatial changes in the coordinated expression within a group of genes. To this end, we present SpatialCorr, a method for identifying sets of genes with spatially varying correlation structure. Given a collection of gene sets pre-defined by a user, SpatialCorr tests for spatially induced differences in the correlation of each gene set within tissue regions, as well as between and among regions. An application to cutaneous squamous cell carcinoma demonstrates the power of the approach for revealing biological insights not identified using existing methods.

bioinformatics↗

bioRxiv2022

cir-DNA sequencing revealed the landscape of extrachromosomal circular DNA in articular cartilage and the potential roles in osteoarthritis

ObjectiveExtrachromosomal circular DNA (eccDNA) has been shown to be involved in several physiological and pathological processes including immunity, inflammation, aging and tumor. However, the expression of eccDNA in cartilage has been not reported until now. In this study, we aimed to investigate the landscape of eccDNA in articular cartilage and analyze the potential roles in Osteoarthritis (OA). MethodsThe samples of articular cartilage were obtained from total knee arthroplasty (TKA) donors with OA. The mtDNAs (mitochondrial DNA) and the linear DNAs from chondrocytes of articular cartilage were removed. Then the eccDNAs were enriched for cir-DNA sequencing. After quality control evaluation, we systematically revealed the identified eccDNA data including size distribution, the size range and sequence pattern. Moreover, we explored and disscussed the potential roles of eccDNA in OA via motif analysis and GO/KEGG pathways analysis. ResultsThe chondrocytes from OA cartilage contained an abundance of eccDNAs, which was termed as OC-eccDNAs (OA Cartilage-derived eccDNA). The characteristics of OC-eccDNAs were tissue specific, including the distribution, the size range and sequence pattern. Moreover, the functional analysis indicated that eccDNA may be involved in the homeostasis maintenance of chondrocytes and participated in the process of OA. ConclutionsOur data firstly showed the landscape of eccDNA in articular cartilage, and preliminarily indicated the potential roles of eccDNA in OA.

molecular biology↗