Biology subjects

Mao, Q.

Publications and source records attributed to Mao, Q..

At least 19 recordsLinked to original sources

bioRxiv2026

Spatial transcriptomics maps region and isoform specific brain alterations in mdx and mdx4cv models of Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is accompanied by cognitive and neurodevelopmental difficulties. To investigate how the loss of different dystrophin isoforms affects gene expression across brain regions, we performed spatial transcriptomics on brains from mdx and mdx4cv mouse models (lacking Dp427 or Dp427+Dp140 respectively) and healthy controls aged 2 weeks. Both dystrophic models showed transcriptional changes converging on myelin and oligodendrocyte biology and oxidative phosphorylation, but with distinct regional patterns. In mdx mice, myelin genes were upregulated in the amygdala and hippocampus and downregulated in fiber tract regions, while mitochondrial genes were upregulated in most regions but downregulated in the thalamus and isocortex. In mdx4cv mice, myelin genes were broadly upregulated and mitochondrial genes downregulated across almost all regions. Direct comparison between mdx and mdx4cv mice demonstrated that the additional loss of Dp140 expanded localized myelin upregulation across the brain and shifts the mitochondrial response toward widespread downregulation. These differences in regional changes between the mouse models is in line with their dystrophin isoform(s) loss. Our findings provide a molecular basis for the brain-related impairments of DMD and a foundation for future therapeutic studies.

neuroscience↗

bioRxiv2026

Metatranscriptomic surveillance reveals overlooked liver-associated parasite diversity and broad host ranges in small mammals from southern China

Parasite communities in the internal organs of small mammals remain poorly characterized because metatranscriptomic pathogen discovery has largely focused on viruses and bacteria. We individually sequenced liver transcriptomes from 351 small mammals collected across 14 cities in Guangdong Province, China, and combined sequence-based detection with phylogenetic, abundance, transcriptional, and morphological analyses. Parasites were detected in 148 animals (42.2%). Four liver-associated taxa were identified, including three putatively novel or highly divergent lineages. Trichinellidae sp1 dominated the community, occurring in 36.2% of animals (127/351), five host species spanning Rodentia and Eulipotyphla, and all surveyed cities. Hydatigera taeniaeformis occurred in 3.7% (13/351), and its identification was supported by hepatic cysts and morphologically recovered strobilocerci. Eucoccidiorida sp1 and Trypanosoma sp1 were detected sporadically. Mapping to available reference genomes revealed transcripts from multiple genes and functional categories, supporting genuine biological signals rather than isolated marker-gene matches. Amsterdam virus covaried with Trichinellidae sp1 (r = 0.59), whereas Wenzhou tapeworm virus 1 covaried with H. taeniaeformis (r = 0.47). These findings reveal an unexpectedly prevalent, phylogenetically diverse, and broadly distributed liver-associated parasite community and establish individual-organ metatranscriptomics as a useful framework for parasite discovery and surveillance.

microbiology↗

bioRxiv2026

Generalizable Finger Movement Decoding from Intracranial Recordings Across Static and Dynamic Actions

Reliable decoding of finger movements requires brain-computer interfaces (BCIs) that generalize across the diverse static and dynamic actions performed in daily life. Static postures and dynamic movement sequences rely on partially distinct neural representations, and the balance between these components varies widely across tasks. Yet most BCI decoding pipelines are optimized for a narrow task domain, limiting their ability to transfer to new scenarios. Here we show that standard intracranial decoding approaches show notable performance drops when applied to previously unseen finger tasks with different static-dynamic compositions, and that generalization critically depends on multiple elements of the decoding pipeline. High gamma features and short temporal windows yield the most robust cross task transfer. Although nonlinear models perform best when examples of all tasks are represented during training, linear decoders generalize better to novel, particularly dynamic, actions. We identify a consistent static-dynamic structure across tasks that may provide a useful basis for improving generalization. Finally, we show that anatomical heterogeneity between tasks also constrains generalization. Together, these results establish design principles for BCIs that generalize reliably across the rich repertoire of human finger movements.

neuroscience↗

bioRxiv2026

TriMouNet: An Algorithm for Inferring Level-1 Phylogenetic Networks from Multi-Locus Gene Tree Distributions.

With the availability of full genomes of an ever-increasing number of species, many recent phylogenetic analyses have focused on datasets with thousands of loci. In the presence of incomplete lineage sorting (ILS), many gene trees will be discordant with the species tree, which can then be estimated with a supertree method. In a separate stream of research, the reconstruction of phylogenetic networks, which aim to detect and visualize reticulations in addition to the dominant phylogenetic tree, has become common practice. Level-1 networks have the feature that every node can be interpreted as an ancestor of a subset of the taxa of interest and no two distinct cycles share a common node. TriLoNet is a method that constructs a level-1 network on all taxa from 3-taxa networks, so-called trinets. This approach is similar to modern supertree methods, but the trinets are assigned based on a single sequence alignment. Here we present TriMouNet (Trinet Multilocus Network), which uses the tree topology and branch length distribution in gene trees of a multilocus dataset to infer best-fitting trinets, together with scores quantifying their statistical support. These trinets are then puzzled together into a network on all taxa in a TriLoNet fashion. Experiments on simulated and real datasets show that TriMouNet can identify reticulations with low false positive rate, if the gene trees are accurate. On the other hand, TriLoNet applied to the concatenation of all loci, tends to predict wrong reticulations as the consequence of violations of model assumptions.

evolutionary biology↗

bioRxiv2026

Disentangling mucus rheology and transport efficiency in human airways

The protection of the respiratory tract relies on a layer of mucus that is transported along the epithelial surface by the beating of millions of microscopic cilia. This mechanism, called mucociliary clearance, is defective in chronic respiratory diseases. Since these pathologies alter mucus rheology, mucus transport efficiency is hypothesized to rely on its mechanical properties. Yet, this link is difficult to test due to limited experimental models. Here, we introduce an experimental framework that enables us to identify conditions associated with efficient mucus transport or arrest. Strikingly, we show that cilia are able to efficiently propel mucus with properties ranging from a viscoelastic fluid to an elastic solid, revealing that bulk mucus rheology is not the critical determinant of clearance failure. Instead, we demonstrate that the efficiency of mucociliary clearance is governed by the hydration of a thin fluid layer at the cilia-mucus interface. Finally, we use a hydrodynamic model informed by measurements on ciliary beat patterns to infer the properties of this critical layer under both transported and arrested mucus conditions. This work not only offers a novel understanding of the fundamental physical mechanism of mucus transport, but also provides a well-defined and quantitative assay to test effects of mucolytic agents or drugs on mucus clearance.

biophysics↗

bioRxiv2025

Structural and biochemical studies of human PP2A(B55) holoenzyme and ENSA protein complex

The serine/threonine protein phosphatase 2A (B55) holoenzyme (PP2A(B55)), a key cell cycle regulator, is tightly regulated by ENSA, whose phosphorylation at Ser67 inhibits PP2A(B55). The structural basis for how pENSA orchestrates this inhibition to govern mitotic progression remains unclear. In this study, we disapproved the previous hypothesis of direct ENSA-PP2A A subunit interaction, and showed that the ENSA-PP2A(B55) interaction requires the PP2A holoenzyme. We then determined cryo-EM structure of the PP2A(B55)-ENSAS67D complex at 3.03 [A] resolution, which reveals four distinct regions of ENSA, each engaging specific sites on the B55 or C subunits. The structure reveals an extended, inhibited conformation of the PP2A(B55) holoenzyme, which contrasts sharply with the contracted, active state of apo PP2A(B55). pENSA binding induces the C subunit to shift away from the B55 subunit, with the pS67-containing motif inserting into the catalytic site of C subunit and locking the PP2A(B55) holoenzyme in an inactive state. Our work also revealed novel ligand-binding surfaces on B55, and expanded definition of the short linear motif (SliM). Overall, our work provided novel insights into PP2A regulation during cell cycle, and offers new avenues for the discovery of specific PP2A(B55) inhibitors and modulators.

biophysics↗

bioRxiv2025

Regulation of Renal Transporters by Pro-inflammatory Cytokines in Human Proximal Tubular Epithelial Cells: Identification of the Perpetrator and Mechanisms

IntroductionInfection and inflammation elevate circulating pro-inflammatory cytokines that can affect renal drug clearance. Accordingly, we sought to (i) quantify the extent of modulation of renal drug-metabolizing enzymes and transporters (DMETs) by cytokines and (ii) identify the mechanism(s) underlying these effects. MethodsFresh primary human proximal tubular epithelial cells (PTECs) were cultured on extracellular matrix-coated Transwells. PTECs were exposed every 24 h, for 48 h, to IL-6, IL-1{beta}, TNF-, IFN-{gamma}, IL-4, or IL-10 (0.1 or 1 ng/mL), individually or as a cocktail. mRNA expression of 25 renal DMETs was quantified by RT-qPCR. Individual activity of OAT1-4, OCT2, and OCTN1 was measured. To determine mechanisms of these effects, selective MAPK/NF-{kappa}B inhibitors (ERK [PD98059], p38MAPK [SB203580], JNK [SP600125], and NF-{kappa}B [PDTC]), individually or as a cocktail, were used. IL-6, soluble IL-6 receptor (sIL-6R), and IL-6 + sIL-6R were used to probe endogenous/exogenous IL-6 classic versus trans-signaling. ResultsIL-1{beta} was the predominant modulator, downregulating mRNA expression of OAT1-3, OCT2, OAT4, MATE2-K, MRP2, and OATP4C1, and upregulating mRNA expression of OCTN1 and MRP3. TNF- downregulated OAT1-3 mRNA expression to an extent similar to IL-1{beta}, but did not affect other transporters. Activity changes for the major uptake transporters mirrored mRNA directionality. MAPK/NF-{kappa}B blockade by the inhibitor cocktail reduced IL-6 secretion while completely reversing the IL-1{beta}-driven downregulation of OAT1-3 mRNA. JNK inhibition alone restored OAT1/3 mRNA. Inhibition of p38MAPK blunted OAT2 mRNA downregulation. OCTN1 mRNA induction required NF-{kappa}B. Downregulation of OAT4/OCT2 mRNA was largely MAPK/NF-{kappa}B-independent. IL-6 alone, sIL-6R alone, or IL-6 + sIL-6R did not reproduce IL-1{beta}-driven changes in transporter mRNA. ConclusionsIL-1{beta} is the principal driver of cytokine-mediated regulation of human renal transporters in PTECs via JNK/p38MAPK/NF-{kappa}B nodes. These mechanistic, exposure-verified data provide inputs for physiologically based pharmacokinetic predictions of renal secretory clearance and pathway-mediated drug interactions during inflammation. Visual Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/690608v1_ufig1.gif" ALT="Figure 1"> View larger version (64K): org.highwire.dtl.DTLVardef@177e372org.highwire.dtl.DTLVardef@1f56bc4org.highwire.dtl.DTLVardef@17612e3org.highwire.dtl.DTLVardef@d2291f_HPS_FORMAT_FIGEXP M_FIG C_FIG Translational StatementSystemic inflammation increases cytokine concentrations and alters drug pharmacokinetics. Yet, cytokine regulation of renal drug transporters remains poorly defined, even though the kidney clears many anti-infective drugs via active secretion. Using an optimized primary human proximal tubular epithelial cell model that preserves expression and function of major renal transporters, we found that IL-1{beta} is the predominant cytokine that downregulates the mRNA and activity of OAT1-3, OCT2, and OAT4, while upregulating the mRNA and activity of OCTN1. We further showed that IL-1{beta}-driven downregulation of OAT1/3 occurs through JNK signaling, OAT2 through p38MAPK, and OCTN1 through NF-{kappa}B. These data provide quantitative inputs for physiologically based pharmacokinetic models to predict how inflammation alters renal transporter-mediated drug clearance, informing dose adjustment and risk assessment for disease-drug and drug-drug interactions in patients with inflammatory kidney disease or systemic infections. They also highlight signaling nodes where anti-inflammatory therapies might inadvertently modify renal drug transport.

pharmacology and toxicology↗

bioRxiv2025

The transcriptional regulatory circuit as a driver and therapeutic target in CML blast crisis

Patients with blast crisis in chronic myeloid leukemia (CML) exhibit an extremely poor prognosis, with median survival of only a few months and limited therapeutic options. Dysregulated transcriptional regulation plays a pivotal role in driving blast crisis progression. In this study, we performed histone modification and transcriptomic high-throughput sequencing on bone marrow cells derived from chronic and blast-phase CML patients, identifying a CML blast-specific transcriptional regulatory circuit comprising MEF2C, MYB, MEIS1, and ZEB2. These transcription factors (TFs) form protein complexes that co-bind to shared enhancers or promoters, reciprocally enhancing each others transcriptional activity and that of their downstream targets. Mechanistically, this circuit synergistically reprograms chromatin accessibility and transcriptional landscapes in blast cells, parallel activation of purine metabolism and Rho GTPase signaling pathways which exhibit functional crosstalk. Functional validation demonstrated that silencing components of this circuit or its downstream core targets significantly suppressed CML blast progression in vitro and in vivo. Notably, mebendazole (MBZ), a clinically approved inhibitor targeting MYB protein stability, recapitulated these inhibitory effects. Our findings establish the MEF2C-MYB-MEIS1-ZEB2 transcriptional circuit as a central driver of CML blast crisis and position MBZ as a high-potential translational strategy for targeting this lethal phase of the disease. Key PointsO_LIMEF2C, MYB, MEIS1, and ZEB2 form the CML blast-crisis transcriptional circuit, synergistically reprogramming chromatin and transcription. C_LIO_LIMebendazole inhibits CML blast progression by impairing the circuit, offering a rapid translational strategy for this lethal phase. C_LI

cancer biology↗

bioRxiv2025

Evaluating exon-skipping therapies targeting the central nervous system in Duchenne muscular dystrophy using high-resolution spatial transcriptomics

Duchenne muscular dystrophy (DMD) is marked by progressive muscle degeneration due to dystrophin deficiency. Despite cognitive impairments in up to one-third of patients, central nervous system (CNS)-targeted dystrophin restoration remains relatively underexplored compared to muscle-focused therapies. Since dystrophin is expressed in the brain during development and postnatally, it is important to assess which aspects of CNS pathology could be rescued. However, studying Dmd is difficult due to its size, low-abundance transcripts, and with multiple isoforms, limiting the sensitivity and isoform resolution of standard sequencing methods. To overcome these limitations, we applied Xenium spatial transcriptomics to target splice junctions, enabling isoform-specific and exon 51 skipping events detection across brain regions and cell types. Using this approach, we analyzed mdx52 mice lacking the full-length and Dp140 isoforms, treated with two exon 51 skipping therapies (antisense oligonucleotides or AAV-U7ex51). We observed distinct spatial expression patterns in the wild type brain between the full-length isoforms (Dp427c/m/p1) and shorter isoforms (Dp71 and Dp40). The full-length isoforms were predominantly expressed in cortex layers 2/3-6b and the CA1 region, while the shorter isoforms were localized to cortex layer 1 and the dentate gyrus. Among the exon skipping therapies tested, U7ex51 delivered neonatally induced broad exon skipping in neurons and effectively restored full-length isoforms in the targeted cells. This study introduces the first subcellular-resolution spatial transcriptomic atlas of dystrophin presence and rescue in the CNS and demonstrates a framework for evaluating gene therapies in spatially and transcriptionally complex tissues such as the brain.

neuroscience↗

bioRxiv2025

AlphaFold3 for Non-canonical Cyclic Peptide Modeling: Hierarchical Benchmarking Reveals Accuracy and Practical Guidelines

Despite the revolutionary impact of AlphaFold3 on structural biology, this models capability in predicting non-canonical cyclic peptides remains unexplored. Given the clinical significance of cyclic peptides containing unnatural residues as a therapeutic modality, we present the first systematic evaluation of AlphaFold3 for this class of molecules. To facilitate benchmarking, we developed an automated input pipeline to streamline AlphaFold3 predictions for cyclic peptides. Our study aims to: (1) quantify the hierarchical accuracy (all-atoms, C atoms, and atoms of unnatural residue levels) of AlphaFold3 in predicting both non-canonical cyclic peptide monomers and complexes; (2) assess the reliability of AlphaFold3s confidence metrics; (3) evaluate the influence of multiple sequence alignment (MSA) and structural templates; and (4) identify systematic biases in AlphaFold3s predictions. Based on these analyses, we provide practical guidelines for applying AlphaFold3 in cyclic peptide structure prediction for facilitating the related research of bioactive cyclic peptides.

bioinformatics↗

bioRxiv2025

Genetically Defined Organoid Models Reveal Mechanisms Driving Squamous Cell Neoplastic Evolution and Identify Potential Therapeutic Vulnerabilities

Upper aerodigestive squamous cell carcinoma (UASCC) is an aggressive and lethal neoplasm, with its early neoplastic transformation mechanisms remaining poorly understood. Here, we characterize over 25 genetically-defined organoid models derived from murine and human oral/esophageal tissues harboring key driver mutations. Double knockout of TP53 and CDKN2A induced morphological dysplasia, hyperproliferation, loss of squamous differentiation, and tumorigenicity, which were further exacerbated by additional driver mutations (e.g., PIK3CA, NOTCH1, KMT2C). Single-cell analysis revealed an expansion of quiescent basal cells and proliferative squamous cells, alongside a loss of differentiated squamous cells during malignant transformation. A distinct senescence program, regulated by ANXA1, was markedly diminished during early neoplastic evolution. Mechanistically, the ANXA1-SMAD3-p27KIP1 pathway was identified as a critical regulator of this senescence program, acting to suppress neoplastic features in organoid models. Lastly, our high-throughput, single-organoid-resolution drug screens unexpectedly revealed PIK3CA-driven organoids exhibited sensitivity to Mitomycin C and Onalespib. This study provides novel mechanistic insights into early neoplastic evolution and underscores the value of genetically-defined organoid models for investigating cancer biology and identifying targeted therapies.

cancer biology↗

bioRxiv2024

NCPepFold: Accurate Prediction of Non-canonical Cyclic Peptide Structures via Cyclization Optimization with Multigranular Representation

Artificial intelligence-based peptide structure prediction methods have revolutionized biomolecular science. However, restricting predictions to peptides composed solely of 20 natural amino acids significantly limits their practical application, as such peptides often demonstrate poor stability under physiological conditions. Here, we present NCPepFold, a computational approach that can utilize a specific cyclic position matrix to directly predict the structure of cyclic peptides with non-canonical amino acids. By integrating multi-granularity information at the residue- and atomic-level, along with fine-tuning techniques, NCPepFold significantly improves prediction accuracy, with the average peptide RMSD for cyclic peptides being 1.640 [A]. In summary, this is a novel deep learning model designed specifically for cyclic peptides with non-canonical amino acids without length restrictions, offering great potential for peptide drug design and advancing biomedical research.

bioinformatics↗

bioRxiv2024

Genomic and single-cell characterization of patient-derived tumor organoid models of head and neck squamous cell carcinoma

Head and Neck Squamous Cell Carcinoma (HNSCC) remains a significant health burden due to tumor heterogeneity and treatment resistance, emphasizing the need for improved biological understanding and tailored therapies. This study enrolled 31 HNSCC patients for the establishment of patient-derived tumor organoids (PDOs), which faithfully maintained genomic features and histopathological traits of primary tumors. Long-term culture preserved key characteristics, affirming PDOs as robust representative models. PDOs demonstrated predictive capability for cisplatin treatment responses, correlating ex vivo drug sensitivity with patient outcomes. Bulk and single-cell RNA sequencing unveiled molecular subtypes and intratumor heterogeneity (ITH) in PDOs, paralleling patient tumors. Notably, a hybrid epithelial-mesenchymal transition (hEMT)-like ITH program is associated with cisplatin resistance and poor patient survival. Functional analyses identified amphiregulin (AREG) as a potential regulator of the hybrid epithelial/mesenchymal state. Moreover, AREG contributes to cisplatin resistance via EGFR pathway activation, corroborated by clinical samples. In summary, HNSCC PDOs serve as reliable and versatile models, offer predictive insights into ITH programs and treatment responses, and uncover potential therapeutic targets for personalized medicine. One Sentence SummaryThis study establishes patient-derived tumor organoids (PDOs) from 31 Head and Neck Squamous Cell Carcinoma (HNSCC) patients, faithfully recapitulating characteristics of primary tumors and accurately predicting clinical responses to cisplatin treatment. We reveal intertumoral heterogeneity within PDOs and a hybrid epithelial-mesenchymal transition (hEMT) program conferring cisplatin resistance, highlighting amphiregulin (AREG) as a regulator of cellular plasticity and potential therapeutic target for HNSCC treatment.

cancer biology↗

bioRxiv2024

Brochosomes as an antireflective camouflage coating for leafhoppers

In nature, insects face immense predation pressure, where visual cues play a vital role in predators locating them. To counter this threat, insects employ a variety of nano- and microstructures on their cuticular layer to manipulate and interact with light, enhancing anti-reflective properties and providing camouflage or reducing detectability by predators. Leafhoppers have a unique extra-cuticular coating called brochosome, yet its anti-reflective functions and protein composition remain unclear. Our study demonstrates strong anti-reflective properties of brochosomes, effectively reducing reflectance on the cuticle surface, especially in the ultraviolet spectrum, to improve evasion from visual predators. Furthermore, we identify four novel structural proteins of the brochosome (BSM) for the first time. Inhibiting their synthesis by RNAi alters brochosome morphology, impacting the optical properties of the cuticle surface. Evolutionary origin analysis of BSM suggests that brochosomes likely originated from a process involving duplication-divergence. Our study reveals that leafhoppers employ a unique camouflage strategy by secreting brochosomes as anti-reflection nano-coatings, enabling them to evade natural predators and contributing to their evolutionary success.

ecology↗

bioRxiv2024

Glioma-associated fibroblasts promote glioblastoma resistance to temozolomide through CCL2-CCR2 paracrine signaling

Complicated tumor microenvironment contributes mostly to chemoresistance in glioblastoma. Glioma-associated fibroblasts (GAFs) were recently identified as non-tumor stromal cells in the glioblastoma microenvironment, whereas their function in glioblastoma chemoresistance is unclear. Herein, we interrogated the correlation between GAFs and chemoresistance of glioblastoma by examining a series of patient-derived GAFs and glioblastoma organoids (GBOs), revealing that GAFs could promote temozolomide resistance in glioblastoma. Mechanistically, C-C motif chemokine ligand 2 (CCL2) secreted by GAFs selectively activated the ERK1/2 signaling in glioblastoma cells to potentiate temozolomide resistance. Pharmacologically disrupting the CCL2-CCR2 axis or MEK1/2-ERK1/2 pathway effectively improved the therapeutic efficacy of temozolomide in GBM cells and patient-derived GBOs, and both decreased phospho-ERK1/2 expression. Collectively, our results identified that targeting the GAF-dominated CCL2-ERK1/2 pathway may be an alternative strategy to alleviate the GAF-mediated chemoresistance of glioblastoma. SignificanceComprehensive interpretation of the mutual support between tumor microenvironment and cancer cells is demanded for glioma with poor response rates to chemotherapy. This study demonstrates that GAFs promote the temozolomide resistance of glioblastoma by secreting cytokine CCL2 to activate ERK1/2 pathway, which may serve as a potential druggable candidate. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/581575v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@167b955org.highwire.dtl.DTLVardef@b892bcorg.highwire.dtl.DTLVardef@1a9b082org.highwire.dtl.DTLVardef@18327a8_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphic abstract.C_FLOATNO Schematic illustration for GAFs mediated chemoresistance of GBMs and underlying mechanisms. We demonstrate that Glioma-associated Fibroblasts (GAFs) grow in gliomas by isolating and identifying a panel of patient-derived GAFs. CCL2 secreted by GAFs stimulates CCR2 in GBM cells, which promotes activation of the ERK1/2 expression to potentiate GBM chemoresistance. C_FIG

cancer biology↗

bioRxiv2024

IOBR2: Multidimensional Decoding Tumor Microenvironment for Immuno-Oncology Research

The use of large transcriptome datasets has greatly improved our understanding of the tumor microenvironment (TME) and helped develop precise immunotherapies. The increasing popularity of multi-omics sequencing, single-cell transcriptome sequencing (scRNA), and spatial transcriptome sequencing has led to numerous new discoveries. However, these findings require clinical phenotypic validation with a large sample size. To enhance the integration of multi-omics in advancing research on the tumor microenvironment, we have developed a systematic and comprehensive analytical tool (Immuno-Oncology Biological Research 2, IOBR2) based on our prior work. IOBR2 offers six modules for TME analysis based on multi-omics data. These modules cover data preprocessing, TME estimation, TME infiltrating patterns, cellular interactions, genome and TME interaction, and visualization for TME relevant features, as well as modelling based on key features. IOBR2 integrates multiple vital microenvironmental analysis algorithms and signature estimation methods, simplifying the analysis and downstream visualization of the TME. In addition to providing a quick and easy way to construct gene signatures from single-cell data, IOBR2 also provides a way to construct a reference matrix for TME deconvolution from single-cell RNAseq. The analysis pipeline and feature visualization are user-friendly and provide a comprehensive description of the complex TME, offering insights into tumor-immune interactions. A comprehensive gitbook (https://iobr.github.io/book/) is available with a user-friendly manual and complete analysis workflow for each module.

cancer biology↗

bioRxiv2023

Assembly and analysis of the genome of Notholithocarpus densiflorus

Tanoak (Notholithocarpus densiflorus) is an evergreen tree in the Fagaceae family found in California and southern Oregon. Historically, tanoak acorns were an important food source for Native American tribes and the bark was used extensively in the leather tanning process. Long considered a disjunct relictual element of the Asian stone oaks (Lithocarpus spp.), phylogenetic analysis has determined that the tanoak is an example of convergent evolution. Tanoaks are deeply divergent from oaks (Quercus) of the Pacific Northwest and comprise a new genus with a single species. These trees are highly susceptible to sudden oak death (SOD), a plant pathogen (Phytophthora ramorum) that has caused widespread mortality of tanoaks. Here, we set out to assemble the genome and perform comparative studies among a number of individuals that demonstrated varying levels of susceptibility to SOD. First, we sequenced and de novo assembled a draft reference genome of N. densiflorus using co-barcoded library processing methods and an MGI DNBSEQ-G400 sequencer. To increase the contiguity of the final assembly, we also sequenced Oxford Nanopore (ONT) long reads to 30X coverage. To our knowledge, the draft genome reported here is one of the more contiguous and complete genomes of a tree species published until now, with a contig N50 of [~]1.2 Mb and a scaffold N50 of [~]2.1 Mb. In addition, we sequenced 11 genetically distinct individuals and mapped these onto the draft reference genome enabling the discovery of almost 25 million single nucleotide polymorphisms and [~]4.4 million small insertions and deletions. Finally, using co-barcoded data we were able to generate complete haplotype coverage of all 11 genomes.

genomics↗

bioRxiv2022

FAM76B regulates NF-κB-mediated inflammatory pathway by influencing the translocation of hnRNPA2B1

FAM76B has been reported to be a nuclear speckle localized protein with unknown function. In this study, FAM76B was first demonstrated to inhibit the NF-{kappa}B-mediated inflammatory pathway by affecting the translocation of hnRNPA2B1 in vitro. We further showed that FAM76B suppressed inflammation by regulating the NF-{kappa}B pathway in vivo using a traumatic brain injury (TBI) model in FAM76B knockout mice. Lastly, FAM76B was shown to interact with hnRNPA2B1 in human tissues taken from patients with acute, organizing, and chronic TBI, and with different neurodegenerative diseases. The results suggested that FAM76B mediates neuroinflammation by influencing the translocation of hnRNPA2B1 in vivo during TBI repair and neurodegenerative diseases. In summary, we for the first time demonstrated the role of FAM76B in regulating inflammation and further showed that FAM76B could regulate the NF-{kappa}B-mediated inflammatory pathway by affecting hnRNPA2B1 translocation, which provides new information for studying the mechanism of inflammation regulation.

cell biology↗