Biology subjects

Ruan, J.

Publications and source records attributed to Ruan, J..

At least 37 records · Page 2Linked to original sources

bioRxiv2024

TMEM63B functions as a mammalian thirst receptor

Thirst drives animals to reinstate water homeostasis by fluid intake. An increase of blood osmolality is thought to induce thirst by activating a thirst receptor expressed in the subfornical organ (SFO), but the molecular identity of this receptor remains elusive. Here, we provide behavioral and functional evidence to show that TMEM63B functions as a mammalian thirst receptor in the SFO and mediates osmotic and dehydrated thirst. First, we showed that TMEM63B is expressed in SFO excitatory neurons and required for the neuronal responses to hypertonic stimulation. Heterologously expressed TMEM63B is activated by hypertonic stimuli and point mutations can alter the reversal potential of the channel. More importantly, purified TMEM63B in liposomes establishes osmolarity-gated currents. Finally, Tmem63b knockout mice have profound deficits in thirst, and deleting TMEM63B within the SFO neurons recapitulated this phenotype. Taken together, these results provide a molecular basis for thirst 82and demonstrate TMEM63B is the long-sought mammalian thirst receptor.

neuroscience↗

bioRxiv2024

BSAlign: a library for nucleotide sequence alignment

Increasing the accuracy of the nucleotide sequence alignment is an essential issue in genomics research. Although classic dynamic-programming algorithms (e.g., Smith-Waterman and Needleman-Wunsch) guarantee to produce the optimal result, their time complexity hinders the application of large-scale sequence alignment. Many optimization efforts that aim to accelerate the alignment process generally come from three perspectives: re-designing data structures (e.g., diagonal or striped Single Instruction Multiple Data (SIMD) implementations), increasing the number of parallelisms in SIMD operations (e.g., difference recurrence relation), or reducing searching space (e.g., banded dynamic programming). However, no methods combine all these three aspects to build an ultra-fast algorithm. We have developed a Banded Striped Aligner(library) named BSAlign that delivers accurate alignment results at an ultra-fast speed by knitting a series of novel methods together to take advantage of all of the aforementioned three perspectives with highlights such as active F-loop in striped vectorization and striped move in banded dynamic programming. We applied our new acceleration design on both regular and edit-distance pairwise alignment. BSAlign achieved 2-fold speed-up than other SIMD based implementations for regular pairwise alignment, and 1.5 to 4-fold speedup in edit distance based implementations for long reads. BSAlign is implemented in C programing language and is available at https://github.com/ruanjue/bsalign.

bioinformatics↗

bioRxiv2024

Recognition and localization of maize leaves in RGB images based on Point-Line Net

Plant phenotype detection plays a crucial role in understanding and studying plant biology, agriculture, and ecology. It involves the quantification and analysis of various physical traits and characteristics of plants, such as plant height, leaf shape, angle, number, and growth trajectory. By accurately detecting and measuring these phenotypic traits, researchers can gain insights into plant growth, development, stress tolerance, and the influence of environmental factors. Among these phenotypic information, the number of leaves and growth trajectory of the plant are more accessible. Nonetheless, obtaining these information is labor-intensive and financially demanding. With the rapid development of computer vision technology and artificial intelligence, using maize field images to fully analyze plant-related information such as growth trajectory and number of leaves can greatly eliminate repetitive labor work and enhance the efficiency of plant breeding. However, the application of deep learning methods still faces challenges due to the serious occlusion problem and complex background of field plant images. In this study, we developed a deep learning method called Point-Line Net, which is based on the Mask R-CNN frame-work, to automatically recognize maize field images and determine the number and growth trajectory of leaves and roots. The experimental results demonstrate that the object detection accuracy (mAP) of our Point-Line Net can reach 81.5%. Moreover, to describe the position and growth of leaves and roots, we introduced a new lightweight "keypoint" detection branch that achieved 33.5 using our custom distance verification index. Overall, these findings provide valuable insights for future field plant phenotype detection, particularly for the datasets with dot and line annotations.

plant biology↗

bioRxiv2023

Ca2+ Oscillation in Vascular Smooth Muscle Cells Control Myogenic Spontaneous Vasomotion and Counteract Post-ischemic No-reflow

Ischemic stroke produces the highest adult disability. Despite successful recanalization, no-reflow, or the futile restoration of the cerebral perfusion after ischemia, is a major cause of brain lesion expansion. However, the vascular mechanism underlying this hypoperfusion is largely unknown, and no approach is available to actively promote optimal reperfusion to treat no-reflow. Here, by combining two-photon laser scanning microscopy (2PLSM) and a mouse middle cerebral arteriolar occlusion (MCAO) model, we found myogenic vasomotion deficits correlated with post-ischemic cerebral circulation interruptions and no-reflow. Transient occlusion-induced transient loss of mitochondrial membrane potential ({Delta}{Psi}m) permanently impaired mitochondria-endoplasmic reticulum (ER) contacts and abolished Ca2+ oscillation in smooth muscle cells (SMCs), the driving force of myogenic spontaneous vasomotion. Furthermore, tethering mitochondria and ER by specific overexpression of ME-Linker in SMCs restored cytosolic Ca2+ homeostasis, remotivated myogenic spontaneous vasomotion, achieved optimal reperfusion, and ameliorated neurological injury. Collectively, the maintaining of arteriolar myogenic vasomotion and mitochondria-ER contacts in SMCs, are of critical importance in preventing post-ischemic no-reflow.

neuroscience↗

bioRxiv2023

Two subtypes of GTPase-activating proteins coordinate tip growth and cell size regulation in Physcomitrium patens

The establishment of cell polarity is a prerequisite for many developmental processes. However, how it is achieved during tip growth in plants remains elusive. Here, we show that the RHO OF PLANTs (ROPs), ROP GUANINE NUCLEOTIDE EXCHANGE FACTORs (RopGEFs), and ROP GTPASE-ACTIVATING PROTEINs (RopGAPs) assemble into membrane domains in tip-growing cells of the moss Physcomitrium patens. The confinement of membrane domains requires redundant global inactivation of ROPs by PpRopGAPs and the PLECKSTRIN HOMOLOGY (PH) domain-containing RenGAP PpREN. Unexpectedly, PpRopGAPs and PpREN exert opposing effects on domain size and cell width upon overexpression. Biochemical and functional analyses indicate that PpRopGAPs are recruited to the membrane by active ROPs to restrict domain size through clustering, whereas PpREN rapidly inactivates ROPs and inhibits PpRopGAP-induced clustering. We propose that the activity- and clustering-based domain organization by RopGAPs and RenGAPs is a general mechanism for coordinating polarized cell growth and cell size regulation in plants. SignificanceUsing the moss Physcomitrium patens, we show that PpRopGAPs and PpRenGAP redundantly regulate tip growth by inactivating ROP GTPases and influencing their membrane organization. They display distinct GAP activities and binding capacities to ROPs and could oppositely regulate cell width when overexpressed. We propose that tip growth and cell size regulation are coordinated by two subtypes of GTPase-activating proteins that act together to maintain an optimal amount of active ROPs but reversely regulate the membrane clustering of ROPs. The involvement of functionally diverged GAPs in modulating ROP activity and localization may represent a general mechanism for cell morphology regulation in plants.

plant biology↗

bioRxiv2023

Karyopherin mimicry explains how the HIV capsid penetrates nuclear pores

Summary ParagraphHIV can infect non-dividing cells because the viral capsid can overcome the selective barrier of the nuclear pore complex and deliver the genome directly into the nucleus. Remarkably, the intact HIV capsid is over one thousand times greater than the size-limit prescribed by the nuclear pores diffusion barrier. This barrier is a phase-separated condensate in the central channel of the nuclear pore and is comprised of intrinsically-disordered nucleoporin domains enriched in phenylalanine-glycine (FG) dipeptides. Through multivalent FG-interactions, cellular karyopherins and their bound cargoes solubilise in this phase to drive nucleocytoplasmic transport. By performing an in vitro dissection of the nuclear pore complex, we show that a pocket on the surface of the HIV capsid similarly interacts with FG-motifs from multiple nucleoporins and that this interaction licenses capsids to penetrate nucleoporin condensates. This karyopherin mimicry model resolves a key conceptual challenge for the role of the HIV capsid in nuclear entry, and explains how an exogenous entity much larger than any known cellular cargo can non-destructively breach the nuclear envelope.

biochemistry↗

bioRxiv2023

An efficient error correction and accurate assembly tool for noisy long reads

Long read sequencing data, particularly those derived from the Oxford Nanopore (ONT) sequencing platform, tend to exhibit a high error rate. Here, we present NextDenovo, a highly efficient error correction and assembly tool for noisy long reads, which achieves a high level of accuracy in genome assembly. NextDenovo can rapidly correct reads; these corrected reads contain fewer errors than other comparable tools and are characterized by fewer chimeric alignments. We applied NextDenovo to the assembly of high quality reference genomes of 35 diverse humans from across the world using ONT Nanopore long read sequencing data. Based on these de novo genome assemblies, we were able to identify the landscape of segmental duplications and gene copy number variation in the modern human population. The use of the NextDenovo program should pave the way for population-scale long-read assembly, thereby facilitating the construction of human pan-genomes, using Nanopore long read sequencing data.

bioinformatics↗

bioRxiv2023

Neurovascular Coupling is Required for Amygdala Neuronal Activation and Associated Emotional Behaviors in Mice, Depending on NMDA Receptor Subunit 2D-expressing Cerebral Arteriolar Smooth Muscle Cells

Emotion induces changes in regional cerebral blood flow (CBF), a manifestation of neurovascular coupling (NVC), yet whether NVC might feed back to modulate emotion actively remains unexplored. Here, we demonstrate that NVC actively and bidirectionally modulates stress-induced negative emotions. We established bidirectional manipulations of NVC in freely moving mice by employing integrated pharmacological, genetic, and arteriolar optogenetic approaches. Our results showed that both systemic and basolateral amygdala (BLA) region-specific NVC deficiencies heightened emotional responses when mice transitioned from a safe, familiar environment to anxiogenic environments, and local restoration of NVC in the BLA normalized these responses. Mechanistically, NVC dysfunction impairs the capacity of BLA neuronal scaling during state transitions, manifesting as a characteristic biphasic pattern of c-Fos topology. Namely, the NVC-deficient animal aberrantly adopts high-stress configurations under mild stress but regresses to low-stress templates during high-demand survival threats, thereby compromising defensive sustainability. Notably, the genetic NVC-enhancement model counteracts NVC impairments caused by chronic stress, thereby alleviating stress-driven emotional distress. These findings established NVC in the BLA as an allostatic program that fine-tunes neural circuit activity for emotional responses, with implications for understanding and treating emotional disorders.

neuroscience↗

bioRxiv2022

Precision super-resolution cryo-correlative light and electron microscopy for rapid in situ structural analyses of optogenetically-positioned organelles

Unambiguous targeting of cellular structures for in situ cryo-electron microscopy in the heterogeneous, dense, and compacted environment of the cytoplasm remains challenging. Here we have developed a novel cryogenic correlative light and electron microscopy (cryo-CLEM) workflow which combines thin cells grown on a mechanically defined substratum to rapidly analyse organelles and macromolecular complexes in the cell by cryo-electron tomography (cryo-ET). We coupled these advancements with optogenetics to redistribute perinuclear-localised organelles to the cell periphery for cryo-ET. This reliable and robust workflow allows for fast in situ analyses without the requirement for cryo-focused ion beam milling. We have developed a protocol where cells can be frozen, imaged by cryo-fluorescence microscopy and ready for batch cryo-ET within a day.

cell biology↗

bioRxiv2022

Haplotype-resolved assemblies and variant benchmark of a Chinese Quartet

As the state-of-the-art sequencing technologies and computational methods enable investigation of challenging regions in the human genome, an update variant benchmark is demanded. Herein, we sequenced a Chinese Quartet, consisting of two monozygotic twin daughters and their biological parents, with multiple advanced sequencing platforms, including Illumina, BGI, PacBio, and Oxford Nanopore Technology. We phased the long reads of the monozygotic twin daughters into paternal and maternal haplotypes using the parent-child genetic map. For each haplotype, we utilized advanced long reads to generate haplotype-resolved assemblies (HRAs) with high accuracy, completeness, and continuity. Based on the ingenious quartet samples, novel computational methods, high-quality sequencing reads, and HRAs, we established a comprehensive variant benchmark, including 3,883,283 SNVs, 859,256 Indels, 9,678 large deletions, 15,324 large insertions, 40 inversions, and 31 complex structural variants shared between the monozygotic twin daughters. In particular, the preciously excluded regions, such as repeat regions and the human leukocyte antigen (HLA) region, were systematically examined. Finally, we illustrated how the sequencing depth correlated with the de novo assembly and variant detection, from which we learned that 30 x HiFi is a balance between performance and cost. In summary, this study provides high-quality haplotype-resolved assemblies and a variant benchmark for two Chinese monozygotic twin samples. The benchmark expanded the regions of the previous report and adapted to the evolving sequencing technologies and computational methods.

genomics↗

bioRxiv2022

Neuroinflammation in neuronopathic Gaucher disease: Role of microglia and NK cells

BackgroundNeuronopathic Gaucher Disease (nGD) is a rare neurodegenerative disorder caused by biallelic mutations in Gba, and buildup of glycosphingolipids in lysosomes. Neuronal injury and cell death are prominent pathological features, however the role of Gba in individual cell types and involvement of microglia, blood derived macrophages and immune infiltrates in nGD pathology remains enigmatic. MethodsHere, using single cell resolution of mouse nGD brains, we found induction of neuroinflammation pathways involving microglia, NK cells, astrocytes, and neurons. ResultsTargeted rescue of Gba in microglia and in neurons, respectively in Gba deficient, nGD mice reversed the buildup of glucosylceramide (GlcCer) and glucosylsphingosine (GlcSph), concomitant with amelioration of neuroinflammation, reduced level of serum neurofilament light chain (Nf-L) and improved survival. The levels of bioactive lipid, GlcSph was strongly correlated with serum Nf-L and ApoE in nGD mouse models as well as GD patients. Gba rescue in microglia/macrophage compartment prolonged survival, that was further enhanced upon treatment with brain permeant inhibitor of glucosylceramide synthase, effects mediated via improved glycosphingolipid homeostasis and reversal of neuroinflammation involving activation of microglia, brain macrophages and NK cells. ConclusionsTogether, our study delineates individual cellular effects of Gba deficiency in nGD brains, highlighting the central role of neuroinflammation driven by microglia activation and the role of brain permeant small molecule glucosylceramide inhibitor in reversing complex multidimensional pathophysiology of nGD. Our findings advance disease biology whilst identifying compelling biomarkers of nGD to improve patient management, enrich clinical trials and illuminate therapeutic targets. FundingResearch grant from Sanofi Genzyme; other support includes R01NS110354.Yale Liver Center P30DK034989, pilot project grant.

immunology↗

bioRxiv2022

Loss of the chromatin remodeler, ATRX, promotes aggressive features of osteosarcoma with increased NF-κB signaling and integrin receptor binding

Osteosarcoma (OS) is a lethal disease with few known targeted therapies. Here we show that decreased ATRX expression is associated with more aggressive tumor cell phenotypes, including increased growth, migration, invasion, and metastasis. These phenotypic changes correspond with activation of NF-{kappa}B signaling, extracellular matrix remodeling, increased integrin v{beta}3 expression, and ETS family transcription factor binding. Here we characterize these changes in vitro, in vivo, and in a dataset of human OS patients. This increased aggression substantially sensitizes ATRX-deficient OS cells to integrin signaling inhibition. Thus, ATRX plays an important tumor suppression role in OS, and loss of function of this gene may underlie new therapeutic vulnerabilities. The relationship between ATRX expression and integrin binding, NF-{kappa}B activation, and ETS family transcription factor binding has not been described in previous studies and may impact the pathophysiology of other diseases with ATRX loss, including other cancers and the ATR-X alpha thalassemia mental retardation syndrome.

cancer biology↗

bioRxiv2022

Blood-brain barrier permeability to enrofloxacin in Pengze crucian carp (Carassius auratus var. Pengze)

To explore the permeability of blood-brain barrier (BBB) to enrofloxacin (ENR) and the role of brain injury markers in the evaluation of brain damage, crucian carp (Carassius auratus var. Pengze) was employed in this work as the research object treated by a single oral administration of the antibiotic. Results showed that ENR residues could be detected in brain of crucian carp exposed to both half lethal dose (LD50) and safe dose (SD) of ENR throughout the trial period, indicating that ENR had an ability of permeating the BBB of crucian carp. Evans blue (EB) dispersively distributed in brain tissue of fish exposed to SD ENR, but not in the vehicle-treated fish brain, which suggested structural failure of BBB by ENR. Expression levels of BBB-related molecules, occludin and P-glycoprotein (P-gp), were significantly down-regulated by ENR. Brain injury markers, NSE, S100B and GFAP were improved that were demonstrated by elevated contents of proteins in brain and serum. According to the data of correlation analysis, it was observed that ENR residue was closely related to S100B and GFAP, indicating that S100B and GFAP could be used as evaluation indicators for brain injury of crucian carp. All findings mentioned above suggest that ENR may cause structural change of BBB, resulting in biological brain damage in crucian carp.

pharmacology and toxicology↗

bioRxiv2021

Rapid visual CRISPR assay: a naked-eye colorimetric detection method for nucleic acids based on CRISPR/Cas12a and convolutional neural network

Rapid diagnosis based on naked-eye colorimetric detection remains challenging, but it could build new capacities for molecular point-of-care testing (POCT). In this study, we evaluated the performance of 16 types of single-stranded DNA-fluorophore-quencher (ssDNA-FQ) reporters for use with CRISPR/Cas12a based visual colorimetric assays. Among them, 9 ssDNA-FQ reporters were found to be suitable for direct visual colorimetric detection, with especially very strong performance using ROX-labeled reporters. We optimized the reaction concentrations of these ssDNA-FQ reporters for naked-eye read-out of assay results (no transducing component required for visualization). Subsequently, we developed a convolutional neural network algorithm standardize and to automate the analytical colorimetric assessment of images and integrated this into the MagicEye mobile phone software. A field-deployable assay platform named RApid VIsual CRISPR (RAVI-CRISPR) based on a ROX-labeled reporter with isothermal amplification and CRISPR/Cas12a targeting was established. We deployed RAVI-CRISPR in a single tube towards an instrument-less colorimetric POCT format that requires only a portable rechargeable hand warmer for incubation. The RAVI-CRISPR was successfully used for the single-copy detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and African swine fever virus (ASFV). Our study demonstrates this novel RAVI-CRISPR system for distinguishing different pathogenic nucleic acid targets with high specificity and sensitivity as the simplest-to-date platform for rapid pen-side testing.

molecular biology↗

bioRxiv2021

A completely parameter-free method for graph-based single cell RNA-seq clustering

Single-cell RNA sequencing (scRNAseq) offers an unprecedented potential for scrutinizing complex biological systems at single cell resolution. One of the most important applications of scRNAseq is to cluster cells into groups of similar expression profiles, which allows unsupervised identification of novel cell subtypes. While many clustering algorithms have been tested towards this goal, graph-based algorithms appear to be the most effective, due to their ability to accommodate the sparsity of the data, as well as the complex topology of the cell population. An integral part of almost all such clustering methods is the construction of a k-nearest-neighbor (KNN) network, and the choice of k, implicitly or explicitly, can have a profound impact on the density distribution of the graph and the structure of the resulting clusters, as well as the resolution of clusters that one can successfully identify from the data. In this work, we propose a fairly simple but robust approach to estimate the best k for constructing the KNN graph while simultaneously identifying the optimal clustering structure from the graph. Our method, named scQcut, employs a topology-based criterion to guide the construction of KNN graph, and then applies an efficient modularity-based community discovery algorithm to predict robust cell clusters. The results obtained from applying scQcut on a large number of real and synthetic datasets demonstrated that scQcut --which does not require any user-tuned parameters--outperformed several popular state-of-the-art clustering methods in terms of clustering accuracy and the ability to correctly identify rare cell types. The promising results indicate that an accurate approximation of the parameter k, which determines the topology of the network, is a crucial element of a successful graph-based clustering method to recover the final community structure of the cell population. AvailabilityScQcut is written in both Matlab and Python and maybe be accessed through the links below. Matlab version: cs.utsa.edu/ jruan/scQcut Python version: https://github.com/mary77/scQcut ContactJianhua.ruan@utsa.edu

bioinformatics↗

bioRxiv2021

Precise annotation of Drosophila mitochondrial genomes leads to insights into AT-rich regions

In the present study, we performed precise annotation of Drosophila melanogaster, D. simulans, D. grimshawi, Bactrocera oleae mitochondrial (mt) genomes by pan RNA-seq analysis. Our new annotations corrected or modified some of the previous annotations and two important findings were reported for the first time, including the discovery of the conserved polyA(+) and polyA(-) motifs in the control regions (CRs) of insect mt genomes and the adding of CCAs to the 3 ends of two antisense tRNAs in D. melanogaster mt genome. Using PacBio cDNA-seq data from D. simulans, we precisely annotated the Transcription Initiation Sites (TISs) of the mt Heavy and Light strands in Drosophila mt genomes and reported that the polyA(+) and polyA(-) motifs in the CRs are associated with TISs. The discovery of the conserved polyA(+) and polyA(-) motifs provides insights into many polyA and polyT sequences in CRs of insect mt genomes, leading to reveal the mt transcription and its regulation in invertebrates. In addition, we provided a high-quality, well-curated and precisely annotated D. simulans mt genome (GenBank: MN611461), which should be included into the NCBI RefSeq database to replace the current reference genome NC_005781.

bioinformatics↗

bioRxiv2021

The First High-Quality Reference Genome of Sika Deer Provides Insights for High-Tannin Adaptation

Sika deer are known to prefer oak leaves, which are rich in tannins and toxic to most mammals; however, the genetic mechanisms underlying their unique ability to adapt to living in the jungle are still unclear. In identifying the mechanism responsible for the tolerance of a highly toxic diet, we have made a major advancement in the elucidation of the genomics of sika deer. We generated the first high-quality, chromosome-level genome assembly of sika deer and measured the correlation between tannin intake and RNA expression in 15 tissues through 180 experiments. Comparative genome analyses showed that the UGT and CYP gene families are functionally involved in the adaptation of sika deer to high-tannin food, especially the expansion of UGT genes in a subfamily. The first chromosome-level assembly and genetic characterization of the tolerance toa highly toxic diet suggest that the sika deer genome will serve as an essential resource for understanding evolutionary events and tannin adaptation. Our study provides a paradigm of comparative expressive genomics that can be applied to the study of unique biological features in non-model animals.

genomics↗

bioRxiv2021

Full-length Genome of the Ogataea polymorpha strain HU-11 reveals large duplicated segments in subtelomeic regions

BackgroundCurrently, methylotrophic yeasts (e.g., Pichia pastoris, Ogataea polymorpha, and Candida boindii) are subjects of intense genomics studies in basic research and industrial applications. In the genus Ogataea, most research is focused on three basic O. polymorpha strains--CBS4732, NCYC495, and DL-1. However, the relationship between CBS4732, NCYC495, and DL-1 remains unclear, as the genomic differences between them have not be exactly determined without their high-quality complete genomes. As a nutritionally deficient mutant derived from CBS4732, the O. polymorpha strain CBS4732 ura3{Delta} (named HU-11) is being used for high-yield production of several important proteins or peptides. HU-11 has the same reference genome as CBS4732 (noted as HU-11/CBS4732), because the only genomic difference between them is a 5-bp insertion. ResultsIn the present study, we have assembled the full-length genome of O. polymorpha HU-11/CBS4732 using high-depth PacBio and Illumina data. Long terminal repeat (LTR) retrotransposons, rDNA, 5 and 3 telomeric, subtelomeric, low complexity and other repeat regions were curated to improve the genome quality. Particularly, we detected large duplicated segments (LDSs) in the subtelomeric regions and exactly determined all the structural variations (SVs) between CBS4732 and NCYC495. New findings mainly include(1) the genomic differences between HU-11/CBS4732 and NCYC495 include single nucleotide polymorphisms, small insertions and deletions, and only three SVs; (2) six genes were incorporated into CBS4732 from Cyberlindnera jadinii by horizontal gene transfer and may bring HU-11/CBS4732 new biological functions or physiological properties; (3) many recombination events may have occurred on chromosome 4 and 5 of CBS4732 and NCYC495 ancestors and two large segments were acquired by CBS4732 and NCYC495 from chromosome 6 and C. jadinii during recombination, respectively; and (4) the genome expansion in methylotrophic yeasts is mainly driven by large segment duplication in subtelomeric regions. ConclusionsThe present study preliminarily revealed the complex relationship between CBS4732, NCYC495, and DL-1. The new findings provide new opportunities for in-depth understanding of genome evolution in methylotrophic yeasts and lay the foundations for the industrial applications of O. polymorpha CBS4732, NCYC495, DL-1, and their derivative strains. The full-length genome of the O. polymorpha strain HU-11/CBS4732 should be included into the NCBI RefSeq database for future studies of Ogataea spp..

bioinformatics↗