Biology subjects

Yan, Y.

Publications and source records attributed to Yan, Y..

At least 199 records · Page 11Linked to original sources

bioRxiv2022

OligoArchive-DSM: Columnar Design for Error-Tolerant Database Archival using Synthetic DNA

The surge in demand for cost-effective, durable long-term archival media, coupled with density limitations of contemporary magnetic media, has resulted in synthetic DNA emerging as a promising new alternative. Today, the limiting factor for DNA-based data archival is the cost of writing (synthesis) and reading (sequencing) DNA. Newer techniques that reduce the cost often do so at the expense of reliability, as they introduce complex, technology-specific error patterns. In order to deal with such errors, it is important to design efficient pipelines that can carefully use redundancy to mask errors without amplifying overall cost. In this paper, we present OligoArchive-DSM (OA-DSM), an end-to-end DNA archival pipeline that can provide error-tolerant data storage at low read/write costs. Central to OA-DSM is a database-inspired columnar encoding technique that makes it possible to improve efficiency by enabling integrated decoding and consensus calling during data restoration.

bioengineering↗

bioRxiv2022

MicroRNA-335-5p suppresses voltage-gated sodium channel expression and may be a target for seizure control

There remains an urgent need for new therapies for drug-resistant epilepsy (DRE). Sodium channel blockers are effective for seizure control in common forms of epilepsy, but loss of sodium channel function underlies some genetic forms of epilepsy. Approaches that provide bi-directional control of sodium channel expression are needed. MicroRNAs (miRNA) are small non-coding RNAs which negatively regulate gene expression. Here, we show that genome-wide miRNA screening of hippocampal tissue from a rat epilepsy model, mice treated with the novel anti-seizure medicine cannabidiol (CBD) and plasma from patients with DRE, converge on a single target, miR-335-5p. Pathway analysis on predicted and validated miR-335-5p targets identified multiple voltage-gated sodium channels (VGSCs). Intracerebroventricular injection of antisense oligonucleotides against miR-335-5p resulted in upregulation of Scn1a, Scn2a and Scn3a in the mouse brain and an increased action potential rising phase and greater excitability of hippocampal pyramidal neurons in brain slice recordings, consistent with VGSCs as functional targets of miR-335-5p. Blocking of miR-335-5p also increased voltage-gated sodium currents in human iPSC-derived neurons. Inhibition of miR-335-5p increased susceptibility to tonic-clonic seizures in the pentylenetetrazole seizure model, whereas AAV9-mediated overexpression of miR-335-5p reduced seizure severity and improved survival. These studies suggest modulation of miR-335-5p may be a means to regulate VGSCs and affect brain excitability and seizures. Changes to miR-335-5p may reflect compensatory mechanisms to control excitability and could provide new biomarker or therapeutic strategies for different types of drug-resistant epilepsy. Significance StatementDespite the clinical availability of over 30 anti-seizure medications (ASMs), around 30% of people with epilepsy do not achieve seizure freedom. MicroRNAs are small non-coding RNAs which negatively regulate protein expression by binding to target mRNAs. Here, we identified the brain-enriched miR-335-5p to be commonly altered in three heterogenous miRNA profiling datasets. Bi-directional modulation of miR-335-5p identified a potential homeostatic role of miR-335-5p in brain excitability involving voltage-gated sodium channels. Electrophysiological and in vivo approaches revealed pro-epileptic activity of miR-335-5p inhibition whereas overexpression of miR-335-5p resulted in anti-epileptic activity. Overall, targeting miR-335-5p could provide a new approach in the modulation of brain excitability, with possible therapeutic applications in drug-resistant epilepsies and other neurological diseases.

neuroscience↗

bioRxiv2022

Chaperones Hsc70 and Hsp70 Play Distinct Roles in Bocaparvovirus Minute Virus of Canines Infection

Minute virus of canines (MVC) belongs to the genus Bocaparvovirus and reproduces rapidly in its permissive cells Walter Reed/3873D (WRD). The crosstalk between MVC and WRD is poorly characterized in terms of molecular requirements and mechanisms. Here, we identified two novel cellular proteins Hsc70 and Hsp70 that interact with both NS1 and VP2 via mass spectrometry (MS), co-immunoprecipitation (Co-IP) and confocal immunofluorescence assays (IFA). Hsp70 was upregulated upon MVC infection. Respective silencing of Hsc70 and Hsp70 led to contrasting results at nearly every stage of MVC life cycle, including virus entry, transcription, translation, replication and production. Strikingly, transfection with low and high dose of pFlag-Hsp70 contributed to opposing impacts on viral protein levels and virus production possibly through a ubiquitin-dependent manner, indicating that MVC is quite sensitive to the levels of Hsp70. Treatment with quercetin and VER155008, two Hsp70 family inhibitors, both significantly decreased viral replication and particle levels. Together, these results illustrated that both Hsc70 and Hsp70 are involved in MVC life cycle, and targeting to Hsp70 family may represent a novel anti-MVC mechanism.

molecular biology↗

bioRxiv2022

Genetically encoded sensors for measuring histamine release both in vitro and in vivo

Histamine (HA) is a key biogenic monoamine involved in a wide range of physiological and pathological processes in both the central nervous system and the periphery. Because the ability to directly measure extracellular HA in real-time will provide important insights into the functional role of HA in complex circuits under a variety of conditions, we developed a series of genetically encoded G protein-coupled receptor activation-based (GRAB) HA (GRABHA) sensors. These sensors produce a robust increase in fluorescence upon HA application, with good photostability, sub-second kinetics, nanomolar affinity, and high specificity. Using these GRABHA sensors, we measured electrical stimulation-evoked HA release in acute brain slices with high spatiotemporal resolution. Moreover, we recorded HA release in the preoptic area of the hypothalamus and in the medial prefrontal cortex during the sleep-wake cycle in freely moving mice, finding distinct patterns of HA release in these specific brain regions. Together, these in vitro and in vivo results show that our GRABHA sensors have high sensitivity and specificity for measuring extracellular HA, thus providing a robust new set of tools for examining the role of HA signaling in both health and disease.

neuroscience↗

bioRxiv2022

Testis-specific H2BFWT disrupts nucleosome integrity through reductions of DNA-histone interactions

During spermatogenesis, multiple testis-specific histone variants are involved in the dynamic chromatin transitions. H2BFWT is a primate testis-specific H2B variant with hitherto unclear functions, and SNPs of H2BFWT are closely associated with male non-obstructive infertility. Here, we found that H2BFWT is preferentially localized in the sub-telomeric regions and the promoters of genes highly expressed in testis from differentiated spermatogonia to early spermatocytes. Cryo-EM structural analysis shows that H2BFWT nucleosomes are defined by weakened interactions between H2A-H2BFWT dimer and H4, and between histone octamer and DNA. Furthermore, one of its SNPs, H2BFWTH100R further destabilizes nucleosomes and increases the nucleosome unwrapping rate by interfering with the interaction with H4K91. Our results suggest that H2BFWT may be necessary for the regulation of spermatogenesis-related gene expression by decreasing transcriptional barriers, and that H2BFWTH100R overdrives its nucleosome-destabilizing effects which causes infertility.

biochemistry↗

bioRxiv2022

Network predictions sharpen the representation of visual features for categorization

Models of visual cognition assume that brain networks predict the contents of a stimulus to facilitate its subsequent categorization. However, the specific network mechanisms of this facilitation remain unclear. Here, we studied them in 11 individual participants cued to the spatial location (left vs. right) and contents (Low vs. High Spatial Frequency, LSF vs. HSF) of an upcoming Gabor stimulus that they categorized. Using concurrent MEG recordings, we reconstructed in each participant the network that communicates the predicted contents and the network that represents these contents from the stimulus for categorization. We show that predictions of LSF vs. HSF propagate top-down from temporal to contra-lateral occipital cortex, with modulatory supervision from frontal cortex. In occipital cortex, predictions sharpen bottom-up stimulus LSF vs. HSF representations, leading to faster categorizations. Our results therefore reveal functional networks that predict visual contents to sharpen their representations from the stimulus to facilitate categorization behavior.

neuroscience↗

bioRxiv2022

On-target inhibition of Cryptosporidium parvum by nitazoxanide (NTZ) and paclitaxel (PTX) validated using a novel MDR1-transgenic host cell model and algorithms to quantify on/off-target rates

Cryptosporidium parvum is a globally distributed zoonotic protozoan parasite that causes moderate to severe, sometime deadly, watery diarrhea in humans and animals, for which fully effective treatments are yet unavailable. In the study of mechanism of action of drugs against intracellular pathogens, it is important to validate whether the observed anti-infective activity is attributed to the drug action on the pathogen (on-target effect) or host cells (off-target effect). For the epicellular Cryptosporidium, we have previously developed a concept that the host cells with significantly increased drug tolerance by transient overexpression of the multidrug resistance protein-1 (MDR1) could be utilized to evaluate whether an observed anti-cryptosporidial activity of an inhibitor was attributed to the action of the inhibitor on the parasite or host cell targets. However, the transient transfection model was only applicable to evaluating inhibitors that were MDR1 substrates. Here we report an advanced model using stable MDR1-transgenic HCT-8 cells that allowed continuous application of drug pressure for rapid development of novel resistance to non-MDR1 substrates. Using the new model, we successfully validated that nitazoxanide, the only FDA-approved drug to treat human cryptosporidiosis and non-MDR1 substrate, killed C. parvum by fully acting on the parasite target (100% on-target). We also confirmed that paclitaxel acted fully on-target, while several other inhibitors including mitoxantrone, doxorubicin, vincristine and ivermectin acted partially on-target. Additionally, we developed mathematical models to quantify the proportional contributions of on-target and off-target effects to the observed anti-cryptosporidial activity and to evaluate the relationships between antiparasitic efficacy (ECi), cytotoxicity (TCi), safety interval (SI) and Hill slope (h) parameters. Owning to the promiscuity of the MDR1 efflux pump, the MDR1-transgenic host cell model could be applied to assess the on/off-target effects of newly hits/leads, either substrates or non-substrates of MDR1, against Cryptosporidium or other epicellular pathogens. Author SummaryCryptosporidium parvum is an important zoonotic parasite, for which fully effective treatments are unavailable. Anti-cryptosporidial drug discovery faces many challenges and technical difficulties. One obstacle is the lack of tools to assess whether the killing of C. parvum by an inhibitor is attributed to the action of the inhibitor on the parasite or on host cells. To address this question, we developed an MDR1-transgenic host cell line that allowed rapid development of drug resistance by applying continuous drug pressure. By analyzing the antiparasitic activity and cytotoxicity between wild-type and drug-resistant host cells, we verified that nitazoxanide (the only FDA-approved drug for treating cryptosporidiosis) and paclitaxel (anti-cryptosporidial lead) killed the parasite by acting fully on the parasite, whereas mitoxantrone, doxorubicin, vincristine and ivermectin killed the parasite by acting on both the parasite and host cells. We also developed algorithms to quantify the percent contributions of actions on the parasite and host cells to the observed anti-cryptosporidial activity. In summary, we developed novel in vitro and mathematical models for evaluating/quantifying the on/off-target effects of anti-cryptosporidial drugs. The models are also applicable to evaluate/quantify the drug actions on other epicellular pathogens.

microbiology↗

bioRxiv2022

Chemical genetic screening identifies nalacin as an inhibitor of GH3 amido synthetase for auxin conjugation

Root system is critical for plant growth and development. To develop plant growth regulators functioning in root development, we performed a phenotype-based chemical screen in Arabidopsis and identified a chemical, nalacin, that mimicked the effects of auxin on root development. Genetic, pharmacological and biochemical approaches demonstrated that nalacin exerts its auxin-like activities by inhibiting indole-3-acetic acid (IAA) conjugation that is mediated by Gretchen Hagen 3 (GH3) acyl acid amido synthetases. The crystal structure of Arabidopsis GH3.6 in complex with D4 (a derivative of nalacin) together with docking simulation analysis revealed the molecular basis of the inhibition of group II GH3 by nalacin. Sequence alignment analysis indicated broad bioactivities of nalacin and D4 as inhibitors of GH3s in vascular plants, which were confirmed, at least, in tomato and rice. In summary, our work identifies nalacin as a potent inhibitor of IAA conjugation mediated by group II GH3 that plays versatile roles in hormone-regulated plant development and has potential applications in both basic research and agriculture.

plant biology↗

bioRxiv2022

A bacterial E2 enzyme regulates an antiviral cGAS through a peptide exchange-ligation-cleavage mechanism

The cyclic oligonucleotide-based anti-phage signaling system (CBASS) is a family of defense system in prokaryotes1, 2. Composed of a cyclic GMP-AMP synthase (cGAS) and CBASS-associated proteins, CBASS utilizes cyclic oligonucleotides to activate antiviral immunity3-6. One major group of CBASS-associated proteins are homologs of eukaryotic E2 ubiquitin-conjugating enzymes. However, the function of E2 in CBASS remains elusive. Here, we report that a bacterial E2 enzyme regulates cGAS by imitating the entire ubiquitination cascade. This includes the processing of the cGAS C-terminus, conjugation of cGAS to a cysteine residue, ligation of cGAS to a lysine residue, cleavage of the isopeptide bond, and poly-cGASylation. The poly-cGASylation fully activates cGAS to produce cGAMP, which acts as an antiviral signal and leads to cell death. Our findings reveal unique regulatory roles of E2 in CBASS and provide insights into the origin of the ubiquitin system.

microbiology↗

bioRxiv2022

The Structural and Biochemical Basis for FER Receptor Kinase Early Signaling Initiation in Arabidopsis

Accumulating evidence has indicated that receptor-like kinase (RLK) autophosphorylation and substrate phosphorylation triggered by RLK are early and essential events for RLK function. However, the structural and biochemical basis for these early events is largely unclear. Herein, we used RLK FERONIA (FER) as a model and crystallized its core kinase domain (FER-KD) in the dephosphorylated state. We found that FER-KD adopts an active conformation in its crystal structure. Moreover, FER-KD mutants with reduced or no catalytic activity also adopt an active conformation before phosphorylation. Collectively, these observations suggest that FER employs a phosphorylation-independent active state before ligand-induced phosphorylation and full activation. We further demonstrated that FER is a dual-specificity kinase and that autophosphorylation on Tyr residues lags somewhat behind Ser/Thr phosphorylation. More importantly, Tyr phosphorylation is essential for FER-KD to initiate substrate GRP7 phosphorylation. Our work provides a paradigm to study the mechanisms of the early steps of RLK signaling initiation and highlights its "active" form and Tyr phosphorylation-gated roles in response to signaling stimuli.

biochemistry↗

bioRxiv2022

A toolkit of highly selective and sensitive genetically encoded neuropeptide sensors

Neuropeptides are key signaling molecules in the endocrine and nervous systems that regulate many critical physiological processes, including energy balance, sleep and circadian rhythms, stress, and social behaviors. Understanding the functions of neuropeptides in vivo requires the ability to monitor their dynamics with high specificity, sensitivity, and spatiotemporal resolution; however, this has been hindered by the lack of direct, sensitive and non-invasive tools. Here, we developed a series of GRAB (G protein-coupled receptor activation-based) sensors for detecting somatostatin (SST), cholecystokinin (CCK), corticotropin-releasing factor (CRF), neuropeptide Y (NPY), neurotensin (NTS), and vasoactive intestinal peptide (VIP). These fluorescent sensors utilize the corresponding GPCRs as the neuropeptide-sensing module with the insertion of a circular-permutated GFP as the optical reporter. This design detects the binding of specific neuropeptides at nanomolar concentration with a robust increase in fluorescence. We used these GRAB neuropeptide sensors to measure the spatiotemporal dynamics of endogenous SST release in isolated pancreatic islets and to detect the release of both CCK and CRF in acute brain slices. Moreover, we detect endogenous CRF release induced by stressful experiences in vivo using fiber photometry and 2-photon imaging in mice. Together, these new sensors establish a robust toolkit for studying the release, function, and regulation of neuropeptides under both physiological and pathophysiological conditions.

neuroscience↗

bioRxiv2022

Allele-specific activation, enzyme kinetics, and inhibitor sensitivities of EGFR exon 19 deletion mutations in lung cancer

Oncogenic mutations within the epidermal growth factor receptor (EGFR) are found in 15-30% of all non-small cell lung carcinomas. The term exon 19 deletion (ex19del) is collectively used to refer to more than 20 distinct genomic alterations within exon 19 that comprise the most common EGFR mutation subtype in lung cancer. Despite this heterogeneity, clinical treatment decisions are made irrespective of which EGFR ex19del variant is present within the tumor, and there is a paucity of information regarding how individual ex19del variants influence protein structure and function. Herein, we identify allele-specific functional differences among ex19del variants attributable to recurring sequence and structure motifs. We build all-atom structural models of 60 ex19del variants identified in patients and combine ~400 s of molecular dynamics simulations with biochemical and biophysical experiments to analyze three ex19del mutations (E746_A750, E746_S752>V, and L747_A750>P). We demonstrate that sequence variation in ex19del alters oncogenic cell growth, dimerization propensity, and tyrosine kinase inhibitor (TKI) sensitivity. We show that in contrast to E746_A750 and E746_S752>V, the L747_A750>P variant forms highly active ligand-independent dimers. E746_S752>V displays the least TKI sensitivity among the variants tested, which enzyme kinetic analysis and TKI inhibition experiments suggest is due to increased ATP Km relative to the common E746_A750 variant. Through these analyses, we propose an expanded framework for interpreting ex19del variants and new considerations for therapeutic intervention. SignificanceEGFR mutations are detected in approximately 30% of all lung adenocarcinomas, and the most common EGFR mutation occurring in ~50% of patients is termed "exon 19 deletion" (ex19del). Despite the existence of dozens of different genomic variants comprising what is generically referred to clinically as ex19del, clinicians currently do not distinguish between ex19del variants in considering treatment options, and the differences between ex19del variants are largely unstudied in the broader scientific community. Herein, we describe functional differences between distinct EGFR ex19del variants attributable to the structural features of each variant. These findings suggest a possible explanation for observed differences in patient outcomes stratified by ex19del subtype and reinforce the need for allele-specific considerations in clinical treatment decision making.

cancer biology↗

bioRxiv2022

Resolving clonal substructure from single cell genomic data using CopyKit

High-throughput methods for single cell copy number sequencing have enabled the profiling of thousands of cells in parallel, yet there remains a significant bottleneck for data analysis. Here we present CopyKit, a comprehensive set of computational methods for the pre-processing and analysis of single cell copy number data to resolve clonal substructure and reconstruct genetic lineages in tumors. We performed single cell DNA sequencing of 2977 cells from multiple spatial regions in two liver metastasis and 7365 cells from three primary tumors with matched metastatic tissues. In the liver metastases, CopyKit resolved clonal substructure in different spatial regions, which revealed both clonal intermixing and spatial segregation in the tumor mass. In the matched metastatic colorectal and breast cancers, CopyKit resolved metastatic lineages and identified subclones and genomic events that were associated with metastases. These applications show that CopyKit is comprehensive tool for resolving copy number substructure in tumors.

genomics↗

bioRxiv2022

Reduced Hippocampal-Cortical Connectivity During Memory Suppression Predicts the Ability to Forget Unwanted Memories

The ability to suppress unwelcome memories is important for productivity and well-being. Successful memory suppression is associated with hippocampal deactivations and a concomitant disruption of this regions functionality. Much of the previous neuroimaging literature exploring such suppression-related hippocampal modulations has focused on the regions negative coupling with the prefrontal cortex. In contrast, task-based changes in functional connectivity between the hippocampus and other brain regions have remained relatively underexplored. Here, we utilize psychophysiological interactions and seed connectome-based predictive modeling (seed-CPM) to investigate the relationship between the hippocampus and the rest of the brain as 134 participants attempted to suppress unwanted memories during the Think/No-Think task. The results show that during retrieval suppression, the right hippocampus exhibited decreased functional connectivity with visual cortical areas (bilateral intracalcarine cortex, right cuneal cortex, left lingual gyrus, right supracalcarine cortex, right occipital pole), left nucleus accumbens and the brain-stem that predicted superior forgetting of unwanted memories on later memory tests. Validation tests verified that prediction performance was not an artifact of head motion or prediction method and that the negative features remained consistent across different brain parcellations. These findings suggest that systemic memory suppression involves more than the modulation of hippocampal activity--it alters functional connectivity patterns between the hippocampus and visual cortex, leading to successful forgetting.

neuroscience↗

bioRxiv2022

Spatial and molecular anatomy of germ layers in the gastrulating primate embryo

During mammalian embryogenesis, spatial regulation of gene expression and cell signaling are functionally coupled with lineage specification, patterning of tissue progenitors and germ layer morphogenesis. While the mouse model has been instrumental for our understanding of mammalian development, comparatively little is known about human and non-human primate gastrulation due to the restriction of both technical and ethical issues. Here, we present a morphological and molecular survey of spatiotemporal dynamics of cell types populating the non-human primate embryos during gastrulation. We performed serial sections of Cynomolgus monkeys (Macaca fascicularis) gastrulating embryos at 1-day temporal resolution from E17 to E21, and reconstructed three-dimensional digital models based on high-resolution anatomical atlas that revealed the dynamic changes in the geography of the mesoderm and primitive streaks. Spatial transcriptomics identified unique gene profiles that correspond to distinct germ layers and cross-species spatiotemporal transcriptome analysis revealed a developmental coordinate of germ layer segregation between mouse and primate. Furthermore, we identified species-specific transcription programs during gastrulation. These results offer important insights into evolutionarily conserved and divergent processes during mammalian gastrulation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=196 SRC="FIGDIR/small/474719v2_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@1058f45org.highwire.dtl.DTLVardef@105cborg.highwire.dtl.DTLVardef@12362d7org.highwire.dtl.DTLVardef@2e2346_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightO_LIA high-resolution anatomical atlas of Cynomolgus gastrulation embryos C_LIO_LICreated a three-dimensional digital template from serial sections of five developmental stages C_LIO_LIA two-dimensional spatiotemporal transcriptome of the germ layers of gastrulating embryos C_LIO_LICross-species comparison infers conservation of functional attributes of regulome and signaling activity in germ layer formation C_LI

developmental biology↗

bioRxiv2022

The IMD and JNK pathways drive the functional integration of the immune and circulatory systems of mosquitoes

The immune and circulatory systems of animals are functionally integrated. In mammals, the spleen and lymph nodes filter and destroy microbes circulating in the blood and lymph, respectively. In insects, immune cells that surround the heart valves (ostia), called periostial hemocytes, destroy pathogens in the areas of the body that experience the swiftest hemolymph (blood) flow. An infection recruits additional periostial hemocytes, amplifying heart-associated immune responses. Although the structural mechanics of periostial hemocyte aggregation have been defined, the genetic factors that regulate this process remain less understood. Here, we conducted RNAseq in the African malaria mosquito, Anopheles gambiae, and discovered that an infection upregulates multiple components of the IMD and JNK pathways in the heart with periostial hemocytes. This upregulation is greater in the heart with periostial hemocytes than in the circulating hemocytes or the entire abdomen. RNAi-based knockdown then showed that the IMD and JNK pathways drive periostial hemocyte aggregation and alter phagocytosis and melanization on the heart, thereby demonstrating that these pathways regulate the functional integration between the immune and circulatory systems. Understanding how insects fight infection lays the foundation for novel strategies that could protect beneficial insects and harm detrimental ones.

immunology↗

bioRxiv2022

A new demethylase gene OsDML4 involved in high temperature induced floury endosperm formation in rice

High temperature (HT) can affect the accumulation of seed storage materials and cause adverse effects on the yield and quality in rice. DNA methylation plays an important role in plant growth and development. However, the temperature and DNA methylation interaction on rice seed development has not been studied yet. Here, we identified a new demethylase gene OsDML4 and discovered its function on cytosine demethylation to affect the endosperm formation during the grain filling. Knockout of OsDML4 induced floury endosperm only under HT, which resulted from dramatically reduced the transcription and accumulation of glutelins and 16-kDa prolamin. The expression of two important transcription factors RISBZ1 and RPBF was significantly declined in the osdml4 mutants. The absence of OsDML4 also caused adverse effects on the formation of protein bodies (PBs), the number of PB-II was greatly decreased and incomplete PB-II with empty space and abnormally shaped PB-II were observed in the osdml4 mutants. Whole-genome bisulfite sequencing analysis of seeds at 15 days after pollination revealed much higher global methylation levels of CG, CHG and CHH contexts in the osdml4 mutants compared to wild type (WT). Moreover, the methylation status of RISBZ1 promoter was hypermethylated but RPBF promoter was nearly unchanged. No significant difference was detected between WT and the osdml4 mutants under room temperature. In conclusion, our study demonstrates a novel OsDML4-mediated epigenetic regulatory mechanism involving in the formation of floury endosperm, which will provide a new perspective in regulating endosperm development and the accumulation of SSPs in rice.

plant biology↗

bioRxiv2022

SELINA: Single-cell Assignment using Multiple-Adversarial Domain Adaptation Network with Large-scale References

The rapid accumulation of single-cell RNA-seq data has provided rich resources to characterize various human cell types. Cell type annotation is the critical step in analyzing single-cell RNA-seq data. However, accurate cell type annotation based on public references is challenging due to the inconsistent annotations, batch effects, and poor characterization of rare cell types. Here, we introduce SELINA (single cELl identity NAvigator), an integrative annotation transferring framework for automatic cell type annotation. SELINA optimizes the annotation for minority cell types by synthetic minority over-sampling, removes batch effects among reference datasets using a multiple-adversarial domain adaptation network (MADA), and fits the query data with reference data using an autoencoder. Finally, SELINA affords a comprehensive and uniform reference atlas with 1.7 million cells covering 230 major human cell types. We demonstrated the robustness and superiority of SELINA in most human tissues compared to existing methods. SELINA provided a one-stop solution for human single-cell RNA-seq data annotation with the potential to extend for other species.

bioinformatics↗