Biology subjects

Liu, Y.

Publications and source records attributed to Liu, Y..

At least 1,477 records · Page 82Linked to original sources

bioRxiv2023

DBT is a metabolic switch for maintenance of proteostasis under proteasomal impairment

Proteotoxic stress impairs cellular homeostasis and underlies the pathogenesis of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). The proteasomal and autophagic degradation of proteins are two major pathways for protein quality control in the cell. Here, we report a genome-wide CRISPR screen uncovering a major regulator of cytotoxicity resulting from the inhibition of the proteasome. Dihydrolipoamide branched chain transacylase E2 (DBT) was found to be a robust suppressor, the loss of which protects against proteasome inhibition-associated cell death through promoting clearance of ubiquitinated proteins. Loss of DBT altered the metabolic and energetic status of the cell and resulted in activation of autophagy in an AMP-activated protein kinase (AMPK)-dependent mechanism in the presence of proteasomal inhibition. Loss of DBT protected against proteotoxicity induced by ALS-linked mutant TDP-43 in Drosophila and mammalian neurons. DBT is upregulated in the tissues from ALS patients. These results demonstrate that DBT is a master switch in the metabolic control of protein quality control with implications in neurodegenerative diseases.

neuroscience↗

bioRxiv2023

Functional connectome through the human life span

The lifespan growth of the functional connectome remains unknown. Here, we assemble task-free functional and structural magnetic resonance imaging data from 33,250 individuals aged 32 postmenstrual weeks to 80 years from 132 global sites. We report critical inflection points in the nonlinear growth curves of the global mean and variance of the connectome, peaking in the late fourth and late third decades of life, respectively. After constructing a fine-grained, lifespan-wide suite of system-level brain atlases, we show distinct maturation timelines for functional segregation within different systems. Lifespan growth of regional connectivity is organized along a primary-to-association cortical axis. These connectome-based normative models reveal substantial individual heterogeneities in functional brain networks in patients with autism spectrum disorder, major depressive disorder, and Alzheimers disease. These findings elucidate the lifespan evolution of the functional connectome and can serve as a normative reference for quantifying individual variation in development, aging, and neuropsychiatric disorders.

neuroscience↗

bioRxiv2023

Bet hedging in a unicellular microalga

AbstractUnderstanding how organisms adapt to unpredictable future environments is a fundamental goal in biology, which becomes even more urgent in an era of rapid climate change. One evolutionary adaptation to randomly fluctuating environments is bet hedging, a strategy that successfully facilitates reproduction and population persistence and has been widely reported from microbes to humans. Empirical evidence for its presence in microalga, one of Earths most important primary producers and carbon sinks, is lacking. Here, we report a bet-hedging strategy in the unicellular microalga Haematococcus pluvialis. In a series of experiments, we show that an isogenic H. pluvialis population reversibly diversifies into hetero-phenotypic mobile and non-mobile subunits, independent of environmental conditions. Mobile cells grow faster but are more susceptible to external stressors, while non-mobile cells hardly grow but are more stress-resistant. This is attributed to dramatic shifts from growth-promoting activities (cell division, photosynthesis) to resilience-promoting cellular metabolic processes, including cell enlargement and aggregation, and accumulation of antioxidant and energy-storaging compounds. Our results provide experimental evidence for bet hedging in microalga, which has implications for their potential to adapt to current and predicted future conditions, and thus for the conservation of ecosystem functions.

ecology↗

bioRxiv2023

Structural basis for EROS binding to human phagocyte NADPH oxidase NOX2

EROS (essential for reactive oxygen species) is a recently identified molecular chaperone of NOX2 (gp91phox), the catalytic subunit of phagocyte NADPH oxidase. Deficiency in NOX2 expression or function due to genetic mutations leads to chronic granulomatous disease (CGD) with recurrent bacterial and fungal infections. To delineate how EROS interacts with NOX2, we solved the cryo-EM structure of the EROS-NOX2-p22phox heterotrimeric complex. EROS binds to NOX2 in plasma membrane through its anti-parallel -helices H1 and H2, and in cytoplasm through multiple {beta}-strands that form hydrogen bonds with the C terminal fragment of NOX2. EROS binding alters the conformation of the TM2 and TM6 transmembrane helices, increases the distance between the two hemes, and causes dislocation of the binding site for flavin adenine dinucleotide (FAD). EROS colocalizes with NOX2 on cell surface of neutrophil-like HL-60 cells and forms a heterotrimer with mature NOX2-p22phox in transfected cells. Phorbol myristate acetate, an activator of NOX2, induces dissociation of EROS from NOX2 in a NanoLuc complementation assay with concurrent production of superoxide in reconstituted cells. Taken together, these findings provide a structural basis for EROS-NOX2 interaction and suggest a previously unidentified function of EROS in regulating NOX2 activation.

immunology↗

bioRxiv2023

Pan-cancer characterization and clinical outcome of ecDNA-enhancer mediated transcriptional dysregulation

Extrachromosomal circular DNAs (ecDNAs) are extrachromosomal circular DNA elements harboring enhancers that can function as mobile transcriptional enhancers to promote oncogene amplification in diverse human cancers. However, little is known about the mechanism how ecDNA and relevant enhancers influence the transcription control in different cancers. Here, we performed a comprehensive pan-cancer analysis to explore the potential transcriptional regulatory network between ecDNA and enhancer, and the association with clinical outcomes in different human cancers. Firstly, we identified 18,385 enhancers on ecDNA in 1,921 samples of 20 TCGA tumors. By integrating corresponding RNA-seq data, we found that the expression levels of enhancer RNAs (eRNAs) were significantly different between ecDNA regions and corresponding linear chromosomes. This suggested that enhancers on ecDNA may employ eRNA to perform transcriptional regulation. Furthermore, we identified enhancer co-amplification with oncogenes and found that enhancers on ecDNA significantly affect the expression of co-amplified cancer genes and consequently influence the survival of cancer patients. In addition, we found that, compared to corresponding linear chromosomes, enhancers on ecDNA generally have lower levels of methylation, which may be mainly caused by the enhancer co-amplification with oncogenes. Genome-wide analysis of open chromatin regions revealed significantly higher levels of chromatin accessibility and certain chromosomal preferences in ecDNA regions comparing corresponding linear chromosomes. Moreover, we found that the downregulation of antigen presentation genes and the suppression of antigen presentation pathways may cause the tumor immune evasion mediated by ecDNA. Finally, we identified tumor-infiltrating activated mast cells in ecDNA-positive patients, which are associated with poorer prognosis. In summary, through pan-cancer analysis, we illustrate the characteristics and regulatory mechanisms of ecDNA and its enhancers in cancers, providing insights for future cancer treatment.

bioinformatics↗

bioRxiv2023

Exposure-based sequence learning induces backward replay in the human visual cortex

The ability of cortical circuits to adapt in response to experience is a fundamental property of the brain. After exposure to a moving dot sequence, flashing a dot as a cue at the starting point of the sequence can elicit successive elevated responses even in the absence of the sequence. These cue-triggered elevated responses have been shown to play a crucial role in predicting future events in dynamic environments. However, temporal sequences we are exposed typically contain rich feature information. It remains unknown whether the elevated responses are feature specific and, more crucially, how the brain organizes sequence information after exposure. To address these questions, participants were exposed to a predefined sequence of four motion directions for about 30 min, followed by the presentation of the start or end motion direction of the sequence as a cue. Surprisingly, we found that cue-triggered elevated responses were not specific to any motion direction. Interestingly, motion direction information was spontaneously reactivated, and the motion sequence was backward replayed in a time-compressed manner. These effects were observed even after brief exposure. Notably, no replay events were observed when the second or third motion direction of the sequence served as a cue. Further analyses revealed that activity in the medial temporal lobe (MTL) preceded the ripple power increase in visual cortex at the onset of replay, implying a coordinated relationship between the activities in the MTL and visual cortex. Together, these findings demonstrate that visual sequence exposure induces two-fold brain plasticity that may simultaneously serve for different functional purposes. The non-feature-specific elevated responses may facilitate general processing of upcoming stimuli, whereas the feature-specific backward replay may underpin passive learning of visual sequence.

neuroscience↗

bioRxiv2023

DropBlot: single-cell western blotting of chemically fixed cancer cells

To further realize proteomics of archived tissues for translational research, we introduce a hybrid microfluidic platform for high-specificity, high-sensitivity protein detection from individual chemically fixed cells. To streamline processing-to-analysis workflows and minimize signal loss, DropBlot serially integrates sample preparation using droplet-based antigen retrieval from single fixed cells with unified analysis-on-a-chip comprising microwell-based antigen extraction followed by chip-based single-cell western blotting. A water-in-oil droplet formulation proves robust to the harsh chemical (SDS, 6M urea) and thermal conditions (98{degrees}C, 1-2 hr.) required for sufficient antigen retrieval, and the electromechanical conditions required for electrotransfer of retrieved antigen from microwell-encapsulated droplets to single-cell electrophoresis. Protein-target retrieval was demonstrated for unfixed, paraformaldehyde-(PFA), and methanol-fixed cells. We observed higher protein electrophoresis separation resolution from PFA-fixed cells with sufficient immunoreactivity confirmed for key targets (HER2, GAPDH, EpCAM, Vimentin) from both fixation chemistries. Multiple forms of EpCAM and Vimentin were detected, a hallmark strength of western-blot analysis. DropBlot of PFA-fixed human-derived breast tumor specimens (n = 5) showed antigen retrieval from cells archived frozen for 6 yrs. DropBlot could provide a precision integrated workflow for single-cell resolution protein-biomarker mining of precious biospecimen repositories.

bioengineering↗

bioRxiv2023

Tauopathy severely disrupts homeostatic set-points in emergent neural dynamics but not the activity of individual neurons.

The homeostatic regulation of neuronal activity is essential for robust computation; key set-points, such as firing rate, are actively stabilized to compensate for perturbations. From this perspective, the disruption of brain function central to neurodegenerative disease should reflect impairments of computationally essential set-points. Despite connecting neurodegeneration to functional outcomes, the impact of disease on set-points in neuronal activity is unknown. Here we present a comprehensive, theory-driven investigation of the effects of tau-mediated neurodegeneration on homeostatic set-points in neuronal activity. In a mouse model of tauopathy, we examine 27,000 hours of hippocampal recordings during free behavior throughout disease progression. Contrary to our initial hypothesis that tauopathy would impact set-points in spike rate and variance, we found that cell-level set-points are resilient to even the latest stages of disease. Instead, we find that tauopathy disrupts neuronal activity at the network-level, which we quantify using both pairwise measures of neuron interactions as well as measurement of the networks nearness to criticality, an ideal computational regime that is known to be a homeostatic set-point. We find that shifts in network criticality 1) track with symptoms, 2) predict underlying anatomical and molecular pathology, 3) occur in a sleep/wake dependent manner, and 4) can be used to reliably classify an animals genotype. Our data suggest that the critical set-point is intact, but that homeostatic machinery is progressively incapable of stabilizing hippocampal networks, particularly during waking. This work illustrates how neurodegenerative processes can impact the computational capacity of neurobiological systems, and suggest an important connection between molecular pathology, circuit function, and animal behavior.

neuroscience↗

bioRxiv2023

Approximate Bayesian Computation for Inferring Waddington Landscapes from Single Cell Data

Single cell technologies allow us to gain insights into cellular processes at unprecedented resolution. In stem cell and developmental biology snapshot data allows us to characterise how the transcriptional state of cells changes between successive cell types. Here we show how approximate Bayesian computation (ABC) can be employed to calibrate mathematical models against single cell data. In our simulation study we demonstrate the pivotal role of the adequate choice of distance measures appropriate for single cell data. We show that for good distance measures, notably optimal transport distances, we can infer parameters for mathematical models from simulated single cell data. We show that the ABC posteriors can be used to characterise parameter sensitivity and identify dependencies between different parameters, and to infer representations of the Waddington or epigenetic landscape, which forms a popular and interpretable representation of the developmental dynamics. In summary, these results pave the way for fitting mechanistic models of stem cell differentiation to single cell data.

systems biology↗

bioRxiv2023

Melanin-concentrating hormone receptor antagonism differentially attenuates nicotine experience-dependent locomotor behavior in female and male rats

Nicotine is a significant public health concern because it is the primary pharmacological agent in tobacco use disorder. One neural system that has been implicated in the symptoms of several substance use disorders is the melanin-concentrating hormone (MCH) system. MCH regulates various motivated behaviors depending on sex, yet little is known of how this interaction affects experience with drugs of abuse, particularly nicotine. The goal of this study was to determine the effect of MCH receptor antagonism on experience-dependent nicotine-induced locomotion after chronic exposure, particularly on the expression of locomotor sensitization. Adult female and male Wistar rats were given saline then cumulative doses of nicotine (0.1, 0.32, 0.56, and 1.0 mg/kg) intraperitoneally to determine the acute effects of nicotine (day 1). Next, rats were treated with 1.0 mg/kg nicotine for 6 days, given an identical series of cumulative doses (day 8), and then kept in a drug-free state for 6 days. On day 15, rats were pretreated with vehicle or the MCH receptor antagonist GW803430 (10 or 30 mg/kg) before another series of cumulative doses to assess response to chronic nicotine. After vehicle, male rats increased nicotine locomotor activation from day 1 to day 15, and both sexes showed a sensitized response when normalized to saline. The lower dose of GW803430 decreased locomotion compared to vehicle in females, while the higher dose decreased locomotion in males. Both sexes showed nicotine dose-dependent effects of GW803430, strongest at lower doses of nicotine. Controlling for sex-based locomotor differences revealed that females are more sensitive to GW803430. The high dose of GW803430 also decreased saline locomotion in males. Together, the results of our study suggest that MCH is involved in the expression of nicotine locomotor sensitization, and that MCH regulates these nicotine behavioral symptoms differently across sex.

pharmacology and toxicology↗

bioRxiv2023

Inhibition of CREB binding and function with a dual-targeting ligand

CBP/p300 is a master transcriptional coactivator, regulating gene activation by interacting with multiple transcriptional activators. Dysregulation of protein-protein interactions (PPIs) between the CBP/p300 KIX domain and its activators is implicated in a number of cancers including breast, leukemia, and colorectal cancer. However, KIX is typically considered undruggable because of its shallow binding surfaces lacking both significant topology and promiscuous binding profiles. We previously reported a dual-targeting peptide (MybLL-tide) that inhibits the KIX-Myb interaction with excellent specificity and potency. Here we demonstrate a branched, second-generation analog, CREBLL-tide, that inhibits the KIX-CREB PPI with higher potency and selectivity. Additionally, the best of these CREBLL-tide analogs shows excellent and selective anti-proliferation activity in breast cancer cells. These results indicate CREBLL-tide is an effective tool for assessing the role of KIX-activator interactions in breast cancer and expanding the dual-targeting strategy for inhibiting KIX and other coactivators that contain multiple binding surfaces.

biochemistry↗

bioRxiv2023

Myostatin is a major endocrine driver of follicle-stimulating hormone synthesis

Myostatin is a paracrine myokine that regulates muscle mass in a variety of species, including humans. Here, we report a functional role for myostatin as an endocrine hormone directly promoting pituitary follicle-stimulating hormone (FSH) synthesis and thereby ovarian function. Previously, this FSH-stimulating role was attributed to other members of the transforming growth factor {beta} family, the activins. The results both challenge activins eponymous role in FSH synthesis and establish an endocrine axis between skeletal muscle and the pituitary gland. The data also suggest that efforts to antagonize myostatin to treat muscle wasting disorders may have unintended consequences on fertility. One-Sentence SummaryHormone synthesis and reproduction depend on crosstalk between skeletal muscle and the pituitary gland.

physiology↗

bioRxiv2023

Wall-following: phylogenetic context of an enhanced behaviour in stygomorphic Sinocyclocheilus (Cypriniformes: Cyprinidae) cavefishes

With 75 known species, the freshwater-fish genus Sinocyclocheilus is the largest cavefish radiation in the world, emerging as a model system for evolutionary studies. They show multiple adaptations for cave dwelling (stygomorphic adaptations), which include a range of traits such as eye degeneration (Normal-eyed, Micro-eyed and Eyeless), depigmentation of skin, and in some species, the presence of "horns". Their behavioural adaptations to subterranean environments, however, are poorly understood. Wall-following (WF) behaviour, where an organism remains in close contact with the boundary demarcating its habitat when in the dark, is a peculiar behaviour observed in a wide range of animals and is enhanced in some cave dwellers. Hence, we hypothesize wall-following to be present also in Sinocyclocheilus, possibly enhanced in Eyeless species compared to species with visual cues (Normal / Micro-eyed species). Using 13 species representative of Sinocyclocheilus radiation and eye-morphs, we designed a series of assays, based on pre-existing methods for Astyanax mexicanus behavioural experiments, to examine wall-following behaviour under three stimulation conditions. Our results indicate that eyeless species exhibit significantly enhanced levels of WF compared to Normal-eyed species, with Micro-eyed forms demonstrating intermediate levels. Using a mtDNA based dated phylogeny (chronogram with four clades A - D), we traced the degree of WF of these forms to outline common patterns. We show that intensity of WF behaviour is high in the subterranean clades (B & C) compared to clades with free-living species (A & D). Experiments on WF behaviour revealed that eyeless species are highly sensitive to vibrations, whereas normal-eyed species are the least sensitive. Since WF behaviour is present to some degree in all Sinocyclocheilus species, and given that these fishes evolved in the late Miocene, we identify this behaviour as being ancestral with WF enhancement related to cave occupation. Our results from this diversification-scale study of cavefish behaviour suggest that enhanced wall-following behaviour may be a convergent trait across all stygomorphic cavefish lineages. Significance statementSinocyclocheilus, a genus of 75 species of freshwater cavefish, is an emerging model system in evolutionary studies. Their adaptations for subterranean life, including eye degeneration, skin depigmentation, and horn-like structures, are well-known, but their behavioural adaptations remain understudied. Here we focus on a phenomenon, called "wall-following," where fish stay close to the cave walls in absence of light. We hypothesized that this behaviour would be more pronounced in eyeless species. We selected 13 species, representative of the diversity of the genus and eye types, and observed their wall-following behaviour under different conditions. Results were intriguing; eyeless species exhibited heightened wall-following behaviour compared to their sighted counterparts, with small-eyed species falling in between. Researchers also mapped this behaviour on a phylogenetic tree, discovering a pattern: cave-dwelling clades showed stronger wall-following than free-living ones. Wall-following is prevalent in all Sinocyclocheilus species and, given the evolutionary history of the genus, is considered an ancestral behaviour that intensified with cave adaptation. These findings contribute to our understanding of convergent evolution, suggesting that enhanced wall-following may be a shared trait among diverse cavefish lineages.

animal behavior and cognition↗

bioRxiv2023

WGCNA and Machine Learning for Screening Potential Biomarkers in traumatic brain injury

BackgroundTraumatic brain injury (TBI) is more common than ever and is becoming a global public health issue. However, there are no sensitive diagnostic or prognostic biomarkers to identify TBI, which leads to long-term consequences. In this study, we aim to identify genes that contribute to brain injury and to identify potential mechanisms for its progression in the early stages. MethodFrom the Gene Expression Omnibus (GEO) database, we downloaded GSE2871s gene expression profiles. Weighted gene coexpression network analyses (WGCNA) were conducted on differentially expressed genes (DEGs), and the DEGs were analyzed by Gene Set Enrichment Analysis(GSEA). An enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed for understanding the biological functions of genes. The potential biomarkers were identified using 3 kinds of machine learning algorithms. Nomogram was constructed using the "rms" package. And the receiver operating characteristic curve (ROC) was plotted to detect and validate our prediction model sensitivity and specifificity. ResultsBetween samples with and without brain injury, 107 DEGs were identified, including 47 upregulated genes and 60 downregulated genes. On the basis of WGCNA and DEGs, 97 target genes were identified. In addition, biological function analysis indicated that target genes were primarily involved in the interaction of neuroactive ligands with receptors, taste transduction, cortisol synthesis and secretion, potassium ion transport. Based on machine learning algorithms, LOC103691092, Npw could be potentially useful biomarkers for TBI and showed good diagnostic values. Finally, a nomogram was constructed of the expression levels of these seven target genes to predict level of TBI, and the ROC showed that these genes can be used as hub genes after TBI. ConclusionLOC103691092, NPW, STK39, KCND3, APOC3, FOXE3, and CHRNB1 were identified as hub genes of TBI. These findings can provide a new direction for the diagnosis and treatment of TBI.

neuroscience↗

bioRxiv2023

β1 integrins regulate cellular behaviors and cardiomyocyte organization during ventricular wall formation

AimsThe mechanisms regulating the cellular behavior and cardiomyocyte organization during ventricular wall morphogenesis are poorly understood. Cardiomyocytes are surrounded by extracellular matrix (ECM) and interact with ECM via integrins. This study aims to determine whether and how {beta}1 integrins regulate cardiomyocyte behavior and organization during ventricular wall morphogenesis in the mouse. Methods and ResultsWe applied mRNA deep sequencing and immunostaining to determine the expression repertoires of /{beta} integrins and their ligands in the embryonic heart. Integrin {beta}1 subunit ({beta}1) and some of its ECM ligands are asymmetrically distributed and enriched in the luminal side of cardiomyocytes, while fibronectin surrounds cardiomyocytes, creating a network for them. Itgb1, which encodes the {beta}1 integrin subunit, was deleted via Nkx2.5Cre/+ to generate myocardial-specific Itgb1 knockout (B1KO) mice. B1KO hearts display an absence of trabecular zone but a thicker compact zone. The abundances of hyaluronic acid and versican are not significantly different. Instead, fibronectin, a ligand of {beta}1, was absent in B1KO. We examined cellular behaviors and organization via various tools. B1KO cardiomyocytes display a random cellular orientation and fail to undergo perpendicular cell division, be organized properly, and establish the proper tissue architecture to form trabeculae. The reduction of Notch1 activation was not the cause of the abnormal cellular organization in B1KO hearts. Mosaic clonal lineage tracing shows that Itgb1 regulates cardiomyocyte transmural migration and proliferation autonomously. Conclusions{beta}1 is asymmetrically localized in the cardiomyocytes, and its ECM ligands are enriched in the luminal side of the myocardium and surrounding cardiomyocytes. {beta}1 integrins are required for cardiomyocytes to attach to the ECM network. This engagement provides structural support for cardiomyocytes to maintain shape, undergo perpendicular division, and establish cellular organization. Deletion of Itgb1, leading to ablation of {beta}1 integrins, causes the dissociation of cardiomyocytes from the ECM network and failure to establish tissue architecture to form trabeculae.

developmental biology↗

bioRxiv2023

Schisandrin B suppresses colon cancer growth by inducing cell cycle arrest and apoptosis via the CHOP signalling pathway

Colon cancer is among the most lethal and prevalent malignant tumours in the world, and the lack of effective therapies highlights the need for novel therapeutic approaches. Schisandrin B (Sch B), a lignan extracted from the fruit Schisandra chinensis, has been reported for its anti-cancer properties. However, no studies to date have been done to characterise the exact molecular mechanisms regarding the anti-tumorigenic effect of Sch B in colon cancer. A comprehensive analysis of the molecular mechanism for the anti-tumorigenic effect of Sch B on human colon cancer cells was performed using combination of Raman spectroscopy, RNA-seq, computational docking and molecular biological experiments. The in vivo efficacy was evaluated by a mouse xenograft model. Sch B reduced cell proliferation and triggered apoptosis in human colon cancer cell lines. Raman spectroscopy, computational, RNA-seq, molecular and cellular studies revealed that Sch B activated unfolded protein responses by interacting with CHOP and upregulating CHOP, which thereby induced apoptosis. CHOP knockdown alleviated the Sch B-induced reduction in cell viability and apoptosis. Sch B reduced colon tumour growth in vivo. Our findings provide essential background for clinical trials examining the effects of Sch B in patients with colon cancer.

pharmacology and toxicology↗

bioRxiv2023

A hybrid machine learning and regression method for cell type deconvolution of spatial barcoding-based transcriptomic data

Spatial barcoding-based transcriptomic (ST) data require cell type deconvolution for cellular-level downstream analysis. Here we present SDePER, a hybrid machine learning and regression method, to deconvolve ST data using reference single-cell RNA sequencing (scRNA-seq) data. SDePER uses a machine learning approach to remove the systematic difference between ST and scRNA-seq data (platform effects) explicitly and efficiently to ensure the linear relationship between ST data and cell type-specific expression profile. It also considers sparsity of cell types per capture spot and across-spots spatial correlation in cell type compositions. Based on the estimated cell type proportions, SDePER imputes cell type compositions and gene expression at unmeasured locations in a tissue map with enhanced resolution. Applications to coarse-grained simulated data and four real datasets showed that SDePER achieved more accurate and robust results than existing methods, suggesting the importance of considering platform effects, sparsity and spatial correlation in cell type deconvolution.

bioinformatics↗

bioRxiv2023

Diversity of Bathyarchaeia viruses in metagenomes and virus-encoded CRISPR system components

Bathyarchaeia represent a class of archaea common and abundant in sedimentary ecosystems. The virome of Bathyarchaeia so far has not been characterized. Here we report 56 metagenome-assembled genomes of Bathyarchaeia viruses identified in metagenomes from different environments. Gene sharing network and phylogenomic analyses led to the proposal of four virus families, including viruses of the realms Duplodnaviria and Adnaviria, and archaea-specific spindle-shaped viruses. Genomic analyses uncovered diverse CRISPR elements in these viruses. Viruses of the proposed family Fuxiviridae harbor an atypical type IV-B CRISPR-Cas system and a Cas4 protein that might interfere with host immunity. Viruses of the family Chiyouviridae encode a Cas2-like endonuclease and two mini-CRISPR arrays, one with a repeat identical to that in the host CRISPR array, potentially allowing the virus to recruit the host CRISPR adaptation machinery to acquire spacers that could contribute to competition with other mobile genetic elements or to inhibition of host defenses. These findings present an outline of the Bathyarchaeia virome and offer a glimpse into their counter-defense mechanisms.

microbiology↗