Biology subjects

Chai, X.

Publications and source records attributed to Chai, X..

At least 19 recordsLinked to original sources

bioRxiv2026

AFP-R: An Open Resource Dedicated to Antifreeze Proteins

Antifreeze proteins (AFPs), lower the freezing point via thermal hysteresis activity and/or ice recrystallization inhibition, playing a crucial role in protecting organisms from freezing damage under sub-zero milieu. This property endows them with promising applications in biomedicine and agriculture, ranging from tissue-organ cryopreservation to the development of frost-resistant crops. However, the lack of comprehensive resources dedicated for AFPs hinders further progress in elucidating their functional mechanisms and advancing their applications. Here, we report AFP-R, an online resource comprising AFP-DB and AFP-Predictor. AFP-DB is a comprehensive database with manually curated proteins bearing experimentally validated antifreeze activity derived from published literature, whereas AFP-Predictor is a sequence-based machine-learning model to identify AFPs. AFP-DB stores diverse AFP-related information, including sequences, structures, post-translational modifications, taxonomy and annotations of antifreeze-activity experimental assays. It now holds 186 entries, 607 sub-entries, and 1444 experimental records. AFP-Predictor, an AFP-identification algorithm built on protein language model ESM2 (Evolutionary Scale Modeling2), is trained on data in AFP-DB and outperforms several existing models. This work offers a valuable resource for systematically dissecting the mechanisms underlying AFP antifreeze activity and will facilitate their broader applications.

bioinformatics↗

bioRxiv2026

Telomere variant sequences encode the genetic blueprint for allele-specific telomere length

The ends of human chromosomes are capped by specialized nucleoprotein structures known as telomeres, which are essential for genome stability. Recent advances in long-read sequencing have enabled allele-specific telomere length measurements at nucleotide resolution, uncovering extreme heterogeneity in telomere length between alleles that is determined at birth and gradually shortens with age. However, the mechanisms underlying allele-specific telomere maintenance and its stability remain poorly understood. Here, we developed a high-resolution workflow combining PacBio and Nanopore long-read sequencing platforms to map allele-specific telomere length in clinical patient samples as well as telomerase-positive cancer cell lines. By tracing allele-specific telomeric sequence in family members across multiple generations, we show that telomeric variant sequences (TVSs) interspersed throughout the canonical repeat region are heritable (with mean similarity score > 0.95), allele-specific, and account for the extreme heterogeneity of telomere length between alleles. Targeted deletion of allele-specific TVSs using CRISPR-Cas9 resets telomere length, further confirming their causal role in the control of allele-specific telomere maintenance. Continuous cell proliferation likely drives the slow but stochastic evolution of allele-specific TVSs distribution, resulting in asymmetry in telomere inheritance from father and mother (p-value < 0.045). These results illustrate how the telomere inheritance may predict allele-specific vulnerability in telomere protection, providing a new paradigm for personalized telomere profiling in aging-related diseases.

genetics↗

bioRxiv2026

Discovery of an NRAS isoform and activation-state selective macrocyclic peptide

Macrocyclic peptides have gained increased attention amid claims they are a "Goldilocks" therapeutic modality that can encode the selectivity of a biologic in a footprint close to that of a small molecule. Here we attempt to find a peptide that binds selectively to NRAS, sparing HRAS and KRAS, while accessing the cytosol via passive cell permeability. To do so, we combine subtractive affinity selection with mRNA display to identify Compound 1, an 11mer macrocyclic peptide which binds NRAS at a novel allosteric site between Helix 3 and Helix 4 of the GTPase domain. Compound 1 has total isoform selectivity and can be tuned to achieve activation-state selectivity with a single amino acid change. While it has preferential affinity for oncogenic NRAS-specific mutations, it does not inhibit NRAS function or achieve passive membrane permeability.

cancer biology↗

bioRxiv2026

C1qa⁺ muscularis macrophages maintain enteric synaptic homeostasis to regulate gastrointestinal motility

The enteric nervous system (ENS) is a complex peripheral neural network that coordinates gastrointestinal motility through highly organized synaptic communication. Although tissue-resident muscularis macrophages (MMs) closely associate with enteric neurons, whether they regulate enteric synaptic organization remains unknown. In the central nervous system (CNS), microglia sculpt neural circuits through complement-dependent synaptic remodeling, raising the possibility that analogous neuroimmune mechanisms operate in the gut. Here, we identify a previously unrecognized role for C1qa{square} MMs in regulating enteric synaptic homeostasis and gastrointestinal motility. Using macrophage-specific constitutive and inducible C1qa deletion models, single-cell RNA sequencing, enteric synaptosome proteomics, physiology, and advanced imaging, we demonstrate that loss of MMs-derived C1qa increases enteric synaptic density without altering neuronal numbers. C1qa deficiency induced broad transcriptional changes in enteric neurons and macrophages, including altered synapse-associated, lysosomal, and endocytic programs. Proteomic analysis revealed that enteric synapses share a conserved molecular architecture with brain synapses while exhibiting distinct gastrointestinal-specific complement-associated synaptic networks enriched for structural and receptor-localization pathways. Functionally, macrophage-specific C1qa deletion altered excitatory and inhibitory enteric neurotransmission, enhanced cholinergic signaling, reduced nitrergic responses, and accelerated gastrointestinal transit, while smooth muscle responsiveness remained preserved. C1qa{square} MMs displayed transcriptional and functional features consistent with a phagocytic synapse-remodeling phenotype, including enrichment of complement, lysosomal, and engulfment pathways. Loss of C1qa impaired macrophage phagocytic activity both in vitro and in vivo and was associated with synapse accumulation and altered macrophage morphology. Importantly, inducible deletion of C1qa in adulthood recapitulated the synaptic and motility phenotypes, demonstrating that C1qa{square} MMs continuously regulate enteric synaptic organization beyond development. Together, these findings identify a complement-dependent neuroimmune mechanism that regulates enteric circuit organization and gut motility, establishing MMs as active modulators of adult ENS synaptic homeostasis. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=117 SRC="FIGDIR/small/729640v1_ufig1.gif" ALT="Figure 1"> View larger version (52K): org.highwire.dtl.DTLVardef@16aadd8org.highwire.dtl.DTLVardef@bb74f3org.highwire.dtl.DTLVardef@fb040corg.highwire.dtl.DTLVardef@1c6e4a5_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2026

Mirror-image mRNA display uncovers isoform-selective D-peptide macrocycles targeting a cryptic KRAS pocket

Activating KRAS mutations drive millions of cancers diagnosed worldwide,1 yet for decades this oncoprotein was deemed "undruggable", reflecting the challenge of discovering molecules capable of perturbing its complex biological functions, and of translating these discoveries into effective cancer therapeutics.2 Recent advances propelled by innovative screening have identified diverse modalities that bind at or near the switch-II pocket (SII-P) of RAS proteins, including molecular glues,3 macrocyclic peptides,4 fragment-derived small molecules,5 and approved therapies that covalently target KRASG12C.6,7 Unfortunately, resistance to approved therapies has emerged,8,9 highlighting the need for molecules that engage new or underexploited binding sites on RAS oncoproteins with mechanisms complementary to established SII-P inhibitors.10,11 Here we show that mirror-image mRNA display12 enabled the discovery of all-D macrocyclic peptide ligands targeting a cryptic RAS back pocket (CRB-P).13 These ligands engage KRAS(OFF) and KRAS(ON) with equal affinity, exploit a single-residue difference among isoforms to bind KRAS selectively, and successfully inhibit oncogenic signaling in KRAS-mutant cells through a mechanism distinct from SII-P binders. Mirror-image screening directly afforded nanomolar peptide ligands stable toward cellular proteolysis and delivered probes targeting distinct epitopes not accessible by homochiral peptide-display methods. Together, these findings establish the CRB-P as a specifically druggable and mechanistically differentiated site on KRAS with potential for combination with emerging RAS-targeting therapies and substantiate mirror-image mRNA display as a strategy for discovering stable all-D macrocyclic peptides targeting previously inaccessible epitopes on challenging targets.

cancer biology↗

bioRxiv2026

Fiber-tract development contributes to functional specialization in the human hippocampus

Fiber-tracts exhibit distinct projection patterns along the anterior-posterior axis of the hippocampus, promoting a specialization in function. This specialization becomes increasingly pronounced throughout child development, with important implications for neurocognitive outcomes. Developmental changes in fiber-tract properties, including intra-axonal cross-sectional area and myelin content, may contribute to this anterior-posterior functional specialization. To test this, we developed a diffusion-MRI tractography pipeline to identify hippocampal fiber-tracts in single subjects, then examined whether age-related differences in total intra-axonal cross-sectional area and myelin content (T1w/T2w) could predict functional specialization in a large cross-sectional sample (N=539, aged 5-21 years). With age, we found that the cross-sectional area of short-range medial-temporal tracts, which primarily target the anterior/body of the hippocampus, exhibited rapid growth. Concomitantly, the cross-sectional area of long-range occipito-parietal tracts, which primarily target the posterior hippocampus, exhibited a modest pruning. Increases in myelin content were relatively homogenous across fiber-tracts. In support of our hypothesis, we found that the cross-sectional area of fiber-tracts significantly predicts the surface-area of an fMRI-defined posterior system; a sensitive marker of functional specialization in the hippocampus. Tracts targeting early visual cortex (V2, V3, V4) showed the strongest association, with statistical modeling indicating a mediating effect of early-visual tract development on the relation between age and functional specialization. These findings provide evidence consistent with a mechanism whereby anatomical neurodevelopment contributes to functional specialization in the human hippocampus.

neuroscience↗

bioRxiv2026

TCR signal strength determines Treg instability and discrimination of self versus non-self antigens

Regulatory T cells (Tregs) expressing autoreactive T-cell receptors (TCRs) maintain immune self-tolerance, yet their fate upon antigen encounter remains unclear. Although selected in the thymus for high-affinity self-recognition, the cross-reactive nature of the TCR repertoire allows some Tregs to also recognize foreign antigens with high affinity. Here, we identify cross-reactive destabilization, a process in which high-affinity recognition of foreign antigens erodes Treg stability and redirects lineage fate. Using a thymic-derived Treg (tTreg) TCR capable of recognizing both self and foreign antigens distinct from the self-ligand that mediated its thymic selection, we show that stimulation with high-affinity non-self agonists induces Foxp3 loss and conversion into effector-like ex-Tregs, whereas self-antigen stimulation preserves lineage stability. Treg instability also increases with age and correlates with activation, suggesting that cumulative foreign-antigen exposure drives this process. These findings reveal a signal-strength-dependent model in which strong TCR engagement induces cross-reactive destabilization to balance immune responsiveness and self-tolerance. One Sentence SummaryForeign antigen-driven destabilization of Treg cells balances immunity and tolerance

immunology↗

bioRxiv2026

Glucokinase links metabolism and lineage plasticity in neuroendocrine prostate cancer via interaction with AKT1

Cancer cells frequently rewire their metabolism to sustain growth and survival under stress. Despite the critical role of metabolic adaptation in tumorigenesis, how specific metabolic enzymes regulate lineage plasticity remains unclear. Here, through FDG-PET imaging and transcriptomic analyses, we reveal markedly elevated glucose uptake in neuroendocrine prostate cancer (NEPC) and identify glucokinase (GCK) as a MYCN-induced metabolic enzyme. Beyond its metabolic role, GCK is indispensable for maintaining the neuroendocrine lineage of prostate cancer cells by establishing a functional circuit with AKT1 through reciprocal regulation--AKT1 binds and phosphorylates GCK at S373, whereas GCK phosphorylates AKT1 at S473. Pharmacological disruption of this AKT1-GCK axis suppresses tumor growth in NEPC mouse models and patient-derived xenografts. Altogether, our findings uncover both the metabolic and noncanonical kinase functions of GCK and establish the AKT1-GCK axis as a key link between metabolic reprogramming and neuroendocrine lineage transition in prostate cancer.

cancer biology↗

bioRxiv2025

Structural semantic evolutionary distance (SSED) unifies the selection of cancer driver genes across macroevolution and tumorigenesis.

The non-random, site-specific enrichment of somatic mutations in cancer driver genes (CDGs) suggests their emergence is governed by underlying evolutionary constraints. However, quantitative methods to define these constraints and their underlying principles remain underexplored. To address this, we introduce the Structural Semantic Evolutionary Distance (SSED), a metric leveraging the pretrained ESM-3 protein language model to quantify evolutionary divergence within a unified structural semantic space. Our analysis demonstrates that CDGs are subject to persistent structural semantic constraints across species, tolerating a significantly narrower range of structural semantic changes during evolution compared to non-CDGs. Crucially, clinically observed oncogenic mutations follow this same principle, favoring minimal structural perturbation as shaped by long-term gene evolution. Such mutations maintain core protein function while conferring a capacity for immune evasion, thereby driving clonal expansion. Guided by this "evolutionary constraint" framework, we successfully predicted and experimentally validated a previously uncharacterized oncogenic mutation, KRAS R135L, in bronchial epithelial cells. Furthermore, clinical cohort analysis demonstrated that SSED acts as an independent predictor of response to immune checkpoint blockade, offering information orthogonal to tumor mutational burden (TMB). This study unifies the evolutionary principles governing CDGs across macroevolutionary and microevolutionary (tumorigenesis) timescales, elucidates the balance between structural adaptability, functional conservation, and immune pressure, and identifies a novel predictive biomarker for cancer immunotherapy.

genetics↗

bioRxiv2025

Validation and pre-analytical considerations for processing cerebrospinal fluid samples on a high-throughput proximity extension assay platform

BackgroundAnalysis of cerebrospinal fluid (CSF) facilitates the understanding of brain-specific molecular changes that may associate with disease progression. Proximity extension assays (PEA) have been deployed in several CSF studies, however the validation of the assay and impact of freeze-thaw cycles on the protein signal has not been documented. We sought to (1) validate the assay on the PEA platform and (2) evaluate the effect of freeze-thaw cycles on the detectability of analytes on the PEA platform. ResultsWe have validated the PEA with Next Generation Sequencing (NGS) readout assay and report on the detectability and coefficient of variation observed in CSF samples. We have also evaluated proteomic signals with a minimum of 3 and a maximum of 9 freeze thaw cycles and detected very minimal change in signal with increasing cycle number. ConclusionOur study is the first to validate PEA using NGS readout platform with CSF samples. We report lower protein detection rates and higher variability in the expansion panels compared to the original 4 panels, with acceptable variation above detectability threshold. In addition, our work demonstrates that the proteomic signal is robust and continues to be stable across multiple freeze thaw cycles. This is highly impactful to the processing and analysis of clinical samples and facilitates the investigation of samples with variable pre-analytical conditions.

neuroscience↗

bioRxiv2024

Three Subtypes Of Autism Spectrum Disorder With Transcriptomic Signatures Derived From Morphometric Similarity Networks

Autism spectrum disorder (ASD) is a prevalent and highly heterogeneous neurodevelopmental disorder. Previous studies have attempted to identify ASD subgroups by analyzing isolated cortical structural features. However, these studies have not considered the relationship between multiple structural features, which provide information on the structural organization of the brain. Morphometric similarity network (MSN), a structural brain network contributed by multiple anatomical features (gray matter volume, mean cortical thickness, surface area, mean curvature, Gaussian curvature, curvature index, and fold index), strongly relates to cytoarchitectonic and genomic measures of histological similarity between cortical areas. We applied K-means clustering on MSN from 236 individuals with ASD and identified three subtypes. Subtype-1 showed relatively similar MSN values with typically developmental individuals (TD). Subtype-2 showed higher morphometric similarities in the lateral frontal and temporal cortical regions and lower in anterior prefrontal and occipital regions compared to TD. These patterns were the opposite in subtype-3. Behaviorally, subtype-3 had more severe verbal and social deficits compared to subtype-2. The weaker resting-state functional connectivity (rs-FC) between the language and salience networks was observed between subtype-2 and TD. Subtype-3 had stronger rs-FC between salience and default mode networks (DMN), between frontoparietal and visual networks, and between language and dorsal attention networks, while weaker rs-FC within DMN, within sensorimotor, and within salience networks. In addition, genes with expression patterns associated with regional MS changes in ASD subtypes were functionally enriched in neuron-specific biological processes related to nervous system development, synaptic signaling and chromatin organization. These genes were particularly enriched in GABAergic neurons, glutamatergic neurons, astrocytes and microglia. Taken together, our findings suggest the existence of different neuroanatomical subtypes based on multiple anatomical features in ASD with distinct transcriptomic signatures and functional connectome patterns.

neuroscience↗

bioRxiv2024

Human transcription factor combinations mapped by genome-wide footprinting with deaminase

An individuals somatic cells have the same genome but exhibit cell-type-specific transcriptome regulated by a combination of transcription factors (TFs) for each gene. Mapping of TF sites on the human genome is critically important for understanding functional genomics. Here we report a novel technique to measure human TFs binding sites genome-wide with single-base resolution by footprinting with deaminase (FOODIE). Single-molecule sequencing reads from thousands of cells after in situ deamination yielded site-specific TF binding fractions and the cooperativity among adjacent TFs. In a human lymphoblastoid cell line, we found that genes in a correlated gene module (CGM) share TF(s) in their cis-regulatory elements to participate a particular biological function. Finally, single-cell resolved experiments (scFOODIE) allow cell-type-specific TF footprinting in heterogeneous brain tissues.

genomics↗

bioRxiv2023

ProFAST: a fast and scalable factor analysis for spatially aware dimension reduction of multi-section spatial transcriptomics data

Biological techniques for spatially resolved transcriptomics (SRT) have advanced rapidly in both throughput and spatial resolution for a single spatial location. This progress necessitates the development of efficient and scalable spatial dimension reduction methods that can handle large-scale SRT data from multiple sections. Here, we developed FAST as a fast and efficient generalized probabilistic factor analysis for spatially aware dimension reduction, which simultaneously accounts for the count nature of SRT data and extracts a low-dimensional representation of SRT data across multiple sections, while preserving biological effects with consideration of spatial smoothness among nearby locations. Compared with existing methods, FAST uniquely models the count data across multiple sections while using a local spatial dependence with scalable computational complexity. Using both simulated and real datasets, we demonstrated the improved correlation between FAST estimated embeddings and annotated cell/domain types. Furthermore, FAST exhibits remarkable speed, with only FAST being applicable to analyze a mouse embryo Stereo-seq dataset with >2.3 million locations in only 2 hours. More importantly, FAST identified the differential activities of immune-related transcription factors between tumor and non-tumor clusters and also predicted a carcinogenesis factor CCNH as the upstream regulator of differentially expressed genes in a breast cancer Xenium dataset.

genomics↗

bioRxiv2022

Anti-phasic oscillatory development for speech and noise processing in cochlear implanted toddlers

Human brain demonstrates amazing readiness for speech and language learning at birth, but the auditory development preceding such readiness remains unknown. Cochlear implanted (CI) children with prelingual deafness provide a unique opportunity to study this developmental stage. Using functional near-infrared spectroscopy, we revealed that the brain of CI children was nearly irresponsive to sounds at CI hearing onset. With increasing CI experiences up to 32 months, the brain demonstrated function, region and hemisphere specific development. Most strikingly, the left anterior temporal lobe showed an oscillatory trajectory, changing in opposite phases for speech and noise. In addition, speech responses increased linearly in left sylvian parieto-temporal area and right inferior frontal gyrus, and noise responses changed in U shape in right supramarginal gyrus. Such cortical development predicted behavioral improvement. The study provides the first longitudinal brain imaging evidence for early auditory development preceding speech acquisition in the human brain. Graphic abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=120 SRC="FIGDIR/small/483211v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@d84974org.highwire.dtl.DTLVardef@1be9ba0org.highwire.dtl.DTLVardef@db5fb7org.highwire.dtl.DTLVardef@68f420_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIThe brain of cochlear implanted toddlers is functionally inferior to neonates C_LIO_LIHearing experiences drive functional development in auditory related cortical areas C_LIO_LISpeech and noise processing develop in anti-phasic oscillatory trajectories C_LIO_LIAuditory cortical development predicts post-implantation behavioral improvement C_LI

neuroscience↗

bioRxiv2021

Oxidative phosphorylation safeguards pluripotency via UDP-N-acetylglucosamine

The roles of mitochondrial respiration in pluripotency remain largely unknown. We show here that mouse ESC mitochondria possess superior respiration capacity compared to somatic cell mitochondria, and oxidative phosphorylation (OXPHOS) generates the majority of cellular ATP in ESCs. Inhibition of OXPHOS results in extensive pluripotency and metabolic gene expression reprogram, leading to disruption of self-renewal and pluripotency. Metabolomics profiling identifies UDP-N-acetylglucosamine (UDP-GlcNAc) as one of the most significantly decreased metabolites in response to OXPHOS inhibition. The loss of ESC identity induced by OXPHOS inhibition can be ameliorated by directly adding GlcNAc both in vitro and in vivo. This work demonstrates that mitochondrial respiration, but not glycolysis, produces the majority of ATP in ESCs, and uncovers a novel mechanism whereby mitochondrial respiration is coupled with the hexosamine biosynthesis pathway to generate UDP-GlcNAc for ESC identity maintenance. SIGNIFICANCEOxidative phosphorylation (OXPHOS) and glycolysis are the two major pathways for generating ATP in mammalian cells. It is widely assumed that somatic cells utilize OXPHOS, whereas embryonic stem cells (ESCs) utilize glycolysis with low mitochondrial respiration rates even under aerobic conditions. However, the relative contribution of OXPHOS and glycolysis to ATP generation in ESCs, and the role of mitochondrial respiration in regulating ESC identity, have remained unclear. In this study, Cao et al demonstrate that mouse ESC mitochondria have a significantly higher respiration capacity than somatic cell mitochondria. Oxidative phosphorylation produces the majority of cellular ATP in mESCs and is coupled with the hexosamine biosynthesis pathway to generate UDP-GlcNAc for pluripotency maintenance. These findings define the function and mechanism of OXPHOS in regulating pluripotency, and challenge the traditional concept that mESCs rely on glycolysis over OXPHOS for their major supply of energy. HIGHLIGHTSO_LIESC mitochondria have a significantly higher respiration capability than somatic cell mitochondria C_LIO_LIOXPHOS, but not glycolysis, produces the majority of cellular ATP in ESCs C_LIO_LIOXPHOS inhibition induces a decrease in O-GlcNAcylation and the expression of pluripotency genes in blastocysts that can be partially rescued by adding GlcNAc C_LIO_LIOXPHOS is coupled with the hexosamine biosynthesis pathway for UDP-GlcNAc biosynthesis to maintain ESC identity C_LI

cell biology↗

bioRxiv2020

Cancer SIGVAR: A semi-automated interpretation tool for germline variants of hereditary cancer-related genes

The American College of Medical Genetics and Genomics and the Association for Molecular Pathology published guidelines in 2015 for the clinical interpretation of Mendelian disorder sequence variants based on 28 criteria. ClinGen Sequence Variant Interpretation (SVI) Working Groups have developed many adaptations or refinements of these guidelines to improve the consistency of interpretation. We combined the most recent adaptations to expand the criteria from 28 to 48 and developed a tool called Cancer SIGVAR to help healthcare workers and genetic counselors interpret the clinical significance of cancer germline variants, which is critical for the clinical diagnosis and treatment of hereditary cancer. Our tool can accept VCF files as input and realize fully automated interpretation based on 21 criteria and semi-automated interpretation based on 48 criteria. We validated our tool on the ClinVar and CLINVITAE benchmark databases for the accuracy of fully automated interpretation, achieving an average consistency for pathogenic and benign assessment up to 93.40% and 82.54%, respectively. We compared Cancer SIGVAR with a similar tool, InterVar, and analyzed the main differences in criteria and implementation. In addition, to verify the performance of semi-automated interpretation based on 48 criteria, we selected 911 variants from two benchmark databases and reached an average classification consistency of 98.35%. Our findings highlight the need to optimize automated interpretation tools based on constantly updated guidelines.

genetics↗

bioRxiv2020

Specific ACE2 Expression in Cholangiocytes May Cause Liver Damage After 2019-nCoV Infection

A newly identified coronavirus, 2019-nCoV, has been posing significant threats to public health since December 2019. ACE2, the host cell receptor for severe acute respiratory syndrome coronavirus (SARS), has recently been demonstrated in mediating 2019-nCoV infection. Interestingly, besides the respiratory system, substantial proportion of SARS and 2019-nCoV patients showed signs of various degrees of liver damage, the mechanism and implication of which have not yet been determined. Here, we performed an unbiased evaluation of cell type specific expression of ACE2 in healthy liver tissues using single cell RNA-seq data of two independent cohorts, and identified specific expression in cholangiocytes. The results indicated that virus might directly bind to ACE2 positive cholangiocytes but not necessarily hepatocytes. This finding suggested the liver abnormalities of SARS and 2019-nCoV patients may not be due to hepatocyte damage, but cholangiocyte dysfunction and other causes such as drug induced and systemic inflammatory response induced liver injury. Our findings indicate that special care of liver dysfunction should be installed in treating 2019-nCoV patients during the hospitalization and shortly after cure.

genomics↗

bioRxiv2020

A strategy for complete telomere-to-telomere assembly of ciliate macronuclear genome using ultra-high coverage Nanopore data

Ciliates contain two kinds of nuclei: the germline micronucleus (MIC) and the somatic macronucleus (MAC) in a single cell. The MAC usually have fragmented chromosomes. These fragmented chromosomes, capped with telomeres at both ends, could be gene size to several megabases in length among different ciliate species. So far, no telomere-to-telomere assembly of entire MAC genome in ciliate species is finished. Development of the third generation sequencing technologies allows to generate sequencing reads up to megabases in length that could possibly span an entire MAC chromosome. Taking advantage of ultra-long Nanopore reads, we established a simple strategy for the complete assembly of ciliate MAC genomes. Using this strategy, we assembled the complete MAC genomes of two ciliate species Tetrahymena thermophila and Tetrahymena shanghaiensis, composed of 181 and 214 chromosomes telomere-to-telomere respectively. The established strategy as well as the high-quality genome data will provide a useful approach for ciliate genome assembly, and a valuable community resource for further biological, evolutionary and population genomic studies.

genomics↗