Biology subjects

Hao, K.

Publications and source records attributed to Hao, K..

At least 19 recordsLinked to original sources

bioRxiv2026

Macrophage-derived IL-27 sustains autoreactive CD8+ cytotoxic T cells in autoimmune hepatitis

Chronic or persistent T cell activation is widely thought to culminate in T cell exhaustion, yet how autoreactive CD8+ T cells remain functionally intact despite sustained self-antigen exposure is poorly understood. In chronic infection and cancer this durability is attributed to stem-like, TCF1+ PD-1+ progenitor-exhausted (Tpex) cells that reside in lymphoid tissue and continuously replenish functional effectors; whether such a reservoir operates within a chronically inflamed peripheral organ during sterile autoimmunity is unknown. Here we show that mice lacking the lysosomal nuclease DNase2a together with the type I interferon receptor Ifnar1 (Dnase2a-/- Ifnar1-/-) develop spontaneous, progressive hepatic inflammation. This hepatitis was dependent on the endosomal DNA sensor TLR9, identifying self-DNA as the initiating ligand. Inflammation was marked by expansion of inflammatory macrophages and accumulation of CD8+ T cells co-expressing PD-1 and TOX that retained, rather than lost, effector function. Paired single-cell TCR and transcriptomic analysis revealed progenitor-exhausted T cells within the liver itself that shared clonotypes with clonally expanded PD-1+ TOX+ T cells, defining a locally operating progenitor-to-effector pipeline. Spatial transcriptomics positioned these intrahepatic T cell clusters adjacent to IL-27-expressing inflammatory macrophages, and disruption of IL-27 or its receptor in bone marrow-derived cells reduced PD-1+ CD8+ T cells and their effector functions. These findings define a novel mechanism for sustaining autoreactive T cells in the liver via TLR9-driven macrophage-induced IL-27 circuit that sustains a functional, self-renewing autoreactive PD-1+ CD8+ T cell program in situ.

immunology↗

bioRxiv2026

Substrate recognition and ion coupling mechanism of the human VIAAT

Inhibitory neurotransmission, essential for neural circuit homeostasis and proper neurological function, depends on the efficient sequestration of {gamma}-aminobutyric acid (GABA) and glycine into synaptic vesicles. This critical process is mediated exclusively by the vesicular inhibitory amino acid transporter (VIAAT). Despite extensive biochemical and physiological investigation, the molecular mechanism governing VIAAT-mediated transport has remained incompletely understood. Here, we determined structures of human VIAAT in multiple functional states, including apo, GABA-bound, and glycine-bound states, as well as apo state in chloride-free condition. VIAAT adopts a classical LeuT-fold and we elucidated how its large, electronegative binding pocket accommodates both GABA and glycine. Moreover, we resolved two previously unidentified chloride-binding sites. Through integrative molecular dynamics simulations and functional mutagenesis, our results support roles for chloride and the conserved residue E213 in substrate binding and proton-coupled transport. Together, our findings establish a structural framework for VIAAT-mediated inhibitory neurotransmitter transport that illuminates the molecular basis of inhibitory synaptic transmission and provides a foundation for understanding VIAAT dysfunction in epilepsy and related neurodevelopmental disorders.

neuroscience↗

bioRxiv2026

Circuit-Specific Resting-State fMRI Signatures for Stratifying First-Episode Major Depressive Disorder and Predicting Recurrence Risk

BackgroundDepression is biologically heterogeneous, and first-episode depression (FED) carries a high risk of recurrence that is poorly captured by symptom-based assessment. Early identification of patients likely to relapse, as well as reliable identification of those unlikely to relapse, is needed to support personalized intervention and efficient allocation of care. MethodsWe developed a neurocomputational framework to infer recurrence risk from resting-state fMRI functional connectivity. The framework combines a Convolutional Filtering Autoencoder (CFAE) with a k-medoids clustering algorithm (FED-kMC) to derive neurofunctional FED subtypes, followed by a Manifold Sheaves-based Ensemble Support Vector Machine (MST-LVSVM) to estimate individual-level recurrence risk and define an interpretable decision boundary. Circuit-level analyses were then used to localize connectivity pathways associated with high relapse risk. ResultsThe framework identified two neurofunctionally distinct FED subtypes with divergent recurrence trajectories and achieved an external validation accuracy of 82.61% for recurrence risk prediction. Circuit analyses highlighted dysfunction within the Medial Superior Frontal Gyrus-Hippocampus and Angular Gyrus-Precuneus pathways as neural correlates of high relapse risk, together with a decision boundary enabling early-stage risk stratification. ConclusionsIntegrating connectome-derived, circuit-level information with subtype-aware machine learning may support proactive identification of FED patients at elevated recurrence risk and facilitate targeted early interventions, bridging connectome-level analysis and clinical decision-making.

neuroscience↗

bioRxiv2024

Reconstructing signaling history of single cells with imaging-based molecular recording

The intensity and duration of biological signals encode information that allows a few pathways to regulate a wide array of cellular behaviors. Despite the central importance of signaling in biomedical research, our ability to quantify it in individual cells over time remains limited. Here, we introduce INSCRIBE, an approach for reconstructing signaling history in single cells using endpoint fluorescence images. By regulating a CRISPR base editor, INSCRIBE generates mutations in genomic target sequences, at a rate proportional to signaling activity. The number of edits is then recovered through a novel ratiometric readout strategy, from images of two fluorescence channels. We engineered human cell lines for recording WNT and BMP pathway activity, and demonstrated that INSCRIBE faithfully recovers both the intensity and duration of signaling. Further, we used INSCRIBE to study the variability of cellular response to WNT and BMP stimulation, and test whether the magnitude of response is a stable, heritable trait. We found a persistent memory in the BMP pathway. Progeny of cells with higher BMP response levels are likely to respond more strongly to a second BMP stimulation, up to 3 weeks later. Together, our results establish a scalable platform for genetic recording and in situ readout of signaling history in single cells, advancing quantitative analysis of cell-cell communication during development and disease.

synthetic biology↗

bioRxiv2024

IFNγ initiates TLR9-dependent autoimmune hepatitis in DNase II deficient mice

Patients with biallelic hypomorphic mutation in DNASE2 develop systemic autoinflammation and early-onset liver fibrosis. Prior studies showed that Dnase2-/- Ifnar-/- double knockout (DKO) mice develop Type I IFN-independent liver inflammation, but immune mechanisms were unclear. We now show that DKO mice recapitulate many features of human autoimmune hepatitis (AIH), including periportal and interstitial inflammation and fibrosis and elevated ALT. Infiltrating cells include CD8+ tissue resident memory T cells, type I innate lymphoid cells, and inflammatory monocyte/macrophage cells that replace the Kupffer cell pool. Importantly, TLR9 expression by bone marrow-derived cells is required for the the development of AIH. TLR9 is highly expressed by inflammatory myeloid cells but not long-lived Kupffer cells. Furthermore, the initial recruitment of TLR9 expressing monocytes and subsequent activation of lymphocytes requires IFN{gamma} signaling. These findings highlight a critical role of feed forward loop between TLR9 expressing monocyte-lineage cells and IFNg producing lymphocytes in autoimmune hepatitis.

immunology↗

bioRxiv2024

Influence of chondroitin sulfate glycan sulfation patterns on histochemical labeling of perineuronal nets- a comparative study of interregional distribution in human and mouse brain

Perineuronal nets (PNNs) are a condensed subtype of extracellular matrix that form a net-like coverings around certain neurons in the brain. PNNs are primarily composed of chondroitin sulfate (CS) proteoglycans from the lectican family that consist of CS-glycosaminoglycan (CS-GAG) side chains attached to a core protein. CS disaccharides can exist in various isoforms with different sulfation patterns. Literature suggests that CS disaccharide sulfation patterns can influence the function of PNNs as well as their labeling. This study was conducted to characterize such interregional CS disaccharide sulfation pattern differences in adult human (N = 81) and mouse (N = 19) brains. Liquid chromatography tandem mass spectrometry was used to quantify five different CS disaccharide sulfation patterns, which were then compared to immunolabeling of PNNs using Wisteria Floribunda Lectin (WFL) to identify CS-GAGs and anti-aggrecan to identify CS proteoglycans. In healthy brains, significant regional and species-specific differences in CS disaccharide sulfation and single versus double-labeling pattern were identified. A secondary analysis to investigate how early-life stress (ELS) impacts these PNN features discovered that although ELS increases WFL+ PNN density, the CS-GAG sulfation code and single versus double PNN-labeling distributions remained unaffected in both species. These results underscore PNN complexity in traditional research, emphasizing the need to consider their heterogeneity in future experiments.

neuroscience↗

bioRxiv2024

Identifying the function of the NMDA NR1C2 subunit through its interaction with Magi-2 during inflammatory pain

Much is understood about the structure and gating properties of NMDA receptors (NMDAR), but the function of the carboxy-terminal splice variant of the NR1 subunit, NR1C2 has never been identified. By studying the scaffolding protein Magi-2 in animal models of inflammatory pain, we discovered how NR1C2 protein is specifically regulated. We found that Magi-2 deficiency resulted in decreased pain behavior and a concomitant reduction in NR1C2 protein. Magi-2 contains WW domains, domains typically found in ubiquitin ligases. We identified an atypical WW-binding domain within NR1C2 which conferred susceptibility to Nedd4-1 ubiquitin-ligase dependent degradation. We used lipidated peptidomimetics derived from the NR1C2 sequence and found that NR1C2 protein levels and pain behavior can be pharmacologically targeted. The function of NR1C2 is to give lability to a pool of NMDAR, important for pain signaling.

neuroscience↗

bioRxiv2022

Spatial Localization Ability of Planarians Identified Through the Light Maze Paradigm

Spatial localization ability is crucial for free-living animals to fit the environment. As shown by previous studies, planarians can be conditioned to discriminate directions. However, due to their simplicity and primitiveness, they had never been considered to have true spatial localization ability to retrieve locations of objects and places in the environment. Here, we introduce a light maze training paradigm to demonstrate that a planarian worm can navigate to a former recognized place from the start point, even if the worm is transferred into a newly produced maze. This finding identifies the spatial localization ability of planarians for the first time, which provides clues for the evolution of spatial learning. Since the planarians have a primitive brain with simple structures, this paradigm can also provide a simplified model for a detailed investigation of spatial learning.

animal behavior and cognition↗

bioRxiv2022

Decoding the Variant-to-Function Relationship for LIPA, a Risk Locus for CAD

Translating human genomic discoveries into mechanistic insights requires linking genetic variations to candidate genes and their causal functional phenotypes. Genome-wide association studies have consistently identified LIPA as a risk locus for coronary artery disease (CAD), with previous expression quantitative trait loci (eQTL) analyses prioritizing LIPA as a candidate causal gene. However, functional studies elucidating the causal variants, regulatory mechanisms, target cell types, and their causal impact on atherosclerosis have been lacking. To address this gap, we applied functional genomics and experimental mouse models to establish the variant-to-function relationship at the LIPA locus. Our findings show that CAD risk alleles in the LIPA locus increase LIPA expression and enzyme activity specifically in monocytes/macrophages by enhancing PU.1 binding to an intronic enhancer region that interacts with the LIPA promoter. In myeloid Lipa-overexpressing mice, we observed larger atherosclerotic lesions accompanied by altered macrophage function, including increased macrophage accumulation due to enhanced monocyte recruitment, reduced neutral lipid accumulation, and upregulation of integrin and extracellular matrix pathways. Our work establishes a direct causal link between LIPA risk alleles and increased monocyte/macrophage LIPA that exacerbates atherosclerosis, bridging human functional genomic evidence to the mechanistic understanding of CAD. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=58 SRC="FIGDIR/small/516293v2_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@11ce287org.highwire.dtl.DTLVardef@15c201aorg.highwire.dtl.DTLVardef@13f90c9org.highwire.dtl.DTLVardef@3aa3be_HPS_FORMAT_FIGEXP M_FIG C_FIG

genomics↗

bioRxiv2022

An e-cigarette aerosol generation, animal exposure and toxicants quantification system to characterize in vivo nicotine kinetics in arterial and venous blood

The increasing e-cigarette use worldwide presents an urgent need to characterize their nicotine delivery property, brain stimulation and potential long-term health effects. We constructed an end-to-end system enabling combustible-cigarette (c-cigarette) and e-cigarette aerosol generation, animal exposure, and effect assessment. The system consists of (1) a 10-channel aerosol generator resembling human smoking/vaping scenarios, (2) nose-only and whole-body exposure chambers suitable for long- or short-duration studies, (3) a lab protocol for animal exposure and collecting arterial and venous blood <1 minute after the exposure, and (4) chromatograph and mass spectrometry to quantify nicotine concentrations in aerosol and biospecimens. We applied the system in a proof-of-principle study characterizing in vivo nicotine delivery after e-cigarette aerosol inhalation. Groups of Sprague-Dawley rats were exposed to e-cigarette aerosols for 1, 2 and 4 minutes, respectively. Arterial and venous blood samples were collected immediately after the exposure. We also directly compared nose-only and whole-body exposure approaches. After nose-only e-cigarette aerosol exposure, the nicotine concentration in arterial blood was substantially higher (11.32 ng/mL in average) than in veins. Similar arterio-venous concentration difference was observed in whole-body exposure experiments. In summary, we described a complete system ideal for e- and c-cigarette in vivo nicotine kinetics and long-term health research. Our findings highlight arterial blood as the suitable bio-specimen for e-cigarette nicotine delivery studies. HighlightO_LIWe constructed a combustible- and e-cigarette aerosol generation - exposure - effect assessment system resembling real world human smoking/vaping scenarios. C_LIO_LIProof-of-principle study characterized in vivo nicotine delivery from e-cigarette aerosol to arterial and venous blood at high temporal resolution. C_LIO_LIAfter exposure, the nicotine concentration was substantially higher (11.32 ng/mL) in arterial blood than in veins. C_LIO_LIOur results suggest arterial blood as the suitable bio-specimen to study nicotine delivery and brain stimulation. C_LI

pharmacology and toxicology↗

bioRxiv2022

Diving Behavior Reveals Humidity Sensing Ability of Water Deprived Planarians

Humidity sensing ability is crucial to terrestrial animals for fitting the environment. Researchers made great progress in recent study about humidity sensing mechanisms of terrestrial animals. However, it is poorly understood whether humidity sensing exists in aquatic animals. Here, we demonstrate that the aquatic planarians, one of the primitive forerunners of later animals, has the ability of humidity sensing and is capable of using the ability to perceive the water beneath itself from a drought place to seek survival. The behavior we discovered is described as diving because the worms twist its body to break away from the mucus that make them adhere to the drought place and drop into the water. The behavior is triggered by rapidly increasing humidity. This finding suggests that humidity sensing ability exists in the lower aquatic animals, and the ability might be used to seek for water when aquatic animals are facing desiccation. The finding also suggests that survival-seeking and decision-making behavior have appeared in the primitive planarian worms.

animal behavior and cognition↗

bioRxiv2021

Isolation and characterization of fucosylated extracellular vesicles based on a novel GlyExo-Capture technique

Owing to their diagnostic and therapeutic potential, extracellular vesicles (EVs) derived from tumour cells have recently garnered great interest. The presence of different glycosylation sites at the EV surface supports the need for efficient glycosylated EV isolation. Here, we developed a GlyExo-Capture technique for robustly capturing fucosylated EVs from sera and cell supernatants. Lens culinaris lectin (LCA)-immobilized magnetic complexes were found to capture approximately 60% of the total EVs from HepG2 cells. The capture efficiency was reduced to less than 40% in nontumorigenic MIHA cells. Notably, the cellular uptake pattern of highly fucosylated EVs was markedly different from that of EVs with low fucosylation. The unearthing of enriched fucosylated EV miRNA cargos by next-generation deep sequencing (NGS) revealed 75 differentially expressed miRNAs (DEMs) in hepatocellular carcinoma (HCC). Among them, a 4-miRNA panel was chosen and yielded an area under the ROC curve (AUC) of 0.86 and 0.84 for the detection of HCC from non-HCC controls in testing samples and independent validation samples, respectively. The 4-miRNA signature was independent of alpha-fetoprotein (AFP), and a combined model with AFP yielded an increased AUC of 0.92. In conclusion, we developed a high-throughput method for capturing fucosylated EVs efficiently and shed light on the use of fucosylated EVs as potential sources of miRNAs for cancer biomarker detection.

cancer biology↗

bioRxiv2021

Transcriptome-wide association study of coronary artery disease identifies novel susceptibility genes

Transcriptome-wide association studies (TWAS) explore genetic variants affecting gene expression for association with a trait. Here we studied coronary artery disease (CAD) using this approach by first determining genotype-regulated expression levels in nine CAD relevant tissues by EpiXcan in two genetics-of-gene-expression panels, the Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task (STARNET) and the Genotype-Tissue Expression (GTEx). Based on these data we next imputed gene expression in respective nine tissues from individual level genotype data on 37,997 CAD cases and 42,854 controls for a subsequent gene-trait association analysis. Transcriptome-wide significant association (P < 3.85e-6) was observed for 114 genes, which by genetic means were differentially expressed predominately in arterial, liver, and fat tissues. Of these, 96 resided within previously identified GWAS risk loci and 18 were novel (CAND1, EGFLAM, EZR, FAM114A1, FOCAD, GAS8, HOMER3, KPTN, MGP, NLRC4, RGS19, SDCCAG3, STX4, TSPAN11, TXNRD3, UFL1, WASF1, and WWP2). Gene set analyses showed that TWAS genes were strongly enriched in CAD-related pathways and risk traits. Associations with CAD or related traits were also observed for damaging mutations in 67 of these TWAS genes (11 novel) in whole-exome sequencing data of UK Biobank. Association studies in human genotype data of UK Biobank and expression-trait association statistics of atherosclerosis mouse models suggested that newly identified genes predominantly affect lipid metabolism, a classic risk factor for CAD. Finally, CRISPR/Cas9-based gene knockdown of RGS19 and KPTN in a human hepatocyte cell line resulted in reduced secretion of APOB100 and lipids in the cell culture medium. Taken together, our TWAS approach was able to i) prioritize genes at known GWAS risk loci and ii) identify novel genes which are associated with CAD.

genetics↗

bioRxiv2021

Variation in Placental microRNA Expression Associates with Familial Cardiovascular Disease

In the United States, cardiovascular disease is the leading cause of death, and the rate of maternal mortality remains among the highest of any industrialized nation. Maternal cardiometabolic health throughout gestation and postpartum is representative of placental health and physiology. Both proper placental functionality and placental microRNA expression are essential to successful pregnancy outcomes, and both are highly sensitive to genetic and environmental sources of variation. While placental pathologies, such as preeclampsia, are associated with maternal cardiovascular health and may contribute to the developmental programming of cardiovascular disease, the role of more subtle alterations to placental function and microRNA expression in this relationship remains poorly understood. To develop a more comprehensive understanding of how cardiometabolic health influences placental microRNA expression, and how this shapes placental functionality, we performed small RNA sequencing to investigate microRNA in the placentae from the Rhode Island Child Health Study (n=230). We modeled microRNA counts on maternal family history of cardiovascular disease using negative binomial generalized linear models, and identified microRNAs that were differential expressed (DEmiRs) at a false discovery rate (FDR) less than 0.10. Utilizing parallel mRNA sequencing data and bioinformatic target prediction software, we identified potential mRNA targets of these DEmiRs. We identified 9 DEmiRs, with predicted targets of those miRNA enriched overwhelmingly in the TGF{beta} signaling pathway but also in pathways involving cellular metabolism and immunomodulation. Overall, we identified a robust association existing between familial cardiovascular disease and placental microRNA expression which may be implicated in both placental insufficiencies and the developmental programming of cardiovascular disease.

genetics↗

bioRxiv2020

LACCASE is Necessary for Root Development in Salvia miltiorrhiza

Laccases are multicopper-containing glycoproteins related to monolignol oxidation and polymerization. These properties indicate that laccases are involved in the formation of important medicinal phenolic acid compounds in Salvia miltiorrhiza such as salvianolic acid B (SAB), which is used for cardiovascular disease treatment. To date, 29 laccases have been found in S. miltiorrhiza, some of which influence the synthesis of phenolic acids. Because of the functional redundancy of laccase genes, their roles in S. miltiorrhiza are poorly understood. In this study, the CRISPR/Cas9 system was first used for dual gene locus targeting in S. miltiorrhiza to knock out multiple laccase family genes. The development of the roots was retarded, and root microstructure was abnormal in laccase mutant lines. Additionally, the accumulation of phenolic acid compounds as well as lignin was dramatically reduced. This study suggests that SmLACs are necessary for root development and phenolic acid compound metabolism in S. miltiorrhiza.

plant biology↗

bioRxiv2020

Research on the Influence of Different Temperature Conditions on the Microbial Community in Anearobic-Anoxic-Oxic process on the Plateau

In order to further understand the influence of different temperature conditions in the low temperature range on the microbial community structure in the Anearobic-Anoxic-Oxic waste water treatment process on the plateau, four temperature conditions were designed in the research, including 25{degrees}C, 20{degrees}C, 15{degrees}C and 10{degrees}C. Each working condition lasted three days. Activated sludge from anaerobic tank, anoxic tank and oxic tank under each working condition was analyzed based on the 16S rRNA high-throughput sequencing technology. The result shows that the plateau temperature conditions have little influence on the level abundance of phylum. Under all conditions, Bacteroidetes, Proteobacteria and Actinobacteria are the main phyla. The abundance of nitrifying bacterium and phosphorus removal bacteria rose in the first three conditions and fell at 10 {degrees}C. The abundance of Denitrification bacteria and Nitrite oxidizing bacteria was significantly higher than that of Ammonia oxidation bacteria and Azotobacter bacteria and Phosphorus-accumulating Organisms(PAO) had an overall advantage over Glycogen-accumulating Organisms (GAO) throughout the research.

microbiology↗

bioRxiv2020

Evolution of regulatory signatures in primate cortical neurons at cell type resolution

The human cerebral cortex contains many cell types that likely underwent independent functional changes during evolution. However, cell type-specific regulatory landscapes in the cortex remain largely unexplored. Here we report epigenomic and transcriptomic analyses of the two main cortical neuronal subtypes, glutamatergic projection neurons and GABAergic interneurons, in human, chimpanzee and rhesus macaque. Using genome-wide profiling of the H3K27ac histone modification, we identify neuron-subtype-specific regulatory elements that previously went undetected in bulk brain tissue samples. Human-specific regulatory changes are uncovered in multiple genes, including those associated with language, autism spectrum disorder and drug addiction. We observe preferential evolutionary divergence in neuron-subtype-specific regulatory elements and show that a substantial fraction of pan-neuronal regulatory elements undergo subtype-specific evolutionary changes. This study sheds light on the interplay between regulatory evolution and cell-type-dependent gene expression programs, and provides a resource for further exploration of human brain evolution and function. SIGNIFICANCEThe cerebral cortex of the human brain is a highly complex, heterogeneous tissue that contains many cell types which are exquisitely regulated at the level of gene expression by non-coding regulatory elements, presumably, in a cell-type-dependent manner. However, assessing the regulatory elements in individual cell types is technically challenging, and therefore, most of the previous studies on gene regulation were performed with bulk brain tissue. Here we analyze two major types of neurons isolated from the cerebral cortex of humans, chimpanzees and rhesus macaques, and report complex patterns of cell-type-specific evolution of the regulatory elements in numerous genes. Many genes with evolving regulation are implicated in language abilities as well as psychiatric disorders.

evolutionary biology↗

bioRxiv2020

Gene Expression Network Analysis Provides Potential Targets Against SARS-CoV-2

ABSTRACTBACKGROUND Cell entry of SARS-CoV-2, the novel coronavirus causing COVID-19, is facilitated by host cell angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). We aimed to identify and characterize genes that are co-expressed with ACE2 and TMPRSS2, and to further explore their biological functions and potential as druggable targets.METHODS Using the gene expression profiles of 1,038 lung tissue samples, we performed a weighted gene correlation network analysis (WGCNA) to identify modules of co-expressed genes. We explored the biology of co-expressed genes using bioinformatics databases, and identified known drug-gene interactions.RESULTS ACE2 was in a module of 681 co-expressed genes; 12 genes with moderate-high correlation with ACE2 (r>0.3, FDR<0.05) had known interactions with existing drug compounds. TMPRSS2 was in a module of 1,086 co-expressed genes; 15 of these genes were enriched in the gene ontology biologic process ‘Entry into host cell’, and 53 TMPRSS2-correlated genes had known interactions with drug compounds.CONCLUSION Dozens of genes are co-expressed with ACE2 and TMPRSS2, many of which have plausible links to COVID-19 pathophysiology. Many of the co-expressed genes are potentially targetable with existing drugs, which may help to fast-track the development of COVID-19 therapeutics.Competing Interest StatementS.M. reports personal fees from Novartis and Boehringer-Ingelheim, outside the submitted work. W.T. reports fees to Institution from Roche-Ventana, AbbVie, Merck-Sharp-Dohme and Bristol-Myers-Squibb, outside the submitted work. M.B. reports research grants paid to University from Astra Zeneca, Novartis, outside the submitted work. D.D.S. reports research funding from AstraZeneca and received honoraria for speaking engagements from Boehringer Ingelheim and AstraZeneca over the past 36 months, outside of the submitted work.View Full Text

genomics↗