Biology subjects

Guo, J.

Publications and source records attributed to Guo, J..

At least 307 records · Page 17Linked to original sources

bioRxiv2021

Structural mechanism of calcium-mediated hormone recognition and Gβ interaction by the human melanocortin-1 receptor

Melanocortins are peptide hormones critical for stress response, energy homeostasis, inflammation, and skin pigmentation. Their functions are mediated by five G protein-coupled receptors (MC1R to MC5R), predominately through the stimulatory G protein (Gs). MC1R, the founding member of melanocortin receptors, is mainly expressed in melanocytes and is involved in melanogenesis. Dysfunction of MC1R is associated with the development of melanoma and skin cancer. Here we present three cryo-electron microscopy structures of the MC1R-Gs complexes bound to endogenous hormone -MSH, a marketed drug afamelanotide, and a synthetic agonist SHU9119. These structures reveal the orthosteric binding pocket for the conserved HFRW motif among melanocortins and the crucial role of calcium ion in ligand binding. They also demonstrate the basis of differential activities among different ligands. In addition, unexpected interactions between MC1R and the G{beta} subunit were discovered from these structures. Together, our results provide a conserved mechanism of calcium-mediated ligand recognition, specific mode of G protein coupling, and a universal activation pathway of melanocortin receptors.

biophysics↗

bioRxiv2021

TMEM120A contains a specific coenzyme A-binding site and might not mediate poking- or stretch-induced channel activities in cells

TMEM120A, a member of the Transmembrane protein 120 (TMEM120) family, has pivotal function in adipocyte differentiation and metabolism, and may also contribute to sensing mechanical pain by functioning as an ion channel named TACAN. Here we report that expression of TMEM120A is not sufficient in mediating poking- or stretch-induced currents in cells, and have solved cryo-EM structures of human TMEM120A (HsTMEM120A) in complex with an endogenous metabolic cofactor (coenzyme A, CoASH) and in the apo form. HsTMEM120A forms a symmetrical homodimer with each monomer containing an amino-terminal coiled-coil motif followed by a transmembrane domain with six membrane-spanning helices. Within the transmembrane domain, a CoASH molecule is hosted in a deep cavity and forms specific interactions with nearby amino acid residues. Mutation of a central tryptophan residue involved in binding CoASH dramatically reduced the binding affinity of HsTMEM120A with CoASH. HsTMEM120A exhibits distinct conformations at the states with or without CoASH bound. Our results suggest that TMEM120A may have alternative functional roles potentially involved in CoASH transport, sensing or metabolism.

biophysics↗

bioRxiv2021

Sequencing uracil in DNA at single-nucleotide resolution

As an aberrant base in DNA, uracil is generated by dUMP misincorporation or cytosine deamination, and involved in multiple physiological and pathological processes. Current methods for whole-genome mapping of uracil all rely on uracil-DNA N-glycosylase (UNG) and are limited in resolution or specificity. Here, we present a UNG-independent Single-Nucleotide resolution Uracil Sequencing (SNU-seq) method utilizing the UdgX protein which specifically excises the uracil and forms a covalent bond with the resulting deoxyribose. SNU-seq was validated on synthetic DNA and applied to mammalian genomes. We found that the uracil content of pemetrexed-treated cells fluctuated along with DNA replication timing. We also accurately detected uracil introduced through cytosine deamination by the cytosine base editor (nCas9-APOBEC) and verified uracil occurrence in "WRC" motif within Activation-Induced Cytidine Deaminase (AID) hotspot regions in CSR-activated UNG -/- B cells.

biochemistry↗

bioRxiv2021

The Oncoprotein BCL6 Enables Cancer Cells to Evade Genotoxic Stress

Genotoxic agents remain the mainstay of cancer treatment. Unfortunately, the clinical benefits are often countered by a rapid tumor adaptive response. Here, we report that the oncoprotein B cell lymphoma 6 (BCL6) is a core component that confers tumor adaptive resistance to genotoxic stress. Multiple genotoxic agents promoted BCL6 transactivation, which was positively correlated with a weakened therapeutic efficacy and a worse clinical outcome. Mechanistically, we discovered that treatment with the genotoxic agent etoposide led to the transcriptional reprogramming of multiple pro-inflammatory cytokines, among which the interferon- and interferon-{gamma} responses were selectively and substantially enriched in resistant cells. Our results further revealed that the activation of interferon/signal transducer and activator of transcription 1 axis directly upregulated BCL6 expression. The increased expression of BCL6 further repressed the tumor suppressor PTEN and consequently enabled resistant cancer cell survival. Accordingly, targeted inhibition of BCL6 remarkably enhanced etoposide-triggered DNA damage and apoptosis both in vitro and in vivo. Our findings highlight the importance of BCL6 signaling in conquering tumor tolerance to genotoxic stress, further establishing a rationale for a combined approach with genotoxic agents and BCL6-targeted therapy.

cancer biology↗

bioRxiv2021

Genetic structure in patchy populations of a candidate foundation plant: a case study of Leymus chinensis (Poaceae) using genetic and clonal diversity

PREMISEThe distribution of genetic diversity on the landscape has critical ecological and evolutionary implications. This may be especially the case on a local scale for foundation plant species since they create and define ecological communities, contributing disproportionately to ecosystem function. METHODSWe examined the distribution of genetic diversity and clones, which we defined first as unique multi-locus genotypes (MLG), and then by grouping similar MLGs into multi-locus lineages (MLL). We used 186 markers from inter-simple sequence repeats (ISSR) across 358 ramets from 13 patches of the foundation grass Leymus chinensis. We examined the relationship between genetic and clonal diversities, their variation with patch-size, and the effect of the number of markers used to evaluate genetic diversity and structure in this species. RESULTSEvery ramet had a unique MLG. Almost all patches consisted of individuals belonging to a single MLL. We confirmed this with a clustering algorithm to group related genotypes. The predominance of a single lineage within each patch could be the result of the accumulation of somatic mutations, limited dispersal, some sexual reproduction with partners mainly restricted to the same patch, or a combination of all three. CONCLUSIONSWe found strong genetic structure among patches of L. chinensis. Consistent with previous work on the species, the clustering of similar genotypes within patches suggests that clonal reproduction combined with somatic mutation, limited dispersal, and some degree of sexual reproduction among neighbors causes individuals within a patch to be more closely related than among patches.

ecology↗

bioRxiv2021

Analysis of the Genetic Structure and Diversity of Upland Cotton Groups in Different Planting Areas Based on SNP Markers

Genetic diversity, kinship and population genetic structure analyses of Gossypium hirsutum germplasm can provide a better understanding of the origin and evolution of G. hirsutum biodiversity. In this study, 1313331 SNP molecular markers were used to construct a phylogenetic tree of each sample using MEGAX, to perform population structure analysis by ADMIXTURE software and principal component analysis (PCA) by EIGENSOFT software, and to estimate relatedness using SPAGeDi. ADMIXTURE software divided the experimental cotton population into 16 subgroups, and the Gossypium hirsutum samples could be roughly clustered according to source place, but there were some overlapping characteristics among samples. The experimental cotton population was divided into six groups according to source to calculate the genetic diversity index (H), and the obtained value (0.306) was close to that for germplasm collected by others in China. Cluster 4 had a relatively high genetic diversity level (0.390). The degrees of genetic differentiation within the experimental cotton population groups were low (the population differentiation indexes ranged from 0.02368 to 0.10664). The genetic distance among cotton accessions varied from 0.000332651 to 0.562664014, with an average of 0.25240429. The results of this study may provide a basis for mining elite alleles and using them for subsequent association analysis.

genomics↗

bioRxiv2021

Stratum Lacunosum-moleculare Interneurons of the Hippocampus Coordinate Memory Encoding and Retrieval

Encoding and retrieval of memory are two processes serving distinct biological purposes but operating in highly overlapping brain circuits. It is unclear how the two processes are coordinated in the same brain regions, especially in the hippocampal CA1 region where the two processes converge at the cellular level. Here we find that the neuron-derived neurotrophic factor (NDNF)-positive interneurons at stratum lacunosum-moleculare (SLM) in CA1 play opposite roles in memory encoding and retrieval. These interneurons show high activities in learning and low activities in recall. Increasing their activity facilitates learning but impairs recall. They inhibit the entorhinal- but dis-inhibit the CA3- inputs to CA1 pyramidal cells and thereby either suppress or elevate CA1 pyramidal cells activity depending on animals behavioral states. Thus, by coordinating entorhinal- and CA3- dual inputs to CA1, these SLM interneurons are key to switching the hippocampus between encoding and retrieval modes.

neuroscience↗

bioRxiv2021

Molecular recognition of an acyl-peptide hormone and activation of ghrelin receptor

Ghrelin, also called "the hunger hormone", is a gastric peptide hormone that regulates food intake, body weight, as well as taste sensation, reward cognition, learning and memory. One unique feature of ghrelin is its acylation, primarily with an octanoic acid, which is essential for its binding and activation of the ghrelin receptor, a G protein-coupled receptor. The multifaceted roles of ghrelin make ghrelin receptor a highly attractive drug target for growth retardation, obesity, and metabolic disorders. Here we present two cryo-electron microscopy structures of Gq-coupled ghrelin receptor bound to ghrelin and a synthetic agonist, GHRP-6. Analysis of these two structures reveals a unique binding pocket for the octanoyl group, which guides the correct positioning of the peptide to initiate the receptor activation. Together with mutational and functional data, our structures define the rules for recognition of the acylated peptide hormone and activation of ghrelin receptor, and provide structural templates to facilitate drug design targeting ghrelin receptor.

biophysics↗

bioRxiv2021

Screening of Botanical Drugs against SARS-CoV-2 Entry

An escalating pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is impacting global health. Specific treatment options for diseases caused by SARS-CoV-2 are largely lacking. Herein, we used a pseudotype virus (pv) bearing the SARS-CoV-2 S glycoprotein to screen a botanical drug library to identify an agent against SARS-CoV-2 entry. All the four hits, including angeloylgomisin O, schisandrin B, procyanidin, and oleanonic acid, were identified for effective inhibition of SARS-CoV-2 S pv entry in the micromolar range. A mechanistic study revealed that these four agents inhibit SARS-CoV-2 S pv entry by blocking S-mediated membrane fusion. Furthermore, angeloylgomisin O, schisandrin B, and oleanonic acid inhibited authentic SARS-CoV-2 with a high selective index (SI). We also showed that all the four hits could also inhibit the entry of pv of Middle East respiratory syndrome coronavirus (MERS-CoV) and newly emerged SARS-CoV-2 variants (D614G, K417N/E484K/N501Y/D614G). In drug combination studies performed in cellular antiviral assays, angeloylgomisin O and schisandrin B displayed synergistic effects in combination with remdesivir. These results indicated that angeloylgomisin O, schisandrin B, procyanidin, and oleanonic acid can inhibit SARS-CoV-2 and that they are potential therapeutic agents for COVID-19.

microbiology↗

bioRxiv2021

CamelliA-based simultaneous imaging of Ca2+ dynamics in subcellular compartments

As a universal second messenger, calcium (Ca2+) transmits specific cellular signals via a spatiotemporal signature generated from its extracellular source and internal stores. Our knowledge of the mechanisms underlying generation of a Ca2+ signature is hampered by limited tools enabling simultaneous monitoring of the dynamics of Ca2+ levels in multiple subcellular compartments. To overcome the limitation and to further improve spatiotemporal resolutions, here we have assembled a molecular toolset (the CamelliA lines) in Arabidopsis that enables simultaneous and high-resolution monitoring of Ca2+ dynamics in multiple subcellular compartments through imaging analyses of different single-colored GECIs (Genetically Encoded Calcium Indicators). Indeed, the uncovering of the previously unrecognized Ca2+ signatures in three types of Arabidopsis cells in response to internal and external cues is a testimony to the wide applicability of the newly generated toolset for elucidating the subcellular sources contributing to the Ca2+signatures in plants. One sentence summaryA toolset for simultaneous imaging of Ca2+ dynamics in subcellular compartments has uncovered unrecognized Ca2+ signatures in Arabidopsis cells in response to developmental and external cues.

plant biology↗

bioRxiv2021

Magnetic Resonance Spectroscopy Frequency and Phase Correction Using Convolutional Neural Networks

We introduce DeepSPEC, a novel convolutional neural network (CNN) -based approach for frequency-and-phase correction (FPC) of MRS spectra to achieve fast and accurate FPC of single-voxel PRESS MRS and MEGA-PRESS data. In DeepSPEC, two neural networks, including one for frequency correction and one for phase correction were trained and validated using published simulated and in vivo PRESS and MEGA-PRESS MRS dataset with wide-range artificial frequency and phase offsets applied. DeepSPEC was subsequently tested and compared to the current deep learning solution - a "vanilla" neural network approach using multilayer perceptrons (MLP). Furthermore, random noise was added to the original simulated dataset to further investigate the model performance with noise at varied signal-to-noise (SNR) levels (i.e., 6 dB, 3 dB, and 1.5 dB). The testing showed that DeepSPEC is more robust to noise compared to the MLP-based approach due to having a smaller absolute error in both frequency and phase offset prediction. The DeepSPEC framework was capable of correcting frequency offset with 0.01{+/-}0.01 Hz and phase offset with 0.12{+/-}0.09{degrees} absolute errors on average for unseen simulated data at a high SNR (12 dB) and correcting frequency offset with 0.01{+/-}0.02 Hz and phase offset within -0.07{+/-}0.44{degrees} absolute errors on average at very low SNR (1.5 dB). Furthermore, additional frequency and phase offsets (i.e., small, moderate, large) were applied to the in vivo dataset, and DeepSPEC demonstrated better performance for FPC when compared to the MLP-based approach. Results also show DeepSPEC has superior performance than the model-based SR implementation (mSR) in FPC by having higher accuracy in a wider range of additional offsets. These results represent a proof of concept for the use of CNNs for preprocessing MRS data and demonstrate that DeepSPEC accurately predicts frequency and phase offsets at varying noise levels with state-of-the-art performance.

neuroscience↗

bioRxiv2021

Somatic mutation involving activated signaling, transcription, or tumor suppression is a premise of MDS evolving into AML

The transformation biology of secondary AML from MDS is still not fully understood. Here, we performed a large cohort of paired sequences including target, whole-exome and single cell sequencing to search AML transformation-related mutations (TRM). The results showed that fifty-five out of the 64 (85.9%) patients presented presumptive TRM involving activated signaling, transcription factors, or tumor suppressors. Most of TRM (63.6%, 35 cases) emerged at the leukemia transformation point. All five of the remaining nine patients analyzed by paired whole exome sequencing showed TRM which are not included in the reference targets. Single-cell sequencing indicated that the activated cell signaling route was related to TRM which take place prior to phenotypic development. Of note, defined TRM was limited to a small set of genes (less than ten, in the order: NRAS/KRAS, CEBPA, TP53, FLT3, RUNX1, CBL, PTPN11 and WT1, accounted for 91.0% of the mutations). In conclusion, somatic mutations involving in activated signaling, transcription factors, or tumor suppressors appeared to be a precondition for AML transformation from myelodysplastic syndromes. The TRM may be considered as new therapy targets.

cancer biology↗

bioRxiv2021

Mechanistic insights into dideoxygenation in gentamicin biosynthesis

Gentamicin is an important aminoglycoside antibiotic used for treatment of infections caused by Gram-negative bacteria. Although most of the biosynthetic pathway of gentamicin has been elucidated, a remaining intriguing question is how the intermediates JI-20A and JI-20B undergo a dideoxygenation to form gentamicin C complex. Here we show that the dideoxygenation process starts with GenP-catalyzed phosphorylation of JI-20A and JI-20Ba. The phosphorylated products are converted to C1a and C2a by concerted actions of two PLP (pyridoxal 5-phosphate)-dependent enzymes: elimination of water and then phosphate by GenB3 and double bond migration by GenB4. Each of these reactions liberates an imine which hydrolyses to a ketone or aldehyde and is then re-aminated by GenB3 using an amino donor. Crystal structures of GenB3 and GenB4 have guided site-directed mutagenesis to reveal crucial residues for the enzymes functions. We propose catalytic mechanisms for GenB3 and GenB4, which shed new light on the already unrivalled catalytic versatility of PLP-dependent enzymes.

microbiology↗

bioRxiv2021

Identification of residues in Lassa virus glycoprotein 1 involved in receptor switch

Lassa virus (LASV) is an enveloped, negative-sense RNA virus that causes Lassa hemorrhagic fever, for which there are limited treatment options. Successful LASV entry requires the viral glycoprotein 1 (GP1) to undergo a receptor switch from its primary receptor alpha-dystroglycan (-DG) to its endosomal receptor lysosome-associated membrane protein 1 (LAMP1). A conserved histidine triad in LASV GP1 has been reported to be responsible for receptor switch. To test the hypothesis that other non-conserved residues also contribute to receptor switch, we constructed a series of GP1 mutant proteins and tested them for binding to LAMP1. Four residues, L84, K88, L107, and H170, were identified as critical for receptor switch. Substituting any of the four residues with the corresponding lymphocytic choriomeningitis virus residue (L84N, K88E, L10F, and H170S) reduced the binding affinity of GP1LASV for LAMP1. Moreover, all the mutations caused decreases in GPC-mediated membrane fusion at both pH 4.5 and 5.2. The infectivity of pseudotyped viruses bearing either GPCL84N or GPCK88E decreased sharply in multiple cell types, whereas L107F and H170S had only mild effects on infectivity. Notably, in LAMP1 knockout cells, all four mutants showed reduced pseudovirus infectivity. Using biolayer light interferometry assay, we found that all four mutants had decreased binding affinity to LAMP1, in the order L84N > L107F > K88E > H170S. IMPORTANCELassa virus requires pH-dependent receptor switch to infect host cells; however, the underlying molecular mechanisms of this process are not well known. Here, we identify four residues, L84, K88, L107, and H170 that contribute to the interaction with the second receptor lysosome-associated membrane protein 1 (LAMP1). Mutant any of the four residues would impair the binding affinity to LAMP1, decrease the glycoprotein mediated membrane fusion, and reduce the pseudovirus infectivity.

microbiology↗

bioRxiv2021

PLURIPOTENT STEM CELL-DERIVED CARDIOVASCULAR PROGENITORS DIFFFERENTIATED ON LAMININ 221 REGENERATE AND IMPROVE FUNCTION OF INFARCTED SWINE HEARTS

BackgroundIschemic heart disease is a huge global burden where patients often have irreversibly damaged heart muscle. State-of-the-art technology using stem cell-derived products for cellular therapy could potentially replace damaged heart muscle for regenerative cardiology. Methods and ResultsPluripotent human embryonic stem cells (hESCs) were differentiated on a laminin LN521+221 matrix to cardiovascular progenitors (CVPs). Global transcriptome analyses at multiple time points by single-cell RNA-sequencing demonstrated high reproducibility (R2 > 0.95) between two hESCs lines. We identified several CVP signature genes as quality batch control parameters which are highly specific to our CVPs as compared to canonical cardiac progenitor genes. A total of 200 million CVPs were injected into the infarcted region caused by permanent ligation of the coronary arteries of 10 immunosuppressed pigs and maintained for 4- and 12-weeks post transplantation. The transplanted cells engrafted and proliferated in the infarcted area as indicated by IVIS imaging, histology staining and spatial transcriptomic analysis. Spatial transcriptomic analysis at 1 week following transplantation showed that the infarcted region expressed human genes in the same area as immunohistology sections. Heart function was analyzed by magnetic resonance imaging (MRI) and computerized tomography (CT). Functional studies revealed overall improvement in left ventricular ejection fraction by 21.35 {+/-} 3.3 %, which was accompanied by significant improvements in ventricular wall thickness and wall motion, as well as a reduction in infarction size after CVP transplantation as compared to medium control pigs (P < 0.05). Immunohistology analysis revealed maturation of the CVPs to cardiomyocytes (CMs) where the human grafts aligned with host tissue forming end-to-end connections typical for heart muscle. Electrophysiology analyses revealed electric continuity between injected and host tissue CMs. Episodes of ventricular tachyarrhythmia (VT) over a period of 25 days developed in four pigs, one pig had persistent VT, while the rest remained in normal sinus rhythm. All ten pigs survived the experiment without any VT-related death. ConclusionsWe report a highly reproducible, chemically defined and fully humanized differentiation method of hESCs for the generation of potent CVPs. This method may pave the way for lasting stem cell therapy of myocardial infarction (MI) in humans. Clinical PerspectiveO_ST_ABSWhat is New?C_ST_ABSO_LIWe present a highly reproducible, chemically defined and fully humanized laminin-based differentiation method for generation of large amounts of cardiovascular progenitors (CVP); 20 million cells in a 10 cm2 culture dish which were used for a preclinical study in pigs. C_LIO_LITransplantation of the CVPs into the myocardial infarcted pig hearts yields maturation of the progenitor cells to cardiomyocytes (CMs) and improved cardiac function (21.35 {+/-} 3.3 % LVEF improvement) using only 200 million CVPs. C_LIO_LITemporary episodes of ventricular arrhythmia (50%) were observed after CVP transplantation. No fatal ventricular arrhythmia occurred. C_LI What are the clinical implications?O_LIOur laminin-based approach generated potent CVPs in vivo and largely restored function of the damaged heart. C_LIO_LICardiovascular progenitors may provide a new and safe therapeutic strategy for myocardial infarction. C_LIO_LIThe results may have a significant impact on regenerative cardiology. C_LI

cell biology↗

bioRxiv2021

The Expression of Angiopoietin-1 and -2 in the Osteogenesis of Mesenchymal Stem Cells

ObjectiveThe objectives of this study are to clarify whether rat bone marrow derived Mesenchymal stem cells (MSCs) express Ang1 and Ang2 and their expression in the process of osteogenesis in vitro. Material and MethodsMSCs were cultured from rat tibia bone marrow cells and the hemopoietic stem cells were deplete by consistently replacement of the culture medium. The MSCs were induced osteogenesis with mineralization conditional medium and Immunohistochemical and immunofluorescent staining were performed to assess the expression of Ang1 and Ang2. ResultsThe method used to expand rat MSCs in vitro was applicable, and the cell morphology is spindle-like shape that is consistent with the privous reports. The immunohistochemical staining results showed that both Ang1 and Ang2 were expressed by rat MSCs. Both Ang1 and Ang2 were up-regulated in the process of osteogenesis of rat MSCs. ConclusionRat MSCs express both Ang1 and Ang2 which might play critical roles in the osteogenesis in vitro.

cell biology↗

bioRxiv2021

Brain image-derived phenotypes yield insights into causal risk of psychiatric disorders using a Mendelian randomization study

Brain imaging-derived phenotypes (IDPs) serve as underlying functional intermediates in psychiatric disorders, both of which are highly polygenic and heritable. Observational studies have elucidated the correlation between IDPs and psychiatric disorders, yet no systematic screening of IDPs to confer the causal liability in such disorders. We conducted a bidirectional two-sample Mendelian randomization framework to explore the causality of 1,901 IDPs on 10 psychiatric disorders and established the BrainMR database (http://brainmr.online/idp2psy/Index.php). We identified 17 causalities in forward MR analyses and 14 causalities in reverse MR analyses, which all rigorously examined them through various sensitivity analyses. The top significant relationship in forward was a unit lower volume of right central lateral of the thalamic nuclei, which was causally associated with an increased anorexia nervosa risk with an estimated OR of 0.52 (95% CI 0.41-0.64, P = 3.32 x 10-9). In reverse, the top significant IDP to be affected was the area of superior segment of the circular sulcus of the insula in the right hemisphere, which was increased by the reason of SCZ risk with an estimated association effect size of 0.068 (95% CI 0.046-0.090, P = 1.12 x 10-6). Overall, our study provides unique insights into causal pathways of psychiatric disorders at the imaging levels.

neuroscience↗

bioRxiv2021

Predicting hosts based on early SARS-CoV-2 samples and analyzing later world-wide pandemic in 2020

The SARS-CoV-2 pandemic has raised the concern for identifying hosts of the virus since the early-stage outbreak. To address this problem, we proposed a deep learning method, DeepHoF, based on extracting the viral genomic features automatically, to predict host likelihood scores on five host types, including plant, germ, invertebrate, non-human vertebrate and human, for novel viruses. DeepHoF made up for the lack of an accurate tool applicable to any novel virus and overcame the limitation of the sequence similarity-based methods, reaching a satisfactory AUC of 0.987 on the five-classification. Additionally, to fill the gap in the efficient inference of host species for SARS-CoV-2 using existed tools, we conducted a deep analysis on the host likelihood profile calculated by DeepHoF. Using the isolates sequenced in the earliest stage of COVID-19, we inferred minks, bats, dogs and cats were potential hosts of SARS-CoV-2, while minks might be one of the most noteworthy hosts. Several genes of SARS-CoV-2 demonstrated their significance in determining the host range. Furthermore, the large-scale genome analysis, based on DeepHoFs computation for the later world-wide pandemic in 2020, disclosed the uniformity of host range among SARS-CoV-2 samples and the strong association of SARS-CoV-2 between humans and minks.

bioinformatics↗