Biology subjects

Tan, Y.

Publications and source records attributed to Tan, Y..

At least 181 records · Page 10Linked to original sources

bioRxiv2020

QueryFuse Is A Sensitive Algorithm For Detection Of Gene-Specific Fusions

Recurrent chromosomal translocations, known as fusions, play important roles in carcinogenesis. They can serve as valuable diagnostic and therapeutic targets. RNA-seq is an ideal platform for detecting transcribed fusions, and computational methods have been developed to identify fusion transcripts from RNA-seq data. However, some transciptome realignment procedures for these methods are unnecessary, making this task computationally expensive and time consuming. Therefore, we have developed QueryFuse, a novel hypothesis-based algorithm that identifies gene-specific fusion from pre-aligned RNA-seq data. It is designed to help biologists quickly find and/or computationally validate fusions of interest, together with visualization and detailed properties of supporting reads. By aligning reads to Query genes at the pre-processing step with a more sensitive, memory intensive local aligner, QueryFuse can reduce alignment time and improve detection sensitivity. QueryFuse performed better or at comparable levels with two popular tools (deFuse and TopHatFusion) on both simulated and well-annotated cell-line datasets. Finally, using QueryFuse, we identified a novel fusion event with a potential therapeutic implication in clinical samples. Taken together, our results showed that QueryFuse is efficient and reliable for detecting gene-specific fusion events.

bioinformatics↗

bioRxiv2020

Effective Assessments of a Short-duration Poor Posture on Upper Limb Muscle Fatigue before Physical Exercise

A forward head and rounded shoulder posture is a poor posture that is widely seen in everyday life. It is known that sitting in such a poor posture with long hours will bring health issues such as muscle pain. However, it is not known whether sitting in this poor posture for a short period of time will affect human activities. This paper investigates the effects of a shortduration poor posture before some typical physical activities such as push-ups. The experiments are set up as follows. Fourteen male subjects are asked to do push-ups until fatigue with two surface electromyography (sEMG) at the upper limb. Two days later, they are asked to sit in this poor posture for 15 mins with 8 sEMG sensors located at given back muscles. Then they do the push-ups after the short-duration poor posture. The observations from the median frequency of sEMG signals at the upper limb indicate that the short-duration poor posture does affect the fatigue procedure of push-ups. A significant decreasing trend of the performance of push-ups is obtained after sitting in this poor posture. Such effects indicate that some parts of the back muscles indeed get fatigued with only 15 minutes sitting in this poor posture. By further investigating the time-frequency components of sEMG of back muscles, it is observed that the low and middle frequencies of sEMG signals from the infraspinatus muscle of the dominant side are demonstrated to be more prone to fatigue with the poor posture. Although this study focuses only on push-ups, similar experiments can be arranged for other physical exercises as well. This study provides new insights into the effect of a short-duration poor posture before physical activities. These insights can be used to guide athletes to pay attention to postures before physical activities to improve performance and reduce the risk of injury.

bioinformatics↗

bioRxiv2020

Precision engineering of the transcription factor Cre1 in Hypocrea jecorina (Trichoderma reesei) for efficient cellulase production in the presence of glucose

In Trichoderma reesei, carbon catabolite repression (CCR) significantly downregulates the transcription of cellulolytic enzymes, which is usually mediated by the zinc finger protein Cre1. It was found that there is a conserved region at the C-terminus of Cre1/CreA in several cellulase-producing fungi that contains up to three continuous S/T phosphorylation sites. Here, S387, S388, T389, and T390 at the C-terminus of Cre1 in T. reesei were mutated to valine for mimicking an unphosphorylated state, thereby generating the transformants Tr_Cre1S387V, Tr_Cre1S388V, Tr_Cre1T389V, and Tr_Cre1T390V, respectively. Transcription of cel7a in Tr_ Cre1S388V was markedly higher than that of the parent strain when grown in glucose-containing media. Under these conditions, both filter paperase (FPase) and p-nitrophenyl-{beta}-D-cellobioside (pNPCase) activities, as well as soluble proteins from Tr_Cre1S388V were significantly increased by up to 2- to 3-fold compared with that of other transformants and the parent strain. To our knowledge, this is the first report demonstrating an improvement of cellulase production in fungal species under CCR by mimicking dephosphorylation at the C-terminus of Cre1. Taken together, we developed a precision engineering strategy based on the modification of phosphorylation sites of Cre1 transcription factor to enhance the production of cellulase in fungal species under CCR.

bioengineering↗

bioRxiv2020

Novel Immunoglobulin Domain Proteins Provide Insights into Evolution and Pathogenesis Mechanisms of SARS-Related Coronaviruses

A novel coronavirus (SARS-CoV-2) is the causative agent of an emergent severe respiratory disease (COVID-19) in humans that is threatening to result in a global health crisis. By using genomic, sequence, structural and evolutionary analysis, we show that Alpha- and Beta-CoVs possess several novel families of immunoglobulin (Ig) domain proteins, including ORF8 and ORF7a from SARS-related coronaviruses and two protein groups from certain Alpha-CoVs. Among them, ORF8 is distinguished in being rapidly evolving, possessing a unique insert and a hypervariable position among SARS-CoV-2 genomes in its predicted ligand-binding groove. We also uncover many Ig proteins from several metazoan viruses which are distinct in sequence and structure but share an architecture comparable to that of CoV Ig domain proteins. Hence, we propose that deployment of Ig domain proteins is a widely-used strategy by viruses, and SARS-CoV-2 ORF8 is a potential pathogenicity factor which evolves rapidly to counter the immune response and facilitate the transmission between hosts.

microbiology↗

bioRxiv2020

Comparison of the two up-to-date sequencing technologies for genome assembly: HiFi reads of Pacbio Sequel II system and ultralong reads of Oxford Nanopore

The availability of reference genomes has revolutionized the study of biology. Multiple competing technologies have been developed to improve the quality and robustness of genome assemblies during the last decade. The two widely-used long read sequencing providers - Pacbio (PB) and Oxford Nanopore Technologies (ONT) - have recently updated their platforms: PB enable high throughput HiFi reads with base-level resolution with >99% and ONT generated reads as long as 2 Mb. We applied the two up-to-date platforms to one single rice individual, and then compared the two assemblies to investigate the advantages and limitations of each. The results showed that ONT ultralong reads delivered higher contiguity producing a total of 18 contigs of which 10 were assembled into a single chromosome compared to that of 394 contigs and three chromosome-level contigs for the PB assembly. The ONT ultralong reads also prevented assembly errors caused by long repetitive regions for which we observed a total 44 genes of false redundancies and 10 genes of false losses in the PB assembly leading to over/under-estimations of the gene families in those long repetitive regions. We also noted that the PB HiFi reads generated assemblies with considerably less errors at the level of single nucleotide and small InDels than that of the ONT assembly which generated an average 1.06 errors per Kb assembly and finally engendered 1,475 incorrect gene annotations via altered or truncated protein predictions.

genomics↗

bioRxiv2020

DPSN: standardizing the short names of amplicon-sequencing primers to avoid ambiguity

BackgroundAmplicon sequencing is the most widely used sequencing method to evaluate microbial diversity in virtually all environments. Thus, appropriate and specific primers are needed to amplify amplicon regions in amplicon sequencing. For this purpose, the community currently uses probeBase, which curates rRNA-targeted probes and primers. Main BodyWe found that 63.58% of the primers in probeBase have problematic issues in the short name, full name, and/or position. Furthermore, the current convention for short names causes ambiguity. We here introduce our new Database of Primer Scientific Names (DPSN), which is a manually curated database for the 173 primers in probeBase complete with a new short name convention. Building on the work of probeBase, we provide a more user-friendly and standardized system. The new short primer naming convention has three basic components: 5{square} position on the sense strand, version, and direction. An additional character for the name of the taxonomic group is also added in front of the name for convenient use. Furthermore, DPSN contains primers for large subunit as well. In order to separate them from the primers for small subunit, a header character is also recommended. ConclusionAll 173 primers in probeBase were corrected according to this new rule, and are stored in DPSN, which is expected to facilitate accurate primer selection and better standardized communication in this field. Database URLThe DPSN database is available in a user-interactive website at http://dpsn.leidailab.cn/

microbiology↗

bioRxiv2020

Improved subspecies identification in clinical Mycobacterium abscessus complex isolates using whole genome sequence

Mycobacterium abscessus complex, which is frequently reported causing a variety of skin and soft tissues diseases in humans, is composed of three subspecies, namely M. abscessus subsp. abscessus, M. abscessus subsp. massiliense and M. abscessus subsp. bolletii. Currently, the differentiation of these three subspecies in clinical isolates still largely depend on single gene identification methods like the genes namely hsp65, 16s with a limited accuracy. This study confirmed the limitations of the single gene based method in the subspecies identification. We performed a comprehensive analysis of MABC genomes in the NCBI database and tried to build an accurate and user-friendly identify method. Here, we describe an improved assay for Mycobacterium abscessus complex fast identification using WGS data, based on the identities of rpoB, erm(41) and rpls. Comprehensive analysis has been performed to compare our software results with the traditional method. The result showed that the method built-in this study could 100% identification the subspecies for the Mycobacterium abscessus complex in the public genome database (893 genomes from NCBI database and 6 clinical isolates from this study). Because this software can be easily integrated into a routine workflow to quickly and precisely provide subspecies-level identification and discrimination MABC different subspecies in clinical isolates by WGS. This assay will facilitate accurate molecular identification of species from the MABC complex in a variety of clinical specimens and diagnostic contexts.

microbiology↗

bioRxiv2019

Predominance of positive epistasis among drug resistance-associated mutations in HIV-1 protease

Drug-resistant mutations often have deleterious impacts on replication fitness, posing a fitness cost that can only be overcome by compensatory mutations. However, the role of fitness cost in the evolution of drug resistance has often been overlooked in clinical studies or in vitro selection experiments, as these observations only capture the outcome of drug selection. In this study, we systematically profile the fitness landscape of resistance-associated sites in HIV-1 protease using deep mutational scanning. We construct a mutant library covering combinations of mutations at 11 sites in HIV-1 protease, all of which are associated with resistance to protease inhibitors in clinic. Using deep sequencing, we quantify the fitness of thousands of HIV-1 protease mutants after multiple cycles of replication in human T cells. Although the majority of resistance-associated mutations have deleterious effects on viral replication, we find that epistasis among resistance-associated mutations is predominantly positive. Furthermore, our fitness data are consistent with genetic interactions inferred directly from HIV sequence data of patients. Fitness valleys formed by strong positive epistasis reduce the likelihood of reversal of drug resistance mutations. Overall, our results support the view that strong compensatory effects are involved in the emergence of clinically observed resistance mutations and provide insights to understanding fitness barriers in the evolution and reversion of drug resistance.

evolutionary biology↗

bioRxiv2019

Phylogeographic and phylodynamic approaches to epidemiological hypothesis testing

Computational analyses of pathogen genomes are increasingly used to unravel the dispersal history and transmission dynamics of epidemics. Here, we show how to go beyond historical reconstructions and use spatially-explicit phylogeographic and phylodynamic approaches to formally test epidemiological hypotheses. We illustrate our approach by focusing on the West Nile virus (WNV) spread in North America that has been responsible for substantial impacts on public, veterinary, and wildlife health. WNV isolates have been sampled at various times and locations across North America since its introduction to New York twenty years ago. We exploit this genetic data repository to demonstrate that factors hypothesised to affect viral dispersal and demography can be formally tested. Specifically, we detail and apply an analytical workflow consisting of state-of-the art methods that we further improve to test the impact of environmental factors on the dispersal locations, velocity, and frequency of viral lineages, as well as on the genetic diversity of the viral population through time. We find that WNV lineages tend to disperse faster in areas with higher temperatures and we identify temporal variation in temperature as a main predictor of viral genetic diversity through time. Using a simulation procedure, we find no evidence that viral lineages preferentially circulate within the same migratory bird flyway, suggesting a substantial role for non-migratory birds or mosquito dispersal along the longitudinal gradient. Finally, we also separately apply our testing approaches on the three WNV genotypes that circulated in North America in order to understand and compare their dispersal ability. Our study demonstrates that the development and application of statistical approaches, coupled with comprehensive pathogen genomic data, can address epidemiological questions that might otherwise be difficult or impractically expensive to answer.

evolutionary biology↗

bioRxiv2019

TAL1-mediated epigenetic modifications down-regulate the expression of GIMAP family in non-small cell lung cancer

BackgroudThe study was designed to explore the role of GIMAP family in non-small cell lung cancer (NSCLC) and its possible expression regulation mechanisms using existing biological databases including encyclopedia of DNA elements (ENCODE), gene expression omnibus (GEO), and the cancer genome atlas (TCGA).\n\nMethodsLung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) were used to evaluate the expression of GIMAPs in TCGA. Five NSCLC datasets were then selected from GEO for validation. RNA-seq and Chip-seq data from ENCODE and GEO were used to observe epigenetic modifications on the chromosomes of GIAMPs in NSCLC. We constructed protein-protein interaction (PPI) network to reveal the main interacting proteins of GIMAPs. We then analyzed the correlation and regulatory mechanism between TAL1 and the expression of GIMAP family. We also used Kaplan-Meier for survival analysis.\n\nResultsAll 7 genes in the GIMAP family were down-regulated in NSCLC. H3K4me3 and H3K27ac disappeared, while H3K27me3 increased on the chromosome of this family. The expression of TAL1 was positively correlated with the expression of GIMAPs. sh-TAL1 significantly down-regulated the expression of GIMAP family through epigenetic modification. High expression of GIMAPs and TAL1 was found to be associated with a good prognosis of NLCSC.\n\nConclusionThe downregulation of TAL1 caused the disappearance of H3K27ac and H3K4me3. It also caused an increase in H3K27me3 on the GIMAPs gene, eventually leading to the overall downregulation of the GIMAP family genes.

bioinformatics↗

bioRxiv2019

Characterization of Mucosal Dysbiosis of Early Colonic Neoplasia

Aberrant crypt foci (ACF) are the earliest morphologically identifiable lesion in the colon that can be detected by high-definition chromoendoscopy with contrast dye-spray. Although frequently associated with synchronous adenomas, their role in colorectal tumor development, particularly in the proximal colon, is still not clear. The goal of this study was to evaluate the profile of colon-associated bacteria associated with proximal ACF and to investigate their relationship to the presence and subtype of synchronous polyps present throughout the colon. Forty-five subjects undergoing a screening or surveillance colonoscopy were included in this retrospective study. Our study cohort included a total of 16 subjects with no identifiable proximal lesions (either ACF or polyp), 14 subjects with at least 1 ACF but no polyp(s), and 15 subjects with both at least 1 ACF and a synchronous proximal polyp(s) detected at colonoscopy. Bacterial cells adherent to the epithelia of ACF and normal mucosa were visualized by in situ hybridization within confocal sections. Bacterial DNA isolated from biopsies was used to construct PCR amplicon libraries targeting the V4 hypervariable region of the 16S rRNA gene, which were then sequenced on the Illumina platform. ACF showed significantly greater heterogeneity in their bacterial profiles compared to normal mucosa. Interestingly, one of the bacterial community structures we characterized was strongly correlated with the presence of synchronous polyps. The observed dysbiosis is more prominent within the colonic epithelium that also harbors synchronous polyps. Finally using DNA-mass spectrometry to evaluate a panel of colorectal cancer hot-spot mutations present in the ACF, we found that several APC gene mutations (R1450*, R876*, S1465fs*3) were positively associated with the presence of Instestinibacter sp., whereas KRAS mutations (G12V, G12D) were positively correlated with Ruminococcus gnavus. This result indicates a potential relationship between specific colon-associated bacterial species and somatically acquired CRC-related mutations. Overall, our findings suggest that perturbations to the normal adherent mucosal flora may constitute a risk factor for early neoplasia, demonstrating the potential impact of mucosal dysbiosis on the tissue microenvironment and behavior of ACF that may facilitate (or impede) their progression towards more advanced forms of neoplasia.

microbiology↗

bioRxiv2019

CNOT1 mediates phosphorylation via Protein kinase A on the circadian clock

At the core of the mammalian circadian feedback loop, CLOCK (NPAS2)-BMAL1 is the positive element to activate transcription of downstream genes encoding the negative elements PERs and CRYs. Here we show that CNOT1 associates with both CLOCK and BMAL1, promotes their phosphorylation and increases their protein stability, and in turn inhibits the transcriptional activity of CLOCK-BMAL1. Expression of either CLOCK, BMAL1 or CNOT1 could interact with endogenous Protein Kinase A (PKA) as assessed by co-immunoprecipitation (Co-IP) and kinase assays. PKA could phosphorylate CLOCK and BMAL1 and this was promoted by CNOT1. Genetic deletion of PKA-C by CRISPR-Cas9 results in a longer period of the circadian rhythm; while overexpression of PKA-C induces a shorter period. Furthermore, we demonstrate that CNOT1 associates with CLOCK and BMAL1 in the mouse liver and promotes their phosphorylation. PER2, but not CRY2, is also a PKA target. Our results suggest that CNOT1 and PKA play a critical role in the mammalian circadian clock, revealing a conserved function in eukaryotic circadian regulations.

developmental biology↗

bioRxiv2019

Conjugated linolenic fatty acids trigger ferroptosis in triple-negative breast cancer

Ferroptosis is a non-apoptotic form of cell death linked to the accumulation of reactive hydroperoxides generated by oxidation of polyunsaturated fatty acids (PUFAs) in membrane phospholipids. The therapeutic potential of promoting ferroptosis by enriching PUFAs in cancer cells is unknown. We found an association between elevated PUFA levels and vulnerability to ferroptosis in triple-negative breast cancer (TNBC) cells. A screen of PUFAs identified conjugated linolenic acids, including -eleostearate, as ferroptosis inducers. Three conjugated double bonds were required for ferroptotic activity although their positioning and stereochemistry were less significant. Mechanistically, -eleostearate differed from canonical ferroptosis inducers by a distinct dependence on acyl-CoA synthetase long-chain isoforms and by not altering glutathione or glutathione peroxidase 4 activity. Orally administered tung oil, naturally rich in -eleostearate, limited tumor growth and metastasis in an aggressive TNBC xenograft model. These results expand our understanding of ferroptotic cell death and highlight the anti-cancer potential of conjugated PUFAs.

cancer biology↗

bioRxiv2019

Global Signal Regression Strengthens Association between Resting-State Functional Connectivity and Behavior

Global signal regression (GSR) is one of the most debated preprocessing strategies for resting-state functional MRI. GSR effectively removes global artifacts driven by motion and respiration, but also discards globally distributed neural information and introduces negative correlations between certain brain regions. The vast majority of previous studies have focused on the effectiveness of GSR in removing imaging artifacts, as well as its potential biases. Given the growing interest in functional connectivity fingerprinting, here we considered the utilitarian question of whether GSR strengthens or weakens associations between resting-state functional connectivity (RSFC) and multiple behavioral measures across cognition, personality and emotion. By applying the variance component model to the Brain Genomics Superstruct Project (GSP), we found that behavioral variance explained by whole-brain RSFC increased by an average of 47% across 23 behavioral measures after GSR. In the Human Connectome Project (HCP), we found that behavioral variance explained by whole-brain RSFC increased by an average of 40% across 58 behavioral measures, when GSR was applied after ICA-FIX de-noising. To ensure generalizability, we repeated our analyses using kernel regression. GSR improved behavioral prediction accuracies by an average of 64% and 12% in the GSP and HCP datasets respectively. Importantly, the results were consistent across methods. A behavioral measure with greater RSFC-explained variance (using the variance component model) also exhibited greater prediction accuracy (using kernel regression). A behavioral measure with greater improvement in behavioral variance explained after GSR (using the variance component model) also enjoyed greater improvement in prediction accuracy after GSR (using kernel regression). Furthermore, GSR appeared to benefit task performance measures more than self-reported measures. Since GSR was more effective at removing motion-related and respiratory-related artifacts, GSR-related increases in variance explained and prediction accuracies were unlikely the result of motion-related or respiratory-related artifacts. However, it is worth emphasizing that the current study focused on whole-brain RSFC, so it remains unclear whether GSR improves RSFC-behavioral associations for specific connections or networks. Overall, our results suggest that at least in the case for young healthy adults, GSR strengthens the associations between RSFC and most (although not all) behavioral measures. Code for the variance component model and ridge regression can be found here: https://github.com/ThomasYeoLab/CBIG/tree/master/stable_projects/preprocessing/Li2019_GSR. HighlightsO_LIGlobal signal regression improves RSFC-behavior associations C_LIO_LIGlobal signal regression improves RSFC-based behavioral prediction accuracies C_LIO_LIImprovements replicated across two large-scale datasets and methods C_LIO_LITask-performance measures enjoyed greater improvements than self-reported ones C_LIO_LIGSR beneficial even after ICA-FIX C_LI

neuroscience↗

bioRxiv2019

Loss of a glutaredoxin gene underlies parallel evolution of trichome patter in Antirrhinum

Most angiosperms produce trichomes--epidermal hairs that have protective or more specialised roles. In almost all species trichomes are multicellular and, in the majority, secretory. Despite the importance of multicellular trichomes for plant protection and as a source of high-value products, little is known about the mechanisms that control their development. Here we use natural variation between Antirrhinum (snapdragon) species to examine how trichome distribution is regulated and has evolved. We show that a single gene, Hairy (H), which is needed to repress trichome fate, underlies variation in trichome distribution patterns between all Antirrhinum species except one. H encodes an epidermis-specific glutaredoxin and trichome distribution within individual plants reflects the location of H expression. Gene phylogenies and functional tests suggest that H gained its trichome-repressing role late in eudicot evolution and that Antirrhinum species with widespread trichomes evolved multiple times from a largely bald ancestor though independent losses of H activity. We also find evidence for an evolutionary reversal involving a suppressor mutation, and for a pleiotropic effect of H that might constrain the evolution of trichome patterns.

plant biology↗

bioRxiv2018

SingleCellNet: a computational tool to classify single cell RNA-Seq data across platforms and across species

Single cell RNA-Seq has emerged as a powerful tool in diverse applications, ranging from determining the cell-type composition of tissues to uncovering the regulators of developmental programs. A near-universal step in the analysis of single cell RNA-Seq data is to hypothesize the identity of each cell. Often, this is achieved by finding cells that express combinations of marker genes that had previously been implicated as being cell-type specific, an approach that is not quantitative and does not explicitly take advantage of other single cell RNA-Seq studies. Here, we describe our tool, SingleCellNet, which addresses these issues and enables the classification of query single cell RNA-Seq data in comparison to reference single cell RNA-Seq data. SingleCellNet compares favorably to other methods, and it is notably able to make sensitive and accurate classifications across platforms and species. We demonstrate how SingleCellNet can be used to classify previously undetermined cells, and how it can be used to assess the outcome of cell fate engineering experiments.\n\nHighlightO_LISingleCellNet (SCN) enables the classification of scRNA-Seq data across platforms and species\nC_LIO_LISCN is open source and extendible\nC_LIO_LIWe illustrate the utility of SCN with three example applications\nC_LI\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=161 SRC=\"FIGDIR/small/508085_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (47K):\norg.highwire.dtl.DTLVardef@1750006org.highwire.dtl.DTLVardef@548dbdorg.highwire.dtl.DTLVardef@1257cb1org.highwire.dtl.DTLVardef@1d8072_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2018

TSD: A computational tool to study the complex structural variants using PacBio targeted sequencing data

The PacBio sequencing is a powerful approach to study the DNA or RNA sequences in a longer scope. It is especially useful in exploring the complex structural variants generated by random integration or multiple rearrangement of internal or external sequences. However, there is still no tool designed to uncover their structural organization in the host genome. Here, we present a tool, TSD, for complex structural variant discovery using PacBio targeted sequencing data. It allows researchers to identify and visualize the genomic structures of targeted sequences by unlimited splitting, alignment and assembly of long PacBio reads. Application to the sequencing data derived from an HBV integrated human cell line(PLC/PRF/5) indicated that TSD could recover the full profile of HBV integration events, especially for the regions with the complex human-HBV genome integrations and multiple HBV rearrangements. Compared to other long read analysis tools, TSD showed a better performance for detecting complex genomic structural variants. TSD is publicly available at: https://github.com/menggf/tsd

bioinformatics↗

bioRxiv2018

Homologous recombination shapes the genetic diversity and drives the evolution of African swine fever viruses

Recent outbreaks of African swine fever virus (ASFV) in China severely influenced the swine industry of the country. Currently, there is no effective vaccine or drugs against ASFVs. How to effectively control the virus is challenging. In this study, we have analyzed all the publicly available ASFV genomes and demonstrated that there was a large genetic diversity of ASFV genomes. Interestingly, the genetic diversity was mainly caused by extensive genomic insertions and/or deletions (indels) instead of the point mutations. The genomic diversity of the virus resulted in proteome diversity. Over 250 types of proteins were inferred from the ASFV genomes, among which only 144 were observed in all analyzed viruses. Further analyses showed that the homologous recombination may contribute much to the indels, as supported by significant associations between the occurrence of extensive recombination events and the indels in the ASFV genomes. Repeated elements of dozens of nucleotides in length were observed to widely distribute and cluster in the adjacent positions of ASFV genomes, which may facilitate the occurrence of homologous recombination. Moreover, two enzymes, which were possibly related to the homologous recombination, i.e., a Lambda-like exonuclease with a YqaJ-like viral recombinase domain, and a DNA topoisomerase II, were found to be conservative in all the analyzed ASFVs. This work highlighted the importance of the homologous recombination in the evolution of the ASFVs, and helped with the strategy development of the prevention and control of the virus.

microbiology↗