Biology subjects

Liao, H.

Publications and source records attributed to Liao, H..

At least 37 records · Page 2Linked to original sources

bioRxiv2024

Bacterial stress granule protects mRNA through ribonucleases exclusion

Membraneless droplets formed through liquid-liquid phase separation of ribonucleoprotein particles contribute to mRNA storage in eukaryotic cells. How such aggresomes contribute to mRNA dynamics under stress, and their functional role, is less understood in bacteria. Here we used multiple approaches including live-cell imaging, polymer physics modelling and transcriptomics to show that prolonged stress leading to ATP depletion in Escherichia coli results in increased aggresome formation, compaction, and selective mRNA enrichment within these aggresomes. Longer transcripts accumulate more in aggresomes than in the cytosol. Mass spectrometry and mutagenesis studies showed that mRNA ribonucleases are excluded from aggresomes due to electrostatic repulsion arising from their negative surface charges. Experiments with fluorescent reporters and disruption of aggresome formation showed that mRNA storage within aggresomes promoted rapid translation reactivation and associated with reduced lag phases during growth after stress removal. Our findings suggest that mRNA storage within aggresomes confers an advantage for bacterial survival and recovery from stress.

biophysics↗

bioRxiv2024

Accelerating de novo SINE annotation in plant and animal genomes

Genome annotation is an important but challenging task. Accurate identification of short interspersed nuclear elements (SINEs) is particularly difficult due to their lack of highly conserved sequences. AnnoSINE is state-of-the-art software for annotating SINEs in plant genomes, but its homology-based module is not available for animals and it is computationally inefficient for large genomes. Therefore, we propose AnnoSINE_v2, which extends accurate SINE annotation for animal genomes with greatly optimized computational efficiency. Our results show that AnnoSINE_v2s annotation of SINEs has over 20% higher F1-score compared to the existing tools on animal genomes and enables the processing of complicated genomes, like human and zebrafish, which were beyond the capabilities of AnnoSINE_v1. AnnoSINE_v2 is freely available on Conda and GitHub: https://github.com/liaoherui/AnnoSINE_v2.

bioinformatics↗

bioRxiv2024

Cryo-EM structures of human cone visual pigments

Trichromatic color vision in humans constitutes a pivotal evolutionary adaptation, endowing individuals with the capacity to discern and discriminate a diverse spectrum of colors. This unique visual capability confers a selective advantage crucial for successful adaptation, survival, and reproductive success in the natural environment. Color vision in humans is facilitated by the red, green, and blue cone visual pigments within cone photoreceptor cells. These pigments consist of a G-protein-coupled receptor opsin apoprotein and a chromophore covalently linked to opsins. Despite the elucidated structure of rhodopsin, the structures of cone visual pigments have yet to be determined. Here, we present the cryo-EM structures of three human cone visual pigments in complex with G proteins. Our structural analysis reveals detailed interactions between cone opsins, all-trans-retinal, and G proteins, indicating their active state. We also provide a concise summary and analysis of mutations in human cone opsins, elucidating potential relationships between residue substitutions and spectral tuning. Notably, S1162.67Y, A2335.52S, Y2776.44F were found to induce a blue shift in the absorption spectrum of the red-pigment, while the substitutions W2816.48Y and K3127.43A resulted in the absence of the absorption spectrum. The structural elucidation of human cone visual pigments significantly contributes to our understanding of how distinct types of cone cells perceive light across varying wavelengths. Furthermore, it provides a deeper insight into the functioning of the human trichromatic vision system, probing the mechanisms enabling humans to perceive a broad spectrum of colors.

biophysics↗

bioRxiv2023

A shift in the host web occupancy of dew-drop spiders associated with genetic divergence in the Southwest Pacific

AimWe assessed the population genetic structure of the kleptoparasitic spider Argyrodes bonadea across the Southwestern Pacific islands. Our focus is on assessing the impact of overseas distances and, in particular, the Kerama gap, as potential drivers of genetic differentiation. We found that the spider kleptoparasites switch to a specific host species is associated with significant genetic variation at fine scales, whereas the same species adoption of a generalist host strategy has likely facilitated its broad dispersal, colonization, and recent range expansion across the southwestern Pacific, and is associated with a lack of geographically- structured genetic variation in these latter, subsequently-colonized landmasses. LocationSouthwestern Pacific Islands TaxonArgyrodes bonadea MethodsWe used mitochondrial Cytochrome Oxidase 1 (CO1) gene sequences, and Restriction Site-associated DNA Sequencing (RAD-seq) for our analyses. ResultsTwo strongly supported lineages, an Amami-Okinawa Lineage (AOL) and an Austral-Asia Lineage (AAL) correspond to two separate clades, roughly divided by the Kerama Gap, in phylogenetic trees estimated here. However, species delimitation led to the interpretation of only a single species present. The AOL exhibits complex, geographically-structured host web spider species specificity, wherein the Amami population utilizes Cyrtophora, but AOL samples in Okinawa associates exclusively with Nephila--and yet all broadly distributed AAL populations show no evidence of host web spider species specificity. Main conclusionThe population boundary between AOL and AAL likely results from local adaptation to novel hosts--instead of isolation by the Kerama Gap--following long-distance dispersal and range expansion. Our results suggest kleptoparasitic spiders have the capacity to overcome permanent deep-sea barriers and colonize distant landmasses. Whereas peripheral populations (AOL) demonstrate the capacity for specialization to a single host, which may have contributed to genetic differentiation and isolation, the broadly-distributed AAL persists and has successfully expanded its geographical range as a host generalist, which may contribute to ongoing gene flow inferred in this study.

evolutionary biology↗

bioRxiv2023

Interferon-α promotes neo-antigen formation andpreferential HLA-B-restricted antigen presentation in pancreatic β-cells

Interferon (IFN)- is the earliest cytokine signature observed in individuals at risk for type 1 diabetes (T1D), but its effect on the repertoire of HLA Class I (HLA-I)-bound peptides presented by pancreatic {beta}-cells is unknown. Using immunopeptidomics, we characterized the peptide/HLA-I presentation in in-vitro resting and IFN--exposed {beta}-cells. IFN- increased HLA-I expression and peptide presentation, including neo-sequences derived from alternative mRNA splicing, post-translational modifications - notably glutathionylation - and protein cis-splicing. This antigenic landscape relied on processing by both the constitutive and immune proteasome. The resting {beta}-cell immunopeptidome was dominated by HLA-A-restricted ligands. However, IFN- only marginally upregulated HLA-A and largely favored HLA-B, translating into a major increase in HLA-B-restricted peptides and into an increased activation of HLA-B-restricted vs. HLA-A-restricted CD8+ T-cells. A preferential HLA-B hyper-expression was also observed in the islets of T1D vs. non-diabetic donors, and we identified islet-infiltrating CD8+ T-cells from T1D donors reactive to HLA-B-restricted granule peptides. Thus, the inflammatory milieu of insulitis may skew the autoimmune response toward epitopes presented by HLA-B, hence recruiting a distinct T-cell repertoire that may be relevant to T1D pathogenesis.

immunology↗

bioRxiv2023

A molecular proximity sensor based on an engineered, dual-component guide RNA

One of the goals of synthetic biology is to enable the design of arbitrary molecular circuits with programmable inputs and outputs. Such circuits bridge the properties of electronic and natural circuits, processing information in a predictable manner within living cells. Genome editing is a potentially powerful component of synthetic molecular circuits, whether for modulating the expression of a target gene or for stably recording information to genomic DNA. However, programming molecular events such as protein-protein interactions or induced proximity as triggers for genome editing remains challenging. Here we demonstrate a strategy termed "P3 editing", which links protein-protein proximity to the formation of a functional CRISPR-Cas9 dual-component guide RNA. By engineering the crRNA:tracrRNA interaction, we demonstrate that various known protein-protein interactions, as well as the chemically-induced dimerization of protein domains, can be used to activate prime editing or base editing in human cells. Additionally, we explore how P3 editing can incorporate outputs from ADAR-based RNA sensors, potentially allowing specific RNAs to induce specific genome edits within a larger circuit. Our strategy enhances the controllability of CRISPR-based genome editing, facilitating its use in synthetic molecular circuits deployed in living cells.

synthetic biology↗

bioRxiv2023

GDmicro: classifying host disease status with GCN and Deep adaptation network based on the human gut microbiome data

MotivationWith advances in metagenomic sequencing technologies, there are accumulating studies revealing the associations between the human gut microbiome and some human diseases. These associations shed light on using gut microbiome data to distinguish case and control samples of a specific disease, which is also called host disease status classification. Importantly, using learning-based models to distinguish the disease and control samples is expected to identify important biomarkers more accurately than abundance-based statistical analysis. However, available tools have not fully addressed two challenges associated with this task: limited labeled microbiome data and decreased accuracy in cross-studies. The confounding factors such as the diet, technical biases in sample collection/sequencing across different studies/cohorts often jeopardize the generalization of the learning model. ResultsTo address these challenges, we develop a new tool GDmicro, which combines semi-supervised learning and domain adaptation to achieve a more generalized model using limited labeled samples. We evaluated GDmicro on human gut microbiome data from 10 cohorts covering 5 different diseases. The results show that GDmicro has better performance and robustness than state-of-the-art tools. In particular, it improves the AUC from 0.783 to 0.949 in identifying inflammatory bowel disease. Furthermore, GDmicro can identify potential biomarkers with greater accuracy than abundance-based statistical analysis methods. It also reveals the contribution of these biomarkers to the hosts disease status. Availability and implementationhttps://github.com/liaoherui/GDmicro Contactyannisun@cityu.edu.hk Supplementary informationSupplementary data are available at XXX online

bioinformatics↗

bioRxiv2023

Microsporidia dressing up: the spore polaroplast transport through the polar tube and transformation into the sporoplasm membrane

Microsporidia are obligate intracellular parasites that infect a wide variety of hosts, including humans. Microsporidian spores possess a unique, highly specialized invasion apparatus involving the polar filament, polaroplast and posterior vacuole. During spore germination, the polar filament is discharged out of the spore forming the hollow polar tube that transports the sporoplasm components including nucleus into the host cell to achieve the invasion. Due to the complicated topological changes occurring in this process, the formation of sporoplasm is unclear. Here, electron microscopy observation and DiI staining confirmed that during spore germination, a large number of vesicles derived from the polaroplast, nucleus and other cytoplasm were transported out via the polar tube. Meanwhile, the posterior vacuole and plasma membrane remained in the empty spore coat. In addition, there was no DiI-labeled membrane around the nucleus in mature spores, whereas a DiI-labeled limit membrane wrapping nucleus was found at the tip of the extruded polar tube, suggesting that the membrane of sporoplasm was formed outside the mature spore. Two Nosema bombycis sporoplasm surface proteins (NbTMP1 and NoboABCG1.1) were located at the polaroplast in mature spores, in the extruded polar tube and on the sporoplasm membrane, which indicated that the polaroplast transported via the polar tube finally became the limiting membrane of the sporoplasm. Golgi-tracker green and Golgi marker protein syntaxin 6 were also found the same model, which was consistent with the transported polaroplast derived from Golgi transformed into the novel sporoplasm membrane during spore germination. ImportanceMicrosporidia, obligate intracellular pathogenic organisms, cause huge economic losses in agriculture and even threaten human health. The key to successful infection of microsporidia is its unique invasion apparatus which includes the polar filament, polaroplast and posterior vacuole. When the spore is activated to geminate, the polar filament uncoils and undergoes a rapid transition into the hollow polar tube that will transport the sporoplasm components including nucleus into a host cell to achieve the invasion. Knowledge of structure difference between polar filament and polar tube, the process of cargo transport in extruded polar tube, and the formation of the sporoplasm membrane are still poorly understood. Herein, we verify that the polar filament evaginates to form the polar tube, which serves as a conduit for transporting elongated nucleus and other sporoplasm components. And we confirm that the transported polaroplast finally transforms into the novel sporoplasm membrane during spore germination. Our study provides new insights into the cargo transportation process of polar tube and origin of the sporoplasm membrane, which serve as foundations for clarifying the microsporidian infection mechanism.

pathology↗

bioRxiv2022

A Genome Scale Transcriptional Regulatory Model of the Human Placenta

Gene regulation is essential to placental function and fetal development. We report a genome-scale transcriptional regulatory network (TRN) of the human placenta built using digital genomic footprinting and transcriptomic data. We integrated 475 transcriptomes and 12 DNase hypersensitivity datasets from placental samples to globally and quantitatively map transcription factor (TF)-target gene interactions. In an independent dataset, the TRN model predicted target gene expression with an out of sample R2 value greater than 0.25 for 74% of target genes. We performed siRNA knockdowns of 4 TFs and achieved concordance between the predicted gene targets in our TRN and differences in expression of knockdowns with an accuracy of >0.7 for 3 of the 4 TFs. Our final model contained 113,158 interactions across 391 TFs and 7,712 target genes and is publicly available. We identified six TFs which were significantly enriched as regulators for genes previously associated with preterm birth.

systems biology↗

bioRxiv2022

LRTK: A unified and versatile toolkit for analyzing linked-read sequencing data

Linked-read sequencing technologies generate high base quality reads that contain extrapolative information on long-range DNA connectedness. These advantages of linked-read technologies are well known and has been demonstrated in many human genomic and metagenomic studies. However, existing linked-read analysis pipelines (e.g., Long Ranger) were primarily developed to process sequencing data from the human genome and are not suited for analyzing metagenomic sequencing data. Moreover, linked-read analysis pipelines are typically limited to one specific sequencing platform. To address these limitations, we present the Linked-Read ToolKit (LRTK), a unified and versatile toolkit for platform agnostic processing of linked-read sequencing data from both human genomes and metagenomes. LRTK provides functions to perform linked-read simulation, barcode error correction, read cloud assembly, barcode-aware read alignment, reconstruction of long DNA fragments, taxonomic classification and quantification, as well as barcode-assisted genomic variant calling and phasing. LRTK has the ability to process multiple samples automatically, and provides the user with the option to generate reproducible reports during processing of raw sequencing data and at multiple checkpoints throughout downstream analysis. We applied LRTK on two benchmarking and three real linked-read data sets from both the human genome and metagenome. We showcase LRTKs ability to generate comparative performance results from the preceding benchmark study and to report these results in publication-ready HTML document plots. LRTK provides comprehensive and flexible modules along with an easy-to-use Python-based workflow for processing linked-read sequencing datasets, thereby filling the current gap in the field caused by platform-centric genome-specific linked-read data analysis tools.

bioinformatics↗

bioRxiv2022

Discovery of unknown quorum-sensing reprogramming factors in Pseudomonas aeruginosa using a dual-acting-gene-blocking approach

LasR is a master regulator of quorum-sensing (QS) in Pseudomonas aeruginosa. LasR-null mutants commonly appear in lung isolates from chronically infected cystic fibrosis (CF) patients. However, numerous such CF isolates have a QS-active phenotype, but factors underlying QS-reprogramming in LasR-null mutants remain largely unknown. Mutations in the transcriptional regulator gene mexT are well known to be responsible for QS-reprogramming in a laboratory LasR-null mutant strain, however, simultaneous occurrence of lasR and mexT mutations is rare in CF isolates. To identify QS-reprogramming determinants, we developed an experimental evolution approach, for which a QS-inactive LasR null mutant with an extra copy of mexT was engineered. In such a strain, spontaneous single mexT mutations are expected to have no or little phenotypic consequences. This novel method, named "targeted gene duplication followed by mutant screening" (TGD-MS), resulted in the identification of QS-active revertants with mutations in genes other than mexT. We characterized a QS-active revertant with a point mutation in rpoA, a gene encoding the -subunit of RNA polymerase. QS activation in this mutant was found to be associated with the down-regulated expression of mexEF-oprN efflux pump genes. Our study therefore uncovers a new functional role for RpoA in regulating QS activity. Furthermore, our results suggest that a regulatory circuit controlling the expression of the mexEF-oprN operon is critical for QS-reprogramming. In conclusion, our study reports on the identification of non-MexT proteins associated with QS-reprogramming in a laboratory strain, shedding light on possible QS activation mechanisms in clinical P. aeruginosa isolates.

microbiology↗

bioRxiv2022

Accurate strain-level microbiome composition analysis from short reads

Because bacterial strains can exhibit different biological properties, strain-level composition analysis plays a vital role in understanding the functions and dynamics of microbial communities. Metagenomic sequencing has become the major means for probing the microbial composition in host-associated or environmental samples. Despite a plethora of composition analysis tools, they are not optimized to address the challenges in strain-level analysis: a reference database with highly similar reference strain genomes and the presence of multiple strains under one species in a sample. In this work, we present a new strain-level composition analysis tool named StrainScan that employs a novel tree-based k-mer indexing structure to strike a balance between the strain identification accuracy and the computational complexity. We rigorously tested StrainScan on many simulated and real sequencing data and benchmarked StrainScan with popular strain-level analysis tools including Krakenuniq, StrainSeeker, Pathoscope2, Sigma, StrainGE, and Strainest. The results show that StrainScan has higher accuracy and resolution than the the state-of-the-art tools on strain-level composition analysis. It improves the F1-score by 20% in identifying multiple strains with at least 99.89% average nucleotide identity. StrainScan takes short reads and a set of reference strains as input and its source codes are freely available at https://github.com/liaoherui/strainScan.

bioinformatics↗

bioRxiv2021

hNOP2/NSUN1 Regulates Ribosome Biogenesis through Stabilization of snoRNP Complexes and Cytosine-5 Methylation of 28S rRNA.

5-Methylcytosine (m5C) is a base modification broadly found on various RNAs in the human transcriptome. In eukaryotes, m5C is catalyzed by enzymes of the NSUN family composed of seven human members (NSUN1-7). NOP2/NSUN1 has been primarily characterized in budding yeast as an essential ribosome biogenesis factor required for the deposition of m5C on the 25S ribosomal RNA (rRNA). Although human NOP2/NSUN1 has been known to be an oncogene overexpressed in several types of cancer, its functions and substrates remain poorly characterized. Here we used a miCLIP-seq approach to identify human NOP2/NSUN1 RNA substrates. Our analysis revealed that NOP2/NSUN1 catalyzes the deposition of m5C at position 4447 on the 28S rRNA. We also find that NOP2/NSUN1 binds to the 5ETS region of the pre-rRNA transcript and regulates pre-rRNA processing through non-catalytic complex formation with box C/D snoRNAs. We provide evidence that NOP2/NSUN1 facilitates the recruitment of U3 and U8 snoRNAs to pre-90S ribosomal particles and their stable assembly into snoRNP complexes. Remarkably, expression of both WT and catalytically inactive NOP2/NSUN1 in knockdown background rescues the rRNA processing defects and the stable assembly of box C/D snoRNP complexes, suggesting that NOP2/NSUN1-mediated deposition of m5C on rRNA is not required for ribosome synthesis.

molecular biology↗

bioRxiv2021

Augmenting Neutralization breadth against Diverse HIV-1 by increasing the Ab-Ag interface on V2

Understanding maturation pathways of broadly neutralizing antibodies (bnAbs) against HIV-1 in non-human primates can be highly informative for HIV-1 vaccine development. We now obtained a lineage of J038 from Chinese rhesus macaques after 7-years of SHIV infection. J038 has short complementary determining loops and neutralizes 54% of global circulating HIV-1 strains. Its binding induces a unique "up" conformation for one of the V2 loops in the trimeric envelope glycoprotein (Env) and is heavily dependent on glycan, which provides nearly half of the binding surface. The unmutated common ancestor of the J038 lineage antibodies binds monomeric gp120 and neutralizes the autologous virus. Continuous maturation enhances neutralization potency and breadth of J038 lineage antibodies via expanding antibody-Env contact areas surrounding the core region contacted by germline-encoded residues. Developmental details and recognition features of J038 lineage antibodies revealed here provide a new pathway for maturation elicitation of V2-targeting bnAbs. Highlights* Long-term infected NHPs develop antibodies neutralizing up to 54% of HIV-1 strains * Antibody J038 binds one V2 loop on HIV-1 Env trimer in a unique "up" position * UCA of the J038 lineage effectively neutralizes the autologous virus * J038 lineage antibodies mature through gradually increased contact to glycans

immunology↗

bioRxiv2021

TMT-based proteomic analysis of the antibiotic effects of ShangKeHuangShui against Straphylococcus aureus.

Post-traumatic infection is a serious orthopedic trauma complication commonly caused by Staphylococcus aureus (SAU). ShangKeHuangShui, also known as Yellow Aqueous Concentrate of Traumatology Herbs (YACTH), is prepared from six Chinese herbal medicines, which has been used for decades in our hospital to prevent post-traumatic infection. In the present study, we investigated the in vitro antibacterial effects and underlying mechanism of YACTH against SAU. YACTH exhibited significant antibacterial activity against SAU with the minimum inhibitory concentration (MIC) of 8.625 mg/mL. Proteomic analysis based on Tandem mass tag (TMT) showed different protein expression levels in SAU under the YACTH and control conditions. Compared to the control group, the expression level of 490 proteins of YACTH treated group significantly changed (>1.2 fold, P <0.05). Biological informatics analysis showed that these differential proteins were widely involved in a variety of biological processes and multiple metabolic pathways. We then selected 26 target proteins to further conduct Parallel reaction monitoring (PRM). The results revealed that the 9 down-regulated proteins were mainly involved in RNA polymerase, oxidative phosphorylation, ABC transporter and glycolysis; whereas, the 17 up-regulated proteins are related to RNA degradation, mismatch repair and ribosome. In conclusion, YACTH, which contains the water-soluble components of six Chinese herbs, is first reported to exhibit antibacterial activity against SAU in vitro. The results provide novel insights into the antibacterial mechanisms of YACTH on protein networks, which may help us find new potential antibiotic targets.

microbiology↗

bioRxiv2021

A recombinant protein containing influenza viral conserved epitopes and superantigen induces broad-spectrum protection

Influenza pandemic poses public health threats annually for lacking vaccine which provides cross-protection against novel and emerging influenza viruses. Combining conserved antigens inducing cross-protective antibody response with epitopes activating cross-protective cytotoxic T-cells would offer an attractive strategy for developing universal vaccine. In this study, we constructed a recombinant protein NMHC consisting of influenza viral conserved epitopes and superantigen fragment. NMHC promoted the mature of bone marrow-derived dendritic cells and induced CD4+ T cells to differentiate into Th1, Th2 and Th17 subtypes. Mice vaccinated with NMHC produced high level of immunoglobulins which cross-bound to HA fragments from six influenza virus subtypes with high antibody titers. Anti-NMHC serum showed potent hemagglutinin inhibition effects to highly divergent group 1 (H1 subtypes) and group 2 (H3 subtype) influenza virus strains. And purified anti-NMHC antibodies could bind to multiple HAs with high affinities. NMHC vaccination effectively protected the mice from infection and lung damage challenged by two subtypes of H1N1 influenza virus. Moreover, NMHC vaccination elicited CD4+ and CD8+ T-cell responses to clear the virus from infected tissue and prevent virus spreading. In conclusion, this study provided proof of concept for triggering both B cells and T cells immune responses against multiple influenza virus infection, and NMHC may be a potential candidate of universal broad-spectrum vaccine for various influenza virus prevention and therapy.

epidemiology↗

bioRxiv2021

Spike mutations in SARS-CoV-2 variants confer resistance to antibody neutralization

New SARS-CoV-2 variants continue to emerge from the current global pandemic, some of which can replicate faster and with greater transmissibility and pathogenicity. In particular, UK501Y.V1 identified in UK, SA501Y.V2 in South Africa, and BR501Y.V3 in Brazil are raising serious concerns as they spread quickly and contain spike protein mutations that may facilitate escape from current antibody therapies and vaccine protection. Here, we constructed a panel of 28 SARS-CoV-2 pseudoviruses bearing single or combined mutations found in the spike protein of these three variants, as well as additional nine mutations that within or close by the major antigenic sites in the spike protein identified in the GISAID database. These pseudoviruses were tested against a panel of monoclonal antibodies (mAbs), including some approved for emergency use to treat SARS-CoV-2 infection, and convalescent patient plasma collected early in the pandemic. SA501Y.V2 pseudovirus was the most resistant, in magnitude and breadth, against mAbs and convalescent plasma, followed by BR501Y.V3, and then UK501Y.V1. This resistance hierarchy corresponds with Y144del and 242-244del mutations in the N-terminal domain as well as K417N/T, E484K and N501Y mutations in the receptor binding domain (RBD). Crystal structural analysis of RBD carrying triple K417N-E484K-N501Y mutations found in SA501Y.V2 bound with mAb P2C-1F11 revealed a molecular basis for antibody neutralization and escape. SA501Y.V2 and BR501Y.V3 also acquired substantial ability to use mouse and mink ACE2 for entry. Taken together, our results clearly demonstrate major antigenic shifts and potentially broadening the host range of SA501Y.V2 and BR501Y.V3, which pose serious challenges to our current antibody therapies and vaccine protection.

immunology↗

bioRxiv2020

VirStrain: a strain identification tool for RNA viruses

1Genome epidemiology, which uses genomic data to analyze the source and spread of infectious diseases, provides important information beyond interview-based methods. Given fast accumulation of sequenced viral genomes, a basic need in genome epidemiology is to identify which reference genomes are identical or closest to the ones in a sequenced sample. Then the associated metadata such as the geographical locations can be utilized to infer the transmission network. In this work, we deliver VirStrain, a fast and accurate tool for conducting strain-level analysis from short reads. By using a greedy covering algorithm, we are able to derive unique k-mer combinations for highly similar reference genomes. VirStrain is able to detect the most possible strain and also multiple strains that may simultaneously infect the same host. We tested VirStrain on three types of RNA viruses whose reference genomes have different similarity distri-butions. For each types of virus, we assessed VirStrain across multiple bench-mark datasets of different properties and complexity. The experimental results on both simulated and real sequencing data show that VirStrain outperforms other strain identification tools.

bioinformatics↗