Biology subjects

Yang, X.

Publications and source records attributed to Yang, X..

At least 847 records · Page 47Linked to original sources

bioRxiv2020

A Novel Non-hypermucoviscous ST11 Hypervirulent Carbapenem-resistant Klebsiella pneumoniae Lacking Classical Virulence Factors

BackgroundHypervirulent Klebsiella pneumoniae lacking classical virulence factors is uncommon, and the virulence mechanisms of this organism are not understood. MethodsFollowing a retrospective study of carbapenem-resistant K. pneumoniae based on core genome multilocus sequence typing (cgMLST), isolates that caused high mortality were investigated with a genome-wide association study (GWAS), proteome analysis and an animal model. ResultsThe sublineage of sequence type 11 (ST11) K. pneumoniae, which belongs to complex type 3176 (CT3176) and K-locus 47 (KL47), was highlighted due to the high mortality of infected patients. GWAS analysis showed that ampR was associated with the CT3176 isolates. In a mouse model, the mortality of ampR-carrying isolates was comparable to that of the typical hypervirulent isolate GM2. Even during the first 24 hours of infection, the bacterial load and pathological changes of the ampR-carrying isolates in the lungs were more severe than those of GM2. The ampR complement mutant was able to enhance the virulence of the KL47 isolate but not the virulence of KL1. Proteome analysis showed that the expression of WcaJ in the ampR+ isolates was significantly higher than that in the ampR- isolates, and this result was also confirmed by transcription tests and capsule staining. It is suggested that the enhancement of the initial stage of capsule synthesis may be the cause of the high virulence of these non-hypermucoviscous ST11 carbapenem-resistant K. pneumoniae isolates. ConclusionsNon-hypermucoviscous ST11 hypervirulent carbapenem-resistant K. pneumoniae warrants continued surveillance and investigation.

microbiology↗

bioRxiv2020

Shape-to-graph Mapping Method for Efficient Characterization and Classification of Complex Geometries in Biological Images

With the ever-increasing quality and quantity of imaging data in biomedical research comes the demand for computational methodologies that enable efficient and reliable automated extraction of the quantitative information contained within these images. One of the challenges in providing such methodology is the need for tailoring algorithms to the specifics of the data, limiting their areas of application. Here we present a broadly applicable approach to quantification and classification of complex shapes and patterns in biological or other multi-component formations. This approach integrates the mapping of all shape boundaries within an image onto a global information-rich graph and machine learning on the multidimensional measures of the graph. We demonstrated the power of this method by (1) extracting subtle structural differences from visually indistinguishable images in our phenotype rescue experiments using the endothelial tube formations assay, (2) training the algorithm to identify biophysical parameters underlying the formation of different multicellular networks in our simulation model of collective cell behavior, and (3) analyzing the response of U2OS cell cultures to a broad array of small molecule perturbations. Author SummaryIn this paper, we present a methodology that is based on mapping an arbitrary set of outlines onto a complete, strictly defined structure, in which every point representing the shape becomes a terminal point of a global graph. Because this mapping preserves the whole complexity of the shape, it allows for extracting the full scope of geometric features of any scale. Importantly, an extensive set of graph-based metrics in each image makes integration with machine learning routines highly efficient even for a small data sets and provide an opportunity to backtrack the subtle morphological features responsible for the automated distinction into image classes. The resulting tool provides efficient, versatile, and robust quantification of complex shapes and patterns in experimental images.

bioinformatics↗

bioRxiv2020

Genes and Pathways for Plasma Lipid Traits via Multi-tissue Multi-omics Systems Analysis

Genome-wide association studies (GWAS) have implicated [~]380 genetic loci for plasma lipid regulation. However, these loci only explain 17-27% of the trait variance and a comprehensive understanding of the molecular mechanisms has not been achieved. In this study, we utilized an integrative genomics approach leveraging diverse genomic data from human populations to investigate whether genetic variants associated with various plasma lipid traits, namely total cholesterol (TC), high and low density lipoprotein cholesterol (HDL and LDL), and triglycerides (TG), from GWAS were concentrated on specific parts of tissue-specific gene regulatory networks. In addition to the expected lipid metabolism pathways, gene subnetworks involved in interferon signaling, autoimmune/immune activation, visual transduction, and protein catabolism were significantly associated with all lipid traits. Additionally, we detected trait-specific subnetworks, including cadherin-associated subnetworks for LDL, glutathione metabolism for HDL, valine, leucine and isoleucine biosynthesis for TC, and insulin signaling and complement pathways for TG. Finally, utilizing gene-gene relations revealed by tissue-specific gene regulatory networks, we detected both known (e.g. APOH, APOA4, and ABCA1) and novel (e.g. F2 in adipose tissue) key regulator genes in these lipid-associated subnetworks. Knockdown of the F2 gene (Coagulation Factor II, Thrombin) in 3T3-L1 and C3H10T1/2 adipocytes reduced gene expression of Abcb11, Apoa5, Apof, Fabp1, Lipc, and Cd36, reduced intracellular adipocyte lipid content, and increased extracellular lipid content, supporting a link between adipose thrombin and lipid regulation. Our results shed light on the complex mechanisms underlying lipid metabolism and highlight potential novel targets for lipid regulation and lipid-associated diseases.

systems biology↗

bioRxiv2020

Structure-based drug design, virtual screening and high-throughput screening rapidly identify antiviral leads targeting COVID-19

A new coronavirus (CoV) identified as COVID-19 virus is the etiological agent responsible for the 2019-2020 viral pneumonia outbreak that commenced in Wuhan1-4. Currently there is no targeted therapeutics and effective treatment options remain very limited. In order to rapidly discover lead compounds for clinical use, we initiated a program of combined structure-assisted drug design, virtual drug screening and high-throughput screening to identify new drug leads that target the COVID-19 virus main protease (Mpro). Mpro is a key CoV enzyme, which plays a pivotal role in mediating viral replication and transcription, making it an attractive drug target for this virus5,6. Here, we identified a mechanism-based inhibitor, N3, by computer-aided drug design and subsequently determined the crystal structure of COVID-19 virus Mpro in complex with this compound. Next, through a combination of structure-based virtual and high-throughput screening, we assayed over 10,000 compounds including approved drugs, drug candidates in clinical trials, and other pharmacologically active compounds as inhibitors of Mpro. Six of these inhibit Mpro with IC50 values ranging from 0.67 to 21.4 M. Ebselen also exhibited promising antiviral activity in cell-based assays. Our results demonstrate the efficacy of this screening strategy, which can lead to the rapid discovery of drug leads with clinical potential in response to new infectious diseases where no specific drugs or vaccines are available.

biochemistry↗

bioRxiv2020

A non-canonical histone acetyltransferase targets intragenic enhancers and regulates plant architecture

Axillary meristem development determines both plant architecture and crop yield; this critical process is regulated by the TCP transcription factor (TF) family, including the maize TB1 and Arabidopsis BRC1. Studies have shown that both TB1 and AtBRC1 can target the gene body regions of some target genes and activate their expression; however, the regulatory mechanisms remain largely unknown. Here, we show that a cucumber CYC/TB1 homologue, TEN, controls the identity and mobility of tendrils. Through its C-terminus, TEN binds at intragenic enhancers of target genes; its N-terminal domain functions as a novel, non-canonical histone acetyltransferase (HAT) to preferentially act on lysine 56 and 122, of the histone H3 globular domain. This HAT activity is responsible for chromatin loosening and host gene activation. The N-termini of all tested CYC/TB1-like proteins contain an intrinsically disordered region (IDR), and despite their sequence divergence, they have conserved HAT activity. This study discovered a non-canonical class of HATs, and as well, provides a mechanism by which modification at the H3 globular domain is integrated with the transcription process.

plant biology↗

bioRxiv2020

3D Epigenomic Characterization Reveals Insights Into Gene Regulation and Lineage Specification During Corticogenesis

Lineage-specific epigenomic changes during human corticogenesis have previously remained elusive due to challenges with tissue heterogeneity and sample availability. Here, we analyze cis-regulatory chromatin interactions, open chromatin regions, and transcriptomes for radial glia, intermediate progenitor cells, excitatory neurons, and interneurons isolated from mid-gestational human brain samples. We show that chromatin looping underlies transcriptional regulation for lineage-specific genes, with transcription factor motifs, families of transposable elements, and disease-associated variants enriched at distal interacting regions in a cell type-specific manner. A subset of promoters exhibit unusually high degrees of chromatin interactivity, which we term super interactive promoters. Super interactive promoters are enriched for critical lineage-specific genes, suggesting that interactions at these loci contribute to the fine-tuning of cell type-specific transcription. Finally, we present CRISPRview, a novel approach for validating distal interacting regions in primary cells. Our study presents the first characterization of cell type-specific 3D epigenomic landscapes during human corticogenesis, advancing our understanding of gene regulation and lineage specification during human brain development.

genomics↗

bioRxiv2020

Modulation of metabolic functions through Cas13d-mediated gene knockdown in liver

RNA knockdown in vivo carries significant potential for disease modelings and therapies. Despite the emerging approaches of CRISPR/Cas9-mediated permanent knock out of targeted genes, strategies targeting RNA for disruption are advantageous in the treatment of acquired metabolic disorders when permanent modification of the genome DNA is not appropriate, and RNA virus infection diseases when pathogenic DNA is not available (such as SARS-Cov-2 and MERS infections). Recently, Cas13d, a family of RNA-targeting CRISPR effectors, has been shown to accomplish robust down-regulation of cellular RNAs in mammalian cells in vitro. Among the various Cas13d subtypes, CasRx (RfxCas13d) showed the most potent RNA knockdown efficiency in HEK293T cells. However, the RNA-targeting activity of Cas13d still needs to be verified in vivo. In this study, the CasRx system was demonstrated to efficiently and functionally knock down genes related to metabolism functions, including Pten, Pcsk9 and lncLstr, in mouse hepatocytes. CasRx-mediated simultaneous knockdown of multiple genes was also achieved by sgRNA arrays, providing a useful strategy to modulate complex metabolism networks. Moreover, the AAV (adeno-associated virus)-mediated delivery of CasRx and Pcsk9 sgRNAs into mouse liver successfully decreased serum PCSK9, resulting in significant reduction of serum cholesterol levels. Importantly, CasRx-mediated knockdown of Pcsk9 is reversible and Pcsk9 could be repeatedly down-regulated, providing an effective strategy to reversibly modulate metabolic genes. The present work supplies a successful proof-of-concept trial that suggests efficient and regulatory knockdown of target metabolic genes for a designed metabolism modulation in the liver.

genomics↗

bioRxiv2020

Proteomic and phosphoproteomic analysis identifies novel liver-related signaling in retinal pigment epithelial cells during epithelial-mesenchymal transition

Epithelial-mesenchymal transition (EMT) of the retinal pigment epithelium (RPE) is associated with several potentially blinding retinal diseases. Proteomic and phosphoproteomic studies were performed on human pluripotent stem cell-derived RPE (hPSC-RPE) monolayers to better understand the pathways mediating RPE EMT. EMT was induced by enzymatic dissociation or by co-treatment with transforming growth factor beta (TGF{beta}) and tumor necrosis factor alpha (TNF; TGNF). The global and phosphoproteomes were analyzed at 1 hr post EMT induction to capture early events in kinase/phosphatase signaling cascades and at 12 hrs to define early changes in protein abundance. Pathway enrichment analysis revealed that TGNF and Dissociation rapidly perturbed signaling in many of the same pathways, with striking similarity in the phosphoproteome at 1 hr. Surprisingly, functions related to liver cell proliferation and hyperplasia were strongly enriched in the phosphosites altered by both treatments at 1 hr and in protein abundance changes at 12 hrs. Hepatocyte Growth Factor-cMET signaling exhibited the strongest overall enrichment in both treatments. These signaling pathways may serve as suitable targets for the development of therapeutic strategies for the inhibition of RPE EMT, and thus progression of several debilitating visual diseases.

cell biology↗

bioRxiv2020

Exploring spatiotemporal changes in ecosystem service values and hotspots in Southwest of China, Mekong Region

Xishuangbanna in the southwestern border of China is located in the upper reaches of the Mekong River between the Indo-China Peninsula and the East Asian continent. It is the largest tropical rain forest and monsoon forest in China. They have an irreplaceable ecological service function and are an important barrier to maintaining the ecological security of the Mekong River transboundary basin of the Lancang River. Based on three sets of remote sensing data (1996, 2003, 2010 and 2016), this study has made an exploration on spatio-temporal changes of Xishuangbanna, and also made an assessment on different ecosystem values of six types of ecosystem in Xishuangbanna based on related theories of ecological economics. Results showed that the values of Xishuangbanna ecosystem services in 1996, 2003, 2010, and 2016 were 70.4014billion yuan, 70.2115 billion yuan, 68.5129 billion yuan and 63.6098 billion yuan, respectively. The total value shows a continuous decreasing trend, reflecting the continuous decline in the ability of the Xishuangbanna ecosystem to provide services to humans. If divided by ecosystem types, forest and rubber were two types that have the greatest proportion of service values. In the perspective of service types, soil formation and protection account for the largest proportion, followed by gas regulation and biodiversity protection. Studying Xishuangbannas ecosystem service values is helpful to explore the sustainable development of resources and economy. HighlightThis paper used coefficient of sensitivity to determine the dependence of ESV on the change of ecosystem value coefficient over time. The total amount of ESV shows a continuous downward trend, indicating that the ecological environment of Xishuangbanna is still severe. The temporal-spatial change of ESV was analyzed for two decades.

ecology↗

bioRxiv2020

Prophylactic and therapeutic HBV vaccination by an HBs-expressing cytomegalovirus vector lacking an interferon antagonist

Cytomegalovirus (CMV)-based vaccines show promising effects against chronic infections in non-human primates. Therefore, we examined the potential of HBV vaccines based on mouse CMV (MCMV) vectors expressing the small HBsAg. Immunological consequences of vaccine virus attenuation were addressed by either replacing the dispensable gene m157 ( MCMV-HBs) or the gene M27 ( {Delta}M27-HBs), the latter encodes a potent interferon antagonist targeting the transcription factor STAT2. M27 was chosen, since human cytomegalovirus (HCMV) encodes an analogous gene product, which also induced proteasomal STAT2 degradation by exploiting Cullin RING ubiquitin ligases. Vaccinated mice were challenged with HBV through hydrodynamic injection. MCMV-HBs and {Delta}M27-HBs vaccination achieved accelerated HBV clearance in serum and liver as well as robust HBV-specific CD8+ T cell responses. When we explored the therapeutic potential of MCMV-based vaccines, especially the combination of {Delta}M27-HBs prime and DNA boost vaccination resulted in increased intrahepatic HBs-specific CD8+ T cell responses and HBV clearance in persistently infected mice. Our results demonstrated that vaccines based on a replication competent MCMV attenuated through the deletion of an interferon antagonist targeting STAT2 elicit robust anti-HBV immune responses and mediate HBV clearance in mice in prophylactic and therapeutic immunization regimes.

immunology↗

bioRxiv2020

Shifts in gut microbiome and metabolome are associated with risk of recurrent atrial fibrillation

Specific alterations of gut microbiota (GM) in atrial fibrillation (AF) patients, including elevated microbial diversity, particularly perturbed composition, imbalanced microbial function, and associated metabolic pattern modifications have been described in our previous report. The current work aimed to assess the association of GM composition with AF recurrence (RAF) after ablation, and to construct a GM-based predictive model for RAF. Gut microbial composition and metabolic profiles were assessed based on metagenomic sequencing and metabolomic analyses. Compared with non-AF controls (50 individuals), GM composition and metabolomic profile were significantly altered between patients with recurrent AF (17 individuals) and the non-RAF group (23 individuals). Notably, discriminative taxa between the non-RAF and RAF groups, including the families Nitrosomonadaceae and Lentisphaeraceae, the genera Marinitoga and Rufibacter, and the species Faecalibacterium sp. CAG:82, Bacillus gobiensis, and Desulfobacterales bacterium PC51MH44, were selected to construct a taxonomic scoring system based on LASSO analysis. An elevated area under curve (0.954) and positive net reclassification index (1.5601) for predicting RAF compared with traditional clinical scoring (AUC=0.6918) were obtained. The GM-based taxonomic scoring system theoretically improves the model performance. These data provide novel evidence that supports incorporating the GM factor into future recurrent risk stratification.

genomics↗

bioRxiv2020

Chlorotoxin Redirects Chimeric Antigen Receptor T Cells for Specific and Effective Targeting of Glioblastoma

While chimeric antigen receptor (CAR) T cells have demonstrated antitumor activity against glioblastoma (GBM), tumor heterogeneity remains a critical challenge. To more effectively target heterogeneous GBMs, we report the development of a novel peptide-based CAR exploiting the GBM-binding potential of chlorotoxin (CLTX). CLTX bound a greater proportion of tumor cells than GBM-associated antigens EGFR, HER2 and IL13R2. CAR T cells bearing CLTX as the targeting domain (CLTX-CAR), mediated potent in vitro and in vivo anti-GBM activity, and efficiently targeted tumors lacking expression of other GBM-associated antigens. Importantly, CLTX-CAR T cells exhibited no observable off-target effector activity against normal cells, or when adoptively transferred into mice. Effective targeting by CLTX-CAR T cells required cell surface expression of matrix metalloproteinase-2 (MMP-2). Our results are the first demonstration of a peptide toxin utilized as a CAR targeting domain, expanding the repertoire of tumor-selective CAR T cells with the potential to reduce antigen escape. One Sentence SummaryChimeric antigen receptors incorporating chlorotoxin as the tumor targeting domain recognize and kill glioblastoma with high specificity and potency.

immunology↗

bioRxiv2020

Proteogenomic single cell analysis of skeletal muscle myocytes

Skeletal muscle myocytes have evolved into slow and fast-twitch types. These types are functionally distinct as a result of differential gene and protein expression. However, an understanding of the complexity of gene and protein variation between myofibers is unknown. We performed deep, whole cell, single cell RNA-seq on intact and fragments of skeletal myocytes from the mouse flexor digitorum brevis muscle. We compared the genomic expression data of 171 of these cells with two human proteomic datasets. The first was a spatial proteomics survey of mosaic patterns of protein expression utilizing the Human Protein Atlas (HPA) and the HPASubC tool. The second was a mass-spectrometry (MS) derived proteomic dataset of single human muscle fibers. Immunohistochemistry and RNA-ISH were used to understand variable expression. scRNA-seq identified three distinct clusters of myocytes (a slow/fast 2A cluster and two fast 2X clusters). Utilizing 1,605 mosaic patterned proteins from visual proteomics, and 596 differentially expressed proteins by MS methods, we explore this fast 2X division. Only 36 genes/proteins had variable expression across all three studies, of which nine are newly described as variable between fast/slow twitch myofibers. An additional 414 genes/proteins were identified as variable by two methods. Immunohistochemistry and RNA-ISH generally validated variable expression across methods presumably due to species-related differences. In this first integrated proteogenomic analysis of mature skeletal muscle myocytes we confirm the main fiber types and greatly expand the known repertoire of twitch-type specific genes/proteins. We also demonstrate the importance of integrating genomic and proteomic datasets.

genomics↗

bioRxiv2020

SMART-Q: An Integrative Pipeline Quantifying Cell Type-Specific RNA Transcription

Accurate RNA quantification at the single-cell level is critical for understanding the dynamics of gene expression and regulation across space and time. Single molecule FISH (smFISH), such as RNAscope, provides spatial and quantitative measurements of individual transcripts, therefore, can be used to explore differential gene expression among a heterogeneous cell population if combined with cell identify information. However, such analysis is not straightforward, and existing image analysis pipelines cannot integrate both RNA transcripts and cellular staining information to automatically output cell type-specific gene expression. We developed an efficient and customizable analysis method, Single-Molecule Automatic RNA Transcription Quantification (SMART-Q), to enable the analysis of gene transcripts in a cell type-specific manner. SMART-Q efficiently infers cell identity information from multiplexed immuno-staining and quantifies cell type-specific transcripts using a 3D Gaussian fitting algorithm. Furthermore, we have optimized SMART-Q for user experiences, such as flexible parameters specification, batch data outputs, and visualization of analysis results. SMART-Q meets the demands for efficient quantification of single-molecule RNA and can be widely used for cell type-specific RNA transcript analysis.

cell biology↗

bioRxiv2020

Regulation of olfactory-based sex behaviors in the silkworm by genes in the sex-determination cascade

Insect courtship and mating depend on integration of olfactory, visual, and tactile cues. Compared to other insects, Bombyx mori, the domesticated silkworm, has relatively simple sexual behaviors as it cannot fly. Here by using CRISPR/Cas and electrophysiological techniques we found that courtship and mating behaviors are regulated in male silk moths by mutating genes in the sex determination cascade belonging to two conserved pathways. Loss of Bmdsx gene expression significantly reduced the peripheral perception of the major pheromone component bombykol by reducing expression of the product of the BmOR1 gene which completely blocked courtship in adult males. Interestingly, we found that mating behavior was regulated independently by another sexual differentiation gene, Bmfru. Loss of Bmfru completely blocked mating, but males displayed normal courtship behavior. Lack of Bmfru expression significantly reduced the perception of the minor pheromone component bombykal due to the down regulation of BmOR3 expression; further, functional analysis revealed that loss of the product of BmOR3 played a key role in terminating male mating behavior. Our results suggest that Bmdsx and Bmfru are at the base of the two primary pathways that regulate olfactory-based sexual behavior. Author SummaryThe fundamental insect sexual behaviors, courtship and mating, result from successful integration of olfactory, vision, tactile and other complex innate behaviors. In the widely used insect model, Drosophila melanogaster, the sex determination cascade genes fruitless and doublesex are involved in the regulation of courtship and mating behaviors; however, little is known about the function of these sexual differentiation genes in regulating sex behaviors of Lepidoptera. Here we combine genetics and electrophysiology to investigate regulation pathway of sexual behaviors in the model lepidopteran insect, the domesticated silk moth, Bombyx mori. Our results support the presence of two genetic pathways in B. mori, named Bmdsx-BmOR1-bombykol and Bmfru-BmOR3-bombykal, which control distinct aspects of male sexual behavior that are modulated by olfaction. This is the first comprehensive report about the role of sex differentiation genes in the male sexual behavior in the silk moth.

genetics↗

bioRxiv2020

Genomic and protein structure modelling analysis depicts the origin and infectivity of 2019-nCoV, a new coronavirus which caused a pneumonia outbreak in Wuhan, China

Detailed genomic and structure-based analysis of a new coronavirus, namely 2019-nCoV, showed that the new virus is a new type of bat coronavirus and is genetically fairly distant from the human SARS coronavirus. Structure analysis of the spike (S) protein of this new virus showed that its S protein only binds weakly to the ACE2 receptor on human cells whereas the human SARS coronavirus exhibits strongly affinity to the ACE receptor. These findings suggest that the new virus does not readily transmit between humans and should theoretically not able to cause very serious human infection. These data are important to guide design of infection control policy and inform the public on the nature of threat imposed by 2019-nCov when results of direct laboratory tests on this virus are not expected to be available in the near future.

microbiology↗

bioRxiv2020

Activation of Src-family kinases orchestrate secretion of flaviviruses by targeting mature progeny virions to secretory autophagosomes

Among the various host cellular processes that are hijacked by flaviviruses, very few mechanisms have been described with regard to viral secretion. Here we investigated how flaviviruses exploit the Src family kinases (SFKs) for exit from infected cells. We isolated three members of the SFK family - Src, Fyn and Lyn - that were specifically activated during secretion of Dengue and Zika or their corresponding virus like particles (VLPs). Pharmacological inhibition or genetic depletion of the SFKs blocked virus secretion, most significantly upon Lyn-deficiency. Lyn-/- cells were severely impaired in virus release, and were rescued when reconstituted with wild-type Lyn, but not a kinase- or palmitoylation-deficient Lyn mutant. We further established that Lyn, via its palmitoylation-dependent membrane association, triggered post-Golgi virus transport in specialised Rab11 and Transferrin receptor positive organelles resembling secretory autophagosomes, and distinct from conventional exocytic vesicles. In the absence of Lyn activity or its aberrant membrane association, virions were sorted into the lysosomal pathway for degradation. This mode of export was specifically triggered by processed, and mature, but not by furin-resistant virus particles, and occurred with significantly faster kinetics than the conventional secretory pathway. Our study therefore charts a previously undiscovered Lyn-dependent exit strategy, triggered by flaviviruses in secretory autophagosomes that might enable them to evade circulating antibodies and dictate tissue tropism.

microbiology↗

bioRxiv2020

MSIsensor-pro: fast, accurate and matched-normal-sample-free detection of microsatellite instability

We developed MSIsensor-pro (https://github.com/xjtu-omics/msisensor-pro), an open-source single sample microsatellite instability (MSI) scoring method for research and clinical applications. MSIsensor-pro introduces a multinomial distribution model to quantify polymerase slippages for each tumor sample and a discriminative sites selection method to enable MSI detection without matched normal samples. For samples of various sequencing depths and tumor purities, MSIsensor-pro significantly outperformed the current leading methods in terms of both accuracy and computational cost.

bioinformatics↗