Biology subjects

Wang, K.

Publications and source records attributed to Wang, K..

At least 469 records · Page 26Linked to original sources

bioRxiv2020

Multi-epitope vaccine design using an immunoinformatics approach for 2019 novel coronavirus in China (SARS-CoV-2)

A new coronavirus SARS-CoV-2 has caused over 9.2 million infection cases and 475758 deaths worldwide. Due to the rapid dissemination and the unavailability of specific therapy, there is a desperate need for vaccines to combat the epidemic of SARS-CoV-2. An in silico approach based on the available virus genome was applied to identify 19 high immunogenic B-cell epitopes and 499 human-leukocyte-antigen (HLA) restricted T-cell epitopes. Thirty multi-epitope peptide vaccines were designed by iNeo Suite, and manufactured by solid-phase synthesis. Docking analysis showed stable hydrogen bonds of epitopes with their corresponding HLA alleles. When four vaccine peptide candidates from the spike protein of SARS-CoV-2 were selected to immunize mice, a significantly larger amount of IgG in serum as well as an increase of CD19+ cells in ILNs was observed in peptide-immunized mice compared to the control mice. The ratio of IFN-{gamma}-secreting lymphocytes in CD4+ or CD8+ cells in the peptides-immunized mice were higher than that in the control mice. There were also a larger number of IFN-{gamma}-secreting T cells in spleen in the peptides-immunized mice. This study screened antigenic B-cell and T-cell epitopes in all encoded proteins of SARS-CoV-2, and further designed multi-epitope based peptide vaccine against viral structural proteins. The obtained vaccine peptides successfully elicited specific humoral and cellular immune responses in mice. Primate experiments and clinical trial are urgently required to validate the efficacy and safety of these vaccine peptides. ImportanceSo far, a new coronavirus SARS-CoV-2 has caused over 9.2 million infection cases and 475758 deaths worldwide. Due to the rapid dissemination and the unavailability of specific therapy, there is a desperate need for vaccines to combat the epidemic of SARS-CoV-2. Different from the development approaches for traditional vaccines, the development of our peptide vaccine is faster and simpler. In this study, we performed an in silico approach to identify the antigenic B-cell epitopes and human-leukocyte-antigen (HLA) restricted T-cell epitopes, and designed a panel of multi-epitope peptide vaccines. The resulting SARS-CoV-2 multi-epitope peptide vaccine could elicit specific humoral and cellular immune responses in mice efficiently, displaying its great potential in our fight of COVID-19.

bioinformatics↗

bioRxiv2020

Tracing the origin of a new organ by inferring the genetic basis of rumen evolution

The rumen is the hallmark organ of ruminants and hosts a diverse ecosystem of microorganisms that facilitates efficient digestion of plant fibers. We used 897 transcriptomes from three Cetartiodactyla lineages: ruminants, camels and cetaceans, as well as data from ruminant comparative genomics and functional assays to explore the genetic basis of rumen origin and evolution. Comparative analyses reveal that the rumen and the first-chamber stomachs of camels and cetaceans shared a common tissue origin from the esophagus. The rumen recruited genes from other tissues/organs and up-regulated many esophagus genes to aquire functional innovations involving epithelium absorption, improvement of the ketone body metabolism and regulation of microbial community. These innovations involve such genetic changes as ruminant-specific conserved elements, newly evolved genes and positively selected genes. Our in vitro experiements validate the functions of one enhancer, one positively selected gene and two newly evolved antibacterial genes. Our study provides novel insights into the origin and evolution of a complex organ.

evolutionary biology↗

bioRxiv2020

Constitutive activation of leucine-rich repeat receptor kinase signaling pathways by BAK1-interacting receptor-like kinase 3 chimera

Receptor kinases with extracellular leucine-rich repeat domains (LRR-RKs) form the largest group of membrane signaling proteins in plants. LRR-RKs can sense small molecule, peptide or protein ligands, and may be activated by ligand-induced interaction with a shape complementary SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASE (SERK) co-receptor kinase. We have previously shown that SERKs can also form constitutive, ligand-independent complexes with the LRR ectodomains of BAK1-interacting receptor-like kinase 3 (BIR3) receptor pseudokinases, negative regulators of LRR-RK signaling. Here we report that receptor chimaera in which the extracellular LRR domain of BIR3 is fused to the cytoplasmic kinase domains of the SERK-dependent LRR-RKs BRASSINOSTEROID INSENSITIVE1, HAESA and ERECTA form tight complexes with endogenous SERK co-receptors in the absence of ligand stimulus. Expression of these chimaera under the control of the endogenous promoter of the respective LRR-RK leads to strong gain-of-function brassinosteroid, floral abscission and stomatal patterning phenotypes, respectively. Importantly, a BIR3-GSO1/SGN3 chimera can partially complement sgn3 Casparian strip formation phenotypes, suggesting that GSO1/SGN3 receptor activation is also mediated by SERK proteins. Collectively, our protein engineering approach may be used to elucidate the physiological functions of orphan LRR-RKs and to identify their receptor activation mechanism in single transgenic lines.

plant biology↗

bioRxiv2020

Whole exome precision oncology targeting synthetic lethal vulnerabilities across the tumor transcriptome

Precision oncology has made significant advances in the last few years, mainly by targeting actionable mutations in cancer driver genes. However, the proportion of patients whose tumors can be targeted therapeutically remains limited. Recent studies have begun to explore the benefit of analyzing tumor transcriptomics data to guide patient treatment, raising the need for new approaches for systematically accomplishing that. Here we show that computationally derived genetic interactions can successfully predict patient response. Assembling a broad repertoire of 32 datasets spanning more than 1,500 patients and including both tumor transcriptomics and response data, we predicted the response in 17 out of 21 targeted and 8 out of 11 checkpoint therapy datasets across 8 different cancer types with considerable accuracy, without ever training on these datasets. Analyzing the recently published multi-arm WINTHER trial, we show that the fraction of patients benefitting from transcriptomic-based treatments could potentially be markedly increased from 15% to about 85% by targeting synthetic lethal vulnerabilities in their tumors. In summary, this is the first computational approach to obtain considerable predictive performance across many different targeted and immunotherapy datasets, providing a promising new way for guiding cancer treatment based on the tumor transcriptomics of cancer patients.

cancer biology↗

bioRxiv2020

Branched chain amino acid aminotransferase 2 Regulates Ferroptotic Cell Death in Cancer Cells

Ferroptosis has been implicated as a tumor-suppressor function for cancer therapy. Recently the sensitivity to ferroptosis was tightly linked to numerous biological processes, including metabolism of amino acid. Here, using a high-throughput CRISPR/Cas9 based genetic screen in HepG2 cells to search for metabolic proteins inhibiting ferroptosis, we identified branched chain amino acid aminotransferase 2 (BCAT2) as a novel suppressor of ferroptosis. Mechanistically, ferroptosis inducers (erastin, sorafenib and sulfasalazine) activated AMPK/SREBP1 signaling pathway through ferritinophagy, which in turn inhibited BCAT2 transcription. We further confirmed that BCAT2 mediating the metabolism of sulfur amino acid, regulated intracellular glutamate level, whose activation by ectopic expression specifically antagonize system Xc- inhibition and protected liver and pancreatic cancer cells from ferroptosis in vitro and in vivo. Finally, our results demonstrate the synergistic effect of sorafenib and sulfasalazine in downregulating BCAT2 expression and dictating ferroptotic death, where BCAT2 can also be used to predict the responsiveness of cancer cells to ferroptosis-inducing therapies. Collectively, these findings identify a novel role of BCAT2 in ferroptosis, suggesting a potential therapeutic strategy for overcoming sorafenib resistance.

cancer biology↗

bioRxiv2020

Characterization of a novel NDM-5-harboring plasmid from a carbapenem-resistant Escherichia coli isolate from China

A carbapenem-resistant Escherichia coli (sequence type 5415) strain was isolated from a male patient. S1-PFGE and Southern blotting showed that the blaNDM-5 gene was located on a novel 66-kb IncFII [F2:A-:B-] plasmid. Conjugation assays revealed that the blaNDM-5-bearing plasmid was self-transferrable. Genomic sequencing and comparative analysis suggested that plasmid p2947-NDM5 likely originated from a combination of an IncFII-type backbone and the blaNDM-5 flanking genetic elements. This study highlights the genetic complexity of an NDM-5 carbapenemase and the urgent need for continuous active monitoring. IMPORTANCECarbapenem resistance due to the NDM enzyme has become a serious clinical problem in medical care and public health. We here identified a blaNDM-5-positive E. coli strain ST5414. The blaNDM-5 gene was located on a novel self-transferrable IncFII type plasmid p2947-NDM5. Genomic sequencing and comparative analysis suggested that plasmid p2947-NDM5 likely originated from a combination of an IncFII-type backbone and the blaNDM-5 flanking genetic elements. The genetic context of NDM-5 is highly similar to that of animal origins, and we speculate that the blaNDM-harboring IncFII plasmid has a potential risk of being transmitted from animals to humans and should be paid more attention. Our findings highlight the threat of NDM-5 carbapenemase circulation and the urgency of stringent surveillance and control measures.

genomics↗

bioRxiv2020

Alteration of fecal microbial compositions and bacterial taxa in female osteoporotic patients

BackgroundGut microbiota, mainly characterized by fecal bacterial compositions, affects human immune system and pathophysiological development. Our aim was to measure the quantitative differences of fecal bacterial compositions between osteoporotic patients and healthy subjects, and to identify novel bacterial taxa that speculate the incidence of osteoporosis in female. MethodWe recruited 104 female subjects, including 45 osteoporotic individuals and 59 healthy control. Fecal samples were collected for further analysis by 16S rRNA quantitative arrays and bioinformatics analysis. ResultsAnalyses of - and {beta}-diversity demonstrated that the diversity and composition of fecal bacterial compositions were both significant different in osteoporosis group, as compared with healthy group. Multiple bacterial genera were significantly increased (e.g., Roseburia and Bacteroides) or decreased (e.g., Streptococcus and Dorea) in the osteoporotic cases. Furthermore, the osteoporosiscould be efficiently determined by the random forest model based on differential taxa (area under ROC curve = 0.93). ConclusionThere were obvious different fecal microbial characteristics between female osteoporosis and healthy subjects. These findings provided evidence for understanding the host-gut microbiota interplay in female osteoporosis, and supported clinical applications of gut microbiota analysis for female osteoporosis diagnosis

microbiology↗

bioRxiv2020

Surveying Brain Tumor Heterogeneity by Single-Cell RNA Sequencing of Multi-sector Biopsies

Brain tumors are among the most challenging human tumors for which the mechanisms driving progression and heterogeneity remain poorly understood. We combined single-cell RNA-seq with multisector biopsies to sample and analyze single-cell expression profiles of gliomas from 13 Chinese patients. After classifying individual cells, we generated a spatial and temporal landscape of glioma that revealed the patterns of invasion between the different sub-regions of gliomas. We also used single-cell inferred CNVs and pseudotime trajectories to inform on the crucial branches that dominate tumor progression. The dynamic cell components of the multi-region biopsy analysis allowed us to spatially deconvolute with unprecedented accuracy the transcriptomic features of the core and those of the periphery of glioma at single cell level. Through this rich and geographically detailed dataset, we were also able to characterize and construct the chemokine and chemokine receptor interactions that exist among different tumor and non-tumor cells. This study provides the first spatial-level analysis of the cellular states that characterize human gliomas. It also presents an initial molecular map of the crosstalks between glioma cells and the surrounding microenvironment with single cell resolution.

genomics↗

bioRxiv2020

Modular and distinct PlexinA4/Farp2/Rac1 signaling controls dendrite morphogenesis

Diverse neuronal populations with distinct cellular morphologies coordinate the complex function of the nervous system. Establishment of distinct neuronal morphologies critically depends on signaling pathways that control axonal and dendritic development. The Sema3A-Nrp1/PlxnA4 signaling pathway promotes cortical neuron basal dendrite arborization but also repels axons. However, the downstream signaling components underlying these disparate functions of Sema3A signaling are unclear. Using the novel PlxnA4KRK-AAA knock-in male and female mice, generated by CRISPR/cas9, we show here that the KRK motif in the PlxnA4 cytoplasmic domain is required for Sema3A-mediated cortical neuron dendritic elaboration but is dispensable for inhibitory axon guidance. The RhoGEF FARP2, which binds to the KRK motif, shows identical functional specificity as the KRK motif in the PlxnA4 receptor. We find that Sema3A activates the small GTPase Rac1, and that Rac1 activity is required for dendrite elaboration but not axon growth cone collapse. This work identifies a novel Sema3A-Nrp1/PlxnA4/FARP2/Rac1 signaling pathway that specifically controls dendritic morphogenesis but is dispensable for repulsive guidance events. Overall, our results demonstrate that the divergent signaling output from multifunctional receptor complexes critically depends on distinct signaling motifs, highlighting the modular nature of guidance cue receptors and its potential to regulate diverse cellular responses. Significance StatementThe proper formation of axonal and dendritic morphologies is crucial for the precise wiring of the nervous system that ultimately leads to the generation of complex functions in an organism. The Semaphorin3A-Neuropilin1/Plexin-A4 signaling pathway has been shown to have multiple key roles in neurodevelopment, from axon repulsion to dendrite elaboration. This study demonstrates that three specific amino acids, the KRK motif within the Plexin-A4 receptor cytoplasmic domain, are required to coordinate the downstream signaling molecules to promote Sema3A-mediated cortical neuron dendritic elaboration, but not inhibitory axon guidance. Our results unravel a novel Semaphorin3A-Plexin-A4 downstream signaling pathway and shed light on how the disparate functions of axon guidance and dendritic morphogenesis are accomplished by the same extracellular ligand in vivo.

neuroscience↗

bioRxiv2020

The origin of domestication genes in goats

Goat domestication was critical for agriculture and civilization, but its underlying genetic changes and selection regimes remain unclear. Here we analyze the genomes of worldwide domestic goats, wild caprid species and historical remains, providing evidence of an ancient introgression event from a West Caucasian tur-like species to the ancestor of domestic goats. One introgressed locus with a strong signature of selection harbors the MUC6 gene which encodes a gastrointestinally secreted mucin. Experiments revealed that the nearly fixed introgressed haplotype confers enhanced immune resistance to gastrointestinal pathogens. Another locus with a strong signal of selection may be related to behavior. The selected alleles at these two loci emerged in domestic goats at least 7,200 and 8,100 years ago, respectively, and increased to high frequencies concurrent with the expansion of the ubiquitous modern mitochondrial haplogroup A. Tracking these archaeologically cryptic evolutionary transformations provides new insights into the mechanism of animal domestication. One Sentence SummaryGoat domestication mainly focused on immune and neural genes, with adaptive leaps driven by introgression and selection.

genomics↗

bioRxiv2020

Capturing volumetric dynamics at high speed in the brain by confocal light field microscopy

Neural network performs complex computations through coordinating collective neural dynamics that are fast and in three-dimensions. Meanwhile, its proper function relies on its 3D supporting environment, including the highly dynamic vascular system that drives energy and material flow. Better understanding of these processes requires methods to capture fast volumetric dynamics in thick tissue. This becomes challenging due to the trade-off between speed and optical sectioning capability in conventional imaging techniques. Here we present a new imaging method, confocal light field microscopy, to enable fast volumetric imaging deep into brain. We demonstrated the power of this method by recording whole brain calcium transients in freely swimming larval zebrafish and observed behaviorally correlated activities on single neurons during its prey capture. Furthermore, we captured neural activities and circulating blood cells over a volume {emptyset} 800 m x 150 m at 70 Hz and up to 600 m deep in the mice brain.

neuroscience↗

bioRxiv2019

NanoCaller for accurate detection of SNPs and small indels from long-read sequencing by deep neural networks

Long-read sequencing enables variant detection in genomic regions that are considered difficult-to-map by short-read sequencing. To fully exploit the benefits of longer reads, here we present a deep-learning method NanoCaller, which detects SNPs using long-range haplotype information, then phases long reads with called SNPs and calls indels with local realignment. Evaluation on 8 human genomes demonstrated that NanoCaller generally achieves better performance than competing approaches. We experimentally validated 41 novel variants in a widely-used benchmarking genome, which cannot be reliably detected previously. In summary, NanoCaller facilitates the discovery of novel variants in complex genomic regions from long- read sequencing.

bioinformatics↗

bioRxiv2019

Dihydroartemisinin-loaded Magnetic Nanoparticles for Enhanced Chemodynamic Therapy

Recently, chemodynamic therapy (CDT) has represented a new approach for cancer treatment with low toxicity and side effects. Nonetheless, it has been a challenge to improve the therapeutic effect through increasing the amount of reactive oxygen species (ROS). Herein, we increased the amount of ROS agents in the Fenton-like reaction by loading dihydroartemisinin (DHA) which was an artemisinin (ART) derivative containing peroxide groups, into magnetic nanoparticles (MNP), thereby improving the therapeutic effect of CDT. Blank MNP were almost non-cytotoxic, whereas three MNP loading ART-based drugs, MNP-ART, MNP-DHA, and MNP-artesunate (MNP-AS), all showed significant killing effect on breast cancer cells (MCF-7 cells), in which MNP-DHA were the most potent. Whats more, the MNP-DHA showed high toxicity to drug-resistant breast cancer cells (MCF-7/ADR cells), demonstrating its ability to overcome multidrug resistance (MDR). The study revealed that MNP could produce ferrous ions under the acidic condition of tumor microenvironment, which catalyzed DHA to produce large amounts of ROS, leading to cell death. Further experiments also showed that the MNP-DHA had significant inhibitory effect on another two aggressive breast cancer cell lines (MDA-MB-231 and MDA-MB-453 cells), which indicated that the great potential of MNP-DHA for the treatment of intractable breast cancers.

bioengineering↗

bioRxiv2019

A novel Arabidopsis phyllosphere resident Protomyces sp. and a re-examination of genus Protomyces based on genome sequence data.

Protomyces is a genus of yeast-like fungi that is currently defined as plant pathogens of only the Umbelliferae (Apiaceae) and Compositae (Asteraceae) family plants. Many Protomyces species have been proposed; however, there is a lack of molecular data and available specimens for Protomyces spp., just over ten species are officially accepted and only six species are preserved and available in public culture collections for examination. Phylogenetic relationships and species boundaries within this genus remain largely controversial. Recently, we isolated Protomyces strains from wild Arabidopsis thaliana (Arabidopsis), a Brassicaceae family plant only distantly related to the accepted Protomyces hosts. We have previously sequenced the genomes of all the currently public available Protomyces species, together with a strain (SC29) we isolated from the Arabidopsis phyllosphere. Genome-wide phylogenetic analysis suggests that SC29 occupies a unique phylogenetic position in the genus Protomyces. The SC29 genome has low average nucleotide identity values in comparison with other species genomes. As physiological evidence, SC29 has morphological characteristics and carbon assimilation patterns that distinguish it from the other six Protomyces species. Analysis with several nuclear gene phylogenetic markers further confirms SC29 as a novel Protomyces species and suggests the act1 gene DNA sequences can be used together with ITS sequences for the rapid identification of Protomyces species. In our previous study, SC29 could persist on the Arabidopsis phyllosphere in both short term laboratory and overwinter outdoor garden experiments and Protomyces spp. (or OTUs) were found in the Arabidopsis phyllosphere at multiple sites in both Finland and Germany. We conclude that SC29 is a novel Protomyces species isolated from Arabidopsis and propose the name of Protomyces arabidopsidicola sp. nov. Additionally, the genus Protomyces may not be strictly associated with only Compositae or Umbelliferae family host plants, as evidenced by SC29 and Protomyces strains previously isolated from plants in other families. The merging of two Protomyces species found to have high genomic similarity (P. inouyei and P. lactucaedebilis) is also proposed.

microbiology↗

bioRxiv2019

Phen2Gene: Rapid Phenotype-Driven Gene Prioritization for Rare Diseases

Human Phenotype Ontology (HPO) terms are increasingly used in diagnostic settings to aid in the characterization of patient phenotypes. The HPO annotation database is updated frequently and can provide detailed phenotype knowledge on various human diseases, and many HPO terms are now mapped to candidate causal genes with binary relationships. To further improve the genetic diagnosis of rare diseases, we incorporated these HPO annotations, gene-disease databases, and gene-gene databases in a probabilistic model to build a novel HPO-driven gene prioritization tool, Phen2Gene. Phen2Gene accesses a database built upon this information called the HPO2Gene Knowledgebase (H2GKB), which provides weighted and ranked gene lists for every HPO term. Phen2Gene is then able to access the H2GKB for patient-specific lists of HPO terms or PhenoPackets descriptions supported by GA4GH (http://phenopackets.org/), calculate a prioritized gene list based on a probabilistic model, and output gene-disease relationships with great accuracy. Phen2Gene outperforms existing gene prioritization tools in speed, and acts as a real-time phenotype driven gene prioritization tool to aid the clinical diagnosis of rare undiagnosed diseases. In addition to a command line tool released under the MIT license (https://github.com/WGLab/Phen2Gene), we also developed a web server and web service (https://phen2gene.wglab.org/) for running the tool via web interface or RESTful API queries. Finally, we have curated a large amount of benchmarking data for phenotype-to-gene tools involving 197 patients across 76 scientific articles and 85 patients de-identified HPO term data from CHOP.

bioinformatics↗

bioRxiv2019

Characterization of Isoforms of the Ovine Granulocyte Colony Stimulating Factor

The granulocyte colony-stimulating factor (GCSF) regulates the maturation, proliferation, and differentiation of precursor cells of neutrophilic granulocytes, and has been widely studied in several species. To investigate the function of variants of sheep GCSF (sGCSF), this study compared difference in their mRNA expression levels. Both the activity and mRNA expression level of GCSFv2 were higher than those of GCSFv1. Their sequences were aligned, which showed that they had the highest homology with bovine GCSF. Then, predicted ovine GCSF isoforms and their constant C-terminals were cloned and expressed, which were stably expressed in mammalian cells. After purification, all GCSF functions were different both in vitro and in vivo, and the GCSF C-terminal was best. These results indicated that the ability to stimulate both the proliferation and differentiation of progenitor cells and to activate the maturation of neutrophils could be used for research of efficacious non-antibiotic protein drugs. Furthermore, GCSF can be used as candidate target of genetic breeding to specifically improve sheep immunity.

genetics↗

bioRxiv2019

Structural variation, functional differentiation and expression characteristics of the AP2/ERF gene family and its response to cold stress and methyl jasmonate in Panax ginseng C.A. Meyer

The APETALA2/Ethylene Responsive Factor (AP2/ERF) gene family has been shown to play a crucial role in plant growth and development, stress responses and secondary metabolite biosynthesis. Nevertheless, little is known about the gene family in ginseng (Panax ginseng), an important traditional medicinal herb in Asia and North America. Here, we report the systematic analysis of the gene family present in ginseng using several transcriptomic databases. A total of 189 putative AP2/ERF genes, defined as PgERF001 through PgERF189. The 93 PgERF genes that have the complete AP2 domain in their open reading frames were classified into five subfamilies, DREB, ERF, AP2, RAV and Soloist. The DREB subfamily and ERF subfamily were further clustered four and six groups, respectively, compared to the 12 groups of these subfamilies found in Arabidopsis. Gene ontology categorized these 397 transcripts of the 189 PgERF genes into eight functional subcategories, suggesting their functional differentiation and they have been especially enriched for the nucleic acid binding transcription factor activity subcategory. The expression activity and networks of the 397 PgERF transcripts have substantially diversified across tissues, developmental stages and genotypes. Then, the expression change of six PgERF genes randomly selected from DREB subfamily, i.e., PgERF073, PgERF079, PgERF110, PgERF115, PgERF120 and PgERF128 responding to cold stress suggesting that DREB subfamily genes played an important role in cold resistance of ginseng. Finally, we studied the responses of the PgERF genes to methyl jasmonate (MeJA). 288 (72.5%) of the 397 PgERF gene transcripts responded to the MeJA treatment, with 136 up-regulated and 152 down-regulated, indicating that most members of the PgERF gene family are responsive to MeJA. These results provide resources and knowledge necessary for family-wide functional analysis of the PgERF genes in ginseng and related species.

genomics↗

bioRxiv2019

Characterizing the Cancer-Associated Microbiome with Small RNA Sequencing Data

The microbiome is recognized as a quasi-organ in the human body. In particular, the gut microbiome is correlated with immune function, metabolism, and tumorigenesis. When dysbiosis of the microbiome occurs, this variation may contribute to alterations in the microenvironment, potentially inducing an inflammatory immune response and providing a niche for neoplastic growth. However, there is limited evidence regarding the correlation and interaction between the microbiome and tumorigenesis. By utilizing microRNA sequencing data of patients with colon and rectal cancer from The Cancer Genome Atlas, we designed a novel analytical process to extract non-human small RNA sequences and align them with the microbial genome to obtain a comprehensive view of the cancer-associated microbiome. In the present study, we identified > 1000 genera among 630 colorectal samples and clustered these samples into three distinctive colorectal enterotypes. Each cluster has its own distinctive microbial composition and interactions. Furthermore, we found 12 genera from these clusters that are associated with cancer stages and revealed their putative functions. Our results indicate that the proposed analytical approach can effectively determine the cancer-associated microbiome. It may be readily applied to explore other types of cancer, in which specimens of the microbiome are difficult to collect.

bioinformatics↗