Volume II: Computational Solutions for Microbiome and Metagenomics Sequencing Analyses

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u Zhang","firstName":null,"middleName":null,"lastName":null,"image":{"height":null,"url":"https://loop.frontiersin.org/images/profile/805897/70","width":null,"caption":null},"loopProfileUrl":"https://loop.frontiersin.org/people/805897/overview","affiliation":{"name":"School of Medicine","address":null},"affiliations":[{"name":"School of Medicine","address":null}],"nessieId":"120259735368"},{"fullName":"Yanjie Wei","firstName":null,"middleName":null,"lastName":null,"image":{"height":null,"url":"https://loop.frontiersin.org/images/profile/90804/70","width":null,"caption":null},"loopProfileUrl":"https://loop.frontiersin.org/people/90804/overview","affiliation":{"name":"Centre for High Performance Computing","address":null},"affiliations":[{"name":"Centre for High Performance Computing","address":null},{"name":"Shenzhen Institutes of Advanced Technology","address":null}],"nessieId":"51540259639"}],"dates":{"acceptedDate":"2023-07-07","recentDate":"2023-07-17"},"doi":"10.3389/fmolb.2023.1253303","frontiersExtra":{"articleType":"Editorial","impact":{"citations":0,"crossrefCitations":0,"downloads":561,"frontiersViews":0,"pmcDownloads":0,"pmcViews":0,"scopusCitations":0,"views":3131},"isPartOfResearchTopic":true,"isPublished":true,"section":"Molecular Diagnostics and Therapeutics"},"guid":1253303,"images":null,"journal":{"guid":698,"name":"Frontiers in Molecular Biosciences","link":null,"nessieId":null,"palette":null,"publisher":"Frontiers Media","images":null,"isOnline":null,"isDeleted":null,"isDisabled":null,"issn":null},"link":"https://www.frontiersin.org/articles/10.3389/fmolb.2023.1253303","pubDate":"2023-07-17","score":13.956626859110443,"title":"Editorial: Computational solutions for microbiome and metagenomics sequencing analyses, Volume II","topics":["machine learning","Gut Microbiota","Feature Selection","Immune markers","Metagenomics sequencing","COVID-19","circular RNA biomarkers"],"pdfUrl":"https://www.frontiersin.org/articles/10.3389/fmolb.2023.1253303/pdf"},{"__typename":"Feed_Article","_id":"680951a40631c3389bc5249f","abstract":"Background: IgA nephropathy (IgAN) is the most common type of glomerulonephritis in Asia. Its pathogenesis involves higher expression of galactose-deficient IgA1 (Gd-IgA1) and dysregulated intestinal mucosal immunity. The objective of this study was to explore whether specific gut microbiota and associated enzymes affect Gd-IgA1 in IgAN.Methods: This study carried out shotgun metagenomic sequencing with Illumina on fecal samples collected from 20 IgAN patients (IgAN group) and 20 healthy controls (HCs group) who were recruited from January 2016 to December 2018 at the Second Clinical College of Guangzhou University of Chinese Medicine. Differences analysis in gut microbiota was performed to determine the overall microbiota composition, the representative enterotypes, and the microbiota abundance. Correlations between gut microbiota and clinical indicators were assessed by Spearman’s analysis. Moreover, the functional prediction of microbial communities and the quantitative calculation of enzymes encoded by microbiome were performed using the MetaCyc pathway and the bioBakery three platform, respectively.Results:Bacteroides plebeius and Bacteroides vulgatus levels were higher, while Prevotella copri and Alistipes putredinis levels were lower in the IgAN group compared to HCs group. Enterotype I characterized by Bacteroides was closely related to the IgAN patients. Moreover, Bacteroides fragilis, Flavonifractor plautii and Ruminococcus gnavus were characteristic bacteria enriched in IgAN patients. Spearman’s correlation analysis found that Eggerthella lenta and Ruminococcus bromii were positively correlated with urine protein-creatinine ratio, while Ruminococcus gnavus showed a direct association with red blood cells in urine, and Bacteroides vulgatus and Ruminococcus gnavus were positively correlated with eGFR. These results indicated that intestinal dysbacteriosis occurred in IgAN patients and was associated with clinical and biochemical features. In addition, MetaCyc pathway analysis predicted microbiota-related metabolic pathways, including the biosynthesis of amino acids and glycans, were associated with the IgAN group. Microbial enzymes analysis highlighted that Gd-IgA1-associated α-galactosidase and α-N-acetyl-galactosaminidase secreted by Flavonifractor plautii were enriched in IgAN patients.Conclusion: These findings suggested that α-galactosidase and α-N-acetyl-galactosaminidase secreted by Flavonifractor plautii might be related to the production of Gd-IgA1, indicating that enzymes originated from abnormal intestinal microbiota may contribute to the production of Gd-IgA1 and play an important role in the pathogenesis of IgAN.","htmlAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e IgA nephropathy (IgAN) is the most common type of glomerulonephritis in Asia. Its pathogenesis involves higher expression of galactose-deficient IgA1 (Gd-IgA1) and dysregulated intestinal mucosal immunity. The objective of this study was to explore whether specific gut microbiota and associated enzymes affect Gd-IgA1 in IgAN.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e This study carried out shotgun metagenomic sequencing with Illumina on fecal samples collected from 20 IgAN patients (IgAN group) and 20 healthy controls (HCs group) who were recruited from January 2016 to December 2018 at the Second Clinical College of Guangzhou University of Chinese Medicine. Differences analysis in gut microbiota was performed to determine the overall microbiota composition, the representative enterotypes, and the microbiota abundance. Correlations between gut microbiota and clinical indicators were assessed by Spearman’s analysis. Moreover, the functional prediction of microbial communities and the quantitative calculation of enzymes encoded by microbiome were performed using the MetaCyc pathway and the bioBakery three platform, respectively.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e \u003cem\u003eBacteroides plebeius\u003c/em\u003e and \u003cem\u003eBacteroides vulgatus\u003c/em\u003e levels were higher, while \u003cem\u003ePrevotella copri\u003c/em\u003e and \u003cem\u003eAlistipes putredinis\u003c/em\u003e levels were lower in the IgAN group compared to HCs group. Enterotype I characterized by \u003cem\u003eBacteroides\u003c/em\u003e was closely related to the IgAN patients. Moreover, \u003cem\u003eBacteroides fragilis\u003c/em\u003e, \u003cem\u003eFlavonifractor plautii\u003c/em\u003e and \u003cem\u003eRuminococcus gnavus\u003c/em\u003e were characteristic bacteria enriched in IgAN patients. Spearman’s correlation analysis found that \u003cem\u003eEggerthella lenta\u003c/em\u003e and \u003cem\u003eRuminococcus bromii\u003c/em\u003e were positively correlated with urine protein-creatinine ratio, while \u003cem\u003eRuminococcus gnavus\u003c/em\u003e showed a direct association with red blood cells in urine, and \u003cem\u003eBacteroides vulgatus\u003c/em\u003e and \u003cem\u003eRuminococcus gnavus\u003c/em\u003e were positively correlated with eGFR. These results indicated that intestinal dysbacteriosis occurred in IgAN patients and was associated with clinical and biochemical features. In addition, MetaCyc pathway analysis predicted microbiota-related metabolic pathways, including the biosynthesis of amino acids and glycans, were associated with the IgAN group. Microbial enzymes analysis highlighted that Gd-IgA1-associated α-galactosidase and α-N-acetyl-galactosaminidase secreted by \u003cem\u003eFlavonifractor plautii\u003c/em\u003e were enriched in IgAN patients.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e These findings suggested that α-galactosidase and α-N-acetyl-galactosaminidase secreted by \u003cem\u003eFlavonifractor plautii\u003c/em\u003e might be related to the production of Gd-IgA1, indicating that enzymes originated from abnormal intestinal microbiota may contribute to the production of Gd-IgA1 and play an important role in the pathogenesis of IgAN.\u003c/p\u003e","authors":[{"fullName":"Xiaolin Liang","firstName":null,"middleName":null,"lastName":null,"image":{"height":null,"url":"https://loop.frontiersin.org/images/profile/1959766/70","width":null,"caption":null},"loopProfileUrl":"https://loop.frontiersin.org/people/1959766/overview","affiliation":{"name":"The Second Clinical College of Guangzhou University of Chinese Medicine","address":null},"affiliations":[{"name":"The Second Clinical College of Guangzhou University of Chinese Medicine","address":null}],"nessieId":"352187978657"},{"fullName":"Simeng Zhang","firstName":null,"middleName":null,"lastName":null,"image":{"height":null,"url":"https://loop.frontiersin.org/images/profile/1952512/70","width":null,"caption":null},"loopProfileUrl":"https://loop.frontiersin.org/people/1952512/overview","affiliation":{"name":"The Second Clinical College of Guangzhou University of Chinese Medicine","address":null},"affiliations":[{"name":"The Second Clinical College of Guangzhou University of Chinese Medicine","address":null}],"nessieId":null},{"fullName":"Difei Zhang","firstName":null,"middleName":null,"lastName":null,"image":{"height":null,"url":"https://loop.frontiersin.org/images/profile/1481639/70","width":null,"caption":null},"loopProfileUrl":"https://loop.frontiersin.org/people/1481639/overview","affiliation":{"name":"The Second Clinical College of Guangzhou University of Chinese Medicine","address":null},"affiliations":[{"name":"The Second Clinical College of Guangzhou University of Chinese Medicine","address":null},{"name":"Department of Nephrology","address":null},{"name":"Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research","address":null}],"nessieId":"317828231528"},{"fullName":"Liang Hu","firstName":null,"middleName":null,"lastName":null,"image":{"height":null,"url":"https://loop.frontiersin.org/images/profile/1959851/70","width":null,"caption":null},"loopProfileUrl":"https://loop.frontiersin.org/people/1959851/overview","affiliation":{"name":"The Second Clinical College of Guangzhou University of Chinese Medicine","address":null},"affiliations":[{"name":"The Second Clinical College of Guangzhou University of Chinese Medicine","address":null},{"name":"Hunan Academy of Traditional Chinese Medicine Affiliated 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Medicine","address":null},"affiliations":[{"name":"The Second Clinical College of Guangzhou University of Chinese Medicine","address":null},{"name":"Department of Nephrology","address":null}],"nessieId":"60130118607"},{"fullName":"Yuan Xu","firstName":null,"middleName":null,"lastName":null,"image":{"height":null,"url":"https://loop.frontiersin.org/images/profile/1959992/70","width":null,"caption":null},"loopProfileUrl":"https://loop.frontiersin.org/people/1959992/overview","affiliation":{"name":"The Second Clinical College of Guangzhou University of Chinese Medicine","address":null},"affiliations":[{"name":"The Second Clinical College of Guangzhou University of Chinese Medicine","address":null},{"name":"Department of Nephrology","address":null}],"nessieId":"42950304108"},{"fullName":"Haijing Hou","firstName":null,"middleName":null,"lastName":null,"image":{"height":null,"url":"https://loop.frontiersin.org/images/profile/1562756/70","width":null,"caption":null},"loopProfileUrl":"https://loop.frontiersin.org/people/1562756/overview","affiliation":{"name":"The Second Clinical College of Guangzhou University of Chinese Medicine","address":null},"affiliations":[{"name":"The Second Clinical College of Guangzhou University of Chinese Medicine","address":null},{"name":"Department of Nephrology","address":null},{"name":"Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research","address":null}],"nessieId":"85899982558"},{"fullName":"Chuan Zou","firstName":null,"middleName":null,"lastName":null,"image":{"height":null,"url":"https://loop.frontiersin.org/images/profile/648544/70","width":null,"caption":null},"loopProfileUrl":"https://loop.frontiersin.org/people/648544/overview","affiliation":{"name":"The Second Clinical College of Guangzhou University of Chinese Medicine","address":null},"affiliations":[{"name":"The Second Clinical College of Guangzhou University of Chinese Medicine","address":null},{"name":"Department of Nephrology","address":null},{"name":"Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research","address":null}],"nessieId":"171799355734"},{"fullName":"Xusheng Liu","firstName":null,"middleName":null,"lastName":null,"image":{"height":null,"url":"https://loop.frontiersin.org/images/profile/1136057/70","width":null,"caption":null},"loopProfileUrl":"https://loop.frontiersin.org/people/1136057/overview","affiliation":{"name":"The Second Clinical College of Guangzhou University of Chinese Medicine","address":null},"affiliations":[{"name":"The Second Clinical College of Guangzhou University of Chinese Medicine","address":null},{"name":"Department of Nephrology","address":null},{"name":"Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research","address":null}],"nessieId":"17180523118"},{"fullName":"Yang Chen","firstName":null,"middleName":null,"lastName":null,"image":{"height":null,"url":"https://loop.frontiersin.org/images/profile/571397/70","width":null,"caption":null},"loopProfileUrl":"https://loop.frontiersin.org/people/571397/overview","affiliation":{"name":"The Second Clinical College of Guangzhou University of Chinese Medicine","address":null},"affiliations":[{"name":"The Second Clinical College of Guangzhou University of Chinese Medicine","address":null},{"name":"Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research","address":null}],"nessieId":"214749018036"},{"fullName":"Fuhua Lu","firstName":null,"middleName":null,"lastName":null,"image":{"height":null,"url":"https://loop.frontiersin.org/images/profile/1469739/70","width":null,"caption":null},"loopProfileUrl":"https://loop.frontiersin.org/people/1469739/overview","affiliation":{"name":"The Second Clinical College of Guangzhou University of Chinese Medicine","address":null},"affiliations":[{"name":"The Second Clinical College of Guangzhou University of Chinese Medicine","address":null},{"name":"Department of Nephrology","address":null},{"name":"Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research","address":null}],"nessieId":"51540259445"}],"dates":{"acceptedDate":"2022-08-09","recentDate":"2022-08-24"},"doi":"10.3389/fmolb.2022.970723","frontiersExtra":{"articleType":"Original Research","impact":{"citations":10,"crossrefCitations":0,"downloads":1751,"frontiersViews":0,"pmcDownloads":0,"pmcViews":0,"scopusCitations":0,"views":4470},"isPartOfResearchTopic":true,"isPublished":true,"section":"Molecular Diagnostics and Therapeutics"},"guid":970723,"images":[{"height":400,"url":"https://www.frontiersin.org/files/myhome article library/970723/970723_Thumb_400.jpg","width":401,"caption":null},{"height":632,"url":"https://www.frontiersin.org/files/Articles/970723/fmolb-09-970723-HTML/image_m/fmolb-09-970723-g001.jpg","width":830,"caption":"Community Profiling analysis showing differential relative abundances of fecal microbiota in IgAN patients and HCs. (A) Microbiome composition of the two groups at the genus level. (B) Microbiome composition of the two groups at the species level. (C) Relative abundance of the top 10 species in each sample."},{"height":797,"url":"https://www.frontiersin.org/files/Articles/970723/fmolb-09-970723-HTML/image_m/fmolb-09-970723-g002.jpg","width":1017,"caption":"Rarefaction curves and comparison of diversity indexes between IgAN patients and HCs. (A) Rarefaction curves of patients with IgAN and HCs at the species level. The sequencing depth was judged to be sufficient as the curve tended to be flat. The detection rate of the microbial community was almost flat, revealing a reasonable sequencing volume that could cover most species. (B) α-diversity indexes in IgAN patients and HCs (observed, diversity Shannon and Simpson indexes depict diversity; pielou, evenness Simpson and Gini depict evenness; camargo, dbp and core abundance depict dominance). (C) PcoA for β-diversity analysis. Green and red represent different samples from the two groups. The structure and composition of the gut microbiota in patients with IgAN were not significantly different from those of HCs. (D) Venn diagram. There were 71 species shared between the two groups, while 13 species were specific to HCs and 7 species were specific to IgAN patients."},{"height":814,"url":"https://www.frontiersin.org/files/Articles/970723/fmolb-09-970723-HTML/image_m/fmolb-09-970723-g003.jpg","width":830,"caption":"Analysis of Enterotypes between IgAN patients and HCs. (A) A PCA plot indicating that enterotypes driven by Bacteroides and Prevotella were dominants in IgAN and HCs groups, respectively. (B) Frequency of enterotypes in both groups. (C) Abundance of Bacteroides and Prevotella between the two groups showed an opposite trend."},{"height":598,"url":"https://www.frontiersin.org/files/Articles/970723/fmolb-09-970723-HTML/image_m/fmolb-09-970723-g004.jpg","width":1072,"caption":"Gut microbiota differences from phylum to species between patients with IgAN and HCs. (A) Microbiome biomarkers were identified using a logarithmic linear discriminant analysis (LDA) effect size (LefSe) threshold \u003e4.0. (B) HeatTree for clustering analysis. Red indicates a significant increase in abundance in IgAN patients compared to the HCs, while blue depicts the opposite. (C) Co-occurrence network analysis of stool microbiota using Pearson’s correlation coefficient. A node represents a species. The node size indicates the level of abundance. Color scale indicates the proportion of bacterium in the two groups separately. Red depicts IgAN patients while green depicts HCs. Connecting lines indicate the strength of the relationship. (D) Correlation coefficient rank at the genus level. Red denotes positive associations in IgAN patients, while blue denotes negative associations. The legend on the right indicates the abundance of the bacterium in both groups, with red indicating high and blue indicating low abundance (c = class; o = order; f = family; g = genera; s = species)."},{"height":698,"url":"https://www.frontiersin.org/files/Articles/970723/fmolb-09-970723-HTML/image_m/fmolb-09-970723-g005.jpg","width":699,"caption":"Heatmaps showing correlations between gut microbiota species and IgAN clinical parameters. The intensity of the color indicates the r value (correlation). The red color represents a positive score, and the blue color represents a negative one. *p \u003c0.05 and **p \u003c0.01."},{"height":450,"url":"https://www.frontiersin.org/files/Articles/970723/fmolb-09-970723-HTML/image_m/fmolb-09-970723-g006.jpg","width":1072,"caption":"Enrichment of functional pathways of differential bacteria between IgAN patients and HCs. (A) The distribution of LDA values for different pathways in IgAN and HCs samples. (B) Relative contribution of gut microbes to pathways IgAN patients. (C) Relative contribution of gut microbes to pathways in HCs samples. Enrichment was defined as p \u003c 0.05, q \u003c0.1 and LDA\u003e3.0."},{"height":731,"url":"https://www.frontiersin.org/files/Articles/970723/fmolb-09-970723-HTML/image_m/fmolb-09-970723-g007.jpg","width":955,"caption":"The enrichment of active enzymes and their corresponding specific bacteria. (A) Enzymes enriched by gut flora in IgAN patients and HCs. (B) The relative abundance of β-galactosidase, β-N-acetylhexosaminidase, α-galactosidase and α-N-acetylgalactosaminidase between the IgAN group and HCs. (C) The stratification of various bacteria for β-galactosidase, β-N-acetylhexosaminidase, α-galactosidase and α-N-acetylgalactosaminidase."}],"journal":{"guid":698,"name":"Frontiers in Molecular Biosciences","link":null,"nessieId":null,"palette":null,"publisher":"Frontiers Media","images":null,"isOnline":null,"isDeleted":null,"isDisabled":null,"issn":null},"link":"https://www.frontiersin.org/articles/10.3389/fmolb.2022.970723","pubDate":"2022-08-24","score":28.46215839988261,"title":"Metagenomics-based systematic analysis reveals that gut microbiota Gd-IgA1-associated enzymes may play a key role in IgA nephropathy","topics":["Gut Microbiota","α-galactosidase","immunoglobulin a nephropathy","Galactose-deficient IgA1","α-N-Acetyl-galactosaminidase","Flavonifractor plautii","metagenomics sequencing."],"pdfUrl":"https://www.frontiersin.org/articles/10.3389/fmolb.2022.970723/pdf"},{"__typename":"Feed_Article","_id":"680951a40631c3389bc5249e","abstract":"Short-chain fatty acids (SCFAs) including acetate, formate, propionate, and butyrate are the end products of dietary fiber and host glycan fermentation by the human gut microbiota (HGM). SCFAs produced in the column are of utmost importance for host physiology and health. Butyrate and propionate improve gut health and play a key role in the neuroendocrine and immune systems. Prediction of HGM metabolic potential is important for understanding the influence of diet and HGM-produced metabolites on human health. We conducted a detailed metabolic reconstruction of pathways for the synthesis of SCFAs and L- and D-lactate, as additional fermentation products, in a reference set of 2,856 bacterial genomes representing strains of \u003e800 known HGM species. The reconstructed butyrate and propionate pathways included four and three pathway variants, respectively, that start from different metabolic precursors. Altogether, we identified 48 metabolic enzymes, including five alternative enzymes in propionate pathways, and propagated their occurrences across all studied genomes. We established genomic signatures for reconstructed pathways and classified genomes according to their simplified binary phenotypes encoding the ability (“1”) or inability (“0”) of a given organism to produce SCFAs. The resulting binary phenotypes combined into a binary phenotype matrix were used to assess the SCFA synthesis potential of HGM samples from several public metagenomic studies. We report baseline and variance for Community Phenotype Indices calculated for SCFAs production capabilities in 16S metagenomic samples of intestinal microbiota from two large national cohorts (American Gut Project, UK twins), the Hadza hunter-gatherers, and the young children cohort of infants with high-risk for type 1 diabetes. We further linked the predicted SCFA metabolic capabilities with available SCFA concentrations both for in vivo fecal samples and in vitro fermentation samples from previous studies. Finally, we analyzed differential representation of individual SCFA pathway genes across several WGS metagenomic datasets. The obtained collection of SCFA pathway genes and phenotypes enables the predictive metabolic phenotype profiling of HGM datasets and enhances the in silico methodology to study cross-feeding interactions in the gut microbiomes.","htmlAbstract":"\u003cp\u003eShort-chain fatty acids (SCFAs) including acetate, formate, propionate, and butyrate are the end products of dietary fiber and host glycan fermentation by the human gut microbiota (HGM). SCFAs produced in the column are of utmost importance for host physiology and health. Butyrate and propionate improve gut health and play a key role in the neuroendocrine and immune systems. Prediction of HGM metabolic potential is important for understanding the influence of diet and HGM-produced metabolites on human health. We conducted a detailed metabolic reconstruction of pathways for the synthesis of SCFAs and L- and D-lactate, as additional fermentation products, in a reference set of 2,856 bacterial genomes representing strains of \u0026gt;800 known HGM species. The reconstructed butyrate and propionate pathways included four and three pathway variants, respectively, that start from different metabolic precursors. Altogether, we identified 48 metabolic enzymes, including five alternative enzymes in propionate pathways, and propagated their occurrences across all studied genomes. We established genomic signatures for reconstructed pathways and classified genomes according to their simplified binary phenotypes encoding the ability (“1”) or inability (“0”) of a given organism to produce SCFAs. The resulting binary phenotypes combined into a binary phenotype matrix were used to assess the SCFA synthesis potential of HGM samples from several public metagenomic studies. We report baseline and variance for Community Phenotype Indices calculated for SCFAs production capabilities in 16S metagenomic samples of intestinal microbiota from two large national cohorts (American Gut Project, UK twins), the Hadza hunter-gatherers, and the young children cohort of infants with high-risk for type 1 diabetes. We further linked the predicted SCFA metabolic capabilities with available SCFA concentrations both for \u003cem\u003ein vivo\u003c/em\u003e fecal samples and \u003cem\u003ein vitro\u003c/em\u003e fermentation samples from previous studies. Finally, we analyzed differential representation of individual SCFA pathway genes across several WGS metagenomic datasets. The obtained collection of SCFA pathway genes and phenotypes enables the predictive metabolic phenotype profiling of HGM datasets and enhances the \u003cem\u003ein silico\u003c/em\u003e methodology to study cross-feeding interactions in the gut microbiomes.\u003c/p\u003e","authors":[{"fullName":"Maria S. Frolova","firstName":null,"middleName":null,"lastName":null,"image":{"height":null,"url":"https://loop.frontiersin.org/images/profile/1921605/70","width":null,"caption":null},"loopProfileUrl":"https://loop.frontiersin.org/people/1921605/overview","affiliation":{"name":"Institute of Cell Biophysics","address":null},"affiliations":[{"name":"Institute of Cell Biophysics","address":null}],"nessieId":"730145094301"},{"fullName":"Inna A. Suvorova","firstName":null,"middleName":null,"lastName":null,"image":{"height":null,"url":"https://loop.frontiersin.org/images/profile/653331/70","width":null,"caption":null},"loopProfileUrl":"https://loop.frontiersin.org/people/653331/overview","affiliation":{"name":"A.A. Kharkevich Institute for Information Transmission Problems","address":null},"affiliations":[{"name":"A.A. Kharkevich Institute for Information Transmission Problems","address":null}],"nessieId":"214749014227"},{"fullName":"Stanislav N. Iablokov","firstName":null,"middleName":null,"lastName":null,"image":{"height":null,"url":"https://loop.frontiersin.org/images/profile/667693/70","width":null,"caption":null},"loopProfileUrl":"https://loop.frontiersin.org/people/667693/overview","affiliation":{"name":"A.A. Kharkevich Institute for Information Transmission Problems","address":null},"affiliations":[{"name":"A.A. Kharkevich Institute for Information Transmission Problems","address":null}],"nessieId":"154619470604"},{"fullName":"Sergei N. Petrov","firstName":null,"middleName":null,"lastName":null,"image":null,"loopProfileUrl":null,"affiliation":{"name":"Vavilov Institute of General Genetics","address":null},"affiliations":[{"name":"Vavilov Institute of General Genetics","address":null}],"nessieId":null},{"fullName":"Dmitry A. Rodionov","firstName":null,"middleName":null,"lastName":null,"image":{"height":null,"url":"https://loop.frontiersin.org/images/profile/78772/70","width":null,"caption":null},"loopProfileUrl":"https://loop.frontiersin.org/people/78772/overview","affiliation":{"name":"Sanford Burnham Prebys Medical Discovery Institute","address":null},"affiliations":[{"name":"Sanford Burnham Prebys Medical Discovery Institute","address":null}],"nessieId":"214749011382"}],"dates":{"acceptedDate":"2022-07-19","recentDate":"2022-08-11"},"doi":"10.3389/fmolb.2022.949563","frontiersExtra":{"articleType":"Original Research","impact":{"citations":59,"crossrefCitations":0,"downloads":600,"frontiersViews":0,"pmcDownloads":0,"pmcViews":0,"scopusCitations":0,"views":10799},"isPartOfResearchTopic":true,"isPublished":true,"section":"Molecular Diagnostics and Therapeutics"},"guid":949563,"images":[{"height":219,"url":"https://www.frontiersin.org/files/myhome article library/949563/949563_Thumb_400.jpg","width":400,"caption":null},{"height":878,"url":"https://www.frontiersin.org/files/Articles/949563/fmolb-09-949563-HTML/image_m/fmolb-09-949563-g001.jpg","width":1065,"caption":"Reconstructed metabolic pathways of SCFA synthesis in reference HGM genomes. (A) Butyrate synthesis, (B) Propionate synthesis, (C) Acetate, Formate and Lactate synthesis. Enzymes are shown by colored boxes with indicated Enzyme Commission (EC) numbers with detailed functional roles described in Supplementary Table S1. Alternative biochemical pathways for butyrate and propionate synthesis are highlighted by different colors. Shared biochemical routes for conversion of crotonoyl-CoA to butyrate are in dark brown boxes. Central carbon metabolism metabolites and amino acids serving as substrates for acid fermentation pathways are circled; final fermentation products are in red.."},{"height":356,"url":"https://www.frontiersin.org/files/Articles/949563/fmolb-09-949563-HTML/image_m/fmolb-09-949563-g002.jpg","width":865,"caption":"Distribution of Community Phenotype Indices (CPI) for SCFAs and lactate in HGM 16S samples from AGP, UKT and Hadza datasets. Box plots with the median values show distribution of CPI values calculated for each 16S sample. Each CPI value corresponds to the relative abundance of bacterial 16S reads possessing predicted metabolic capability to produce a SCFA."},{"height":654,"url":"https://www.frontiersin.org/files/Articles/949563/fmolb-09-949563-HTML/image_m/fmolb-09-949563-g003.jpg","width":1052,"caption":"Relationship between Community Phenotype Indices (CPI) and Alpha Diversity (AD) for the UKT dataset. Samples are grouped together based on their AD values calculated using Faith phylogenetic diversity metric."},{"height":468,"url":"https://www.frontiersin.org/files/Articles/949563/fmolb-09-949563-HTML/image_m/fmolb-09-949563-g004.jpg","width":858,"caption":"Distribution of Community Phenotype Indices (CPI) for SCFAs and lactate in HGM 16S samples from the TEDDY dataset among two age groups of children."},{"height":1000,"url":"https://www.frontiersin.org/files/Articles/949563/fmolb-09-949563-HTML/image_m/fmolb-09-949563-g005.jpg","width":1065,"caption":"Linear discriminant analysis with effect size (LEfSe) for butyrate producers in HGM samples from young children of different age groups in the TEDDY study. (A) The LEfSe analysis was performed on taxonomic abundances of Amplicon Sequence Variants (ASVs) representing predicted butyrate producers in each sample. LDA score plot includes top taxonomic species corresponding to the most discriminative butyrate producers between two age groups of children. (B) and (C) Boxplots of relative abundances of the most dominant butyrate producing species in HGM samples from children in different age groups."},{"height":1056,"url":"https://www.frontiersin.org/files/Articles/949563/fmolb-09-949563-HTML/image_m/fmolb-09-949563-g006.jpg","width":740,"caption":"Correlations between Community Phenotype Indices (CPI) for butyrate and propionate production and the experimentally measured concentrations of SCFAs in 16S metagenomics studies of HGM. (A) In vivo study of the effects of dietary fibers on fecal microbiota of 200 healthy individuals (Deehan et al., 2020). (B) In vitro batch fermentation study of the effect of fibers on HGM microbiota (Chen M. et al., 2020). (C) Study of the effects of dietary emulsifiers on fecal microbiota in vitro (Elmén et al., 2020)."},{"height":614,"url":"https://www.frontiersin.org/files/Articles/949563/fmolb-09-949563-HTML/image_m/fmolb-09-949563-g007.jpg","width":1059,"caption":"Distribution of metagenomic abundances for SCFA synthesis pathways in HGM samples from TEDDY (A) and IBD (B) datasets. Pathway abundances were calculated as a sum of TMM-normalized counts for selected signature genes in each SCFA pathway (see Supplementary Table S6)."},{"height":571,"url":"https://www.frontiersin.org/files/Articles/949563/fmolb-09-949563-HTML/image_m/fmolb-09-949563-g008.jpg","width":969,"caption":"Metabolic pathways and cross-feeding mechanisms for SCFA production by HGM bacteria. Terminal SCFAs and lactate are in green. Dietary nutrients and core metabolic precursors are in black and red, respectively. Microbial SCFA fermentation pathways analyzed in this work are shown by red arrows. Carbohydrate catabolic pathways are in black. Wood-Ljungdahl pathway is in blue. Absorption of terminal SCFAs by intestinal epithelial cells is shown by thick green arrows. Cross-feeding interactions between HGM members are shown by thick orange arrows."}],"journal":{"guid":698,"name":"Frontiers in Molecular Biosciences","link":null,"nessieId":null,"palette":null,"publisher":"Frontiers Media","images":null,"isOnline":null,"isDeleted":null,"isDisabled":null,"issn":null},"link":"https://www.frontiersin.org/articles/10.3389/fmolb.2022.949563","pubDate":"2022-08-11","score":103.45820206608504,"title":"Genomic reconstruction of short-chain fatty acid production by the human gut microbiota","topics":["gut microbiome","metabolic pathway","Metagenomic","propionate","Metabolic phenotype","butyrate synthesis"],"pdfUrl":"https://www.frontiersin.org/articles/10.3389/fmolb.2022.949563/pdf"},{"__typename":"Feed_Article","_id":"680951a40631c3389bc5249a","abstract":"Notably, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a tight relationship with the immune system. Human resistance to COVID-19 infection comprises two stages. The first stage is immune defense, while the second stage is extensive inflammation. This process is further divided into innate and adaptive immunity during the immune defense phase. These two stages involve various immune cells, including CD4+ T cells, CD8+ T cells, monocytes, dendritic cells, B cells, and natural killer cells. Various immune cells are involved and make up the complex and unique immune system response to COVID-19, providing characteristics that set it apart from other respiratory infectious diseases. In the present study, we identified cell markers for differentiating COVID-19 from common inflammatory responses, non-COVID-19 severe respiratory diseases, and healthy populations based on single-cell profiling of the gene expression of six immune cell types by using Boruta and mRMR feature selection methods. Some features such as IFI44L in B cells, S100A8 in monocytes, and NCR2 in natural killer cells are involved in the innate immune response of COVID-19. Other features such as ZFP36L2 in CD4+ T cells can regulate the inflammatory process of COVID-19. Subsequently, the IFS method was used to determine the best feature subsets and classifiers in the six immune cell types for two classification algorithms. Furthermore, we established the quantitative rules used to distinguish the disease status. The results of this study can provide theoretical support for a more in-depth investigation of COVID-19 pathogenesis and intervention strategies.","htmlAbstract":"\u003cp\u003eNotably, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a tight relationship with the immune system. Human resistance to COVID-19 infection comprises two stages. The first stage is immune defense, while the second stage is extensive inflammation. This process is further divided into innate and adaptive immunity during the immune defense phase. These two stages involve various immune cells, including CD4\u003csup\u003e+\u003c/sup\u003e T cells, CD8\u003csup\u003e+\u003c/sup\u003e T cells, monocytes, dendritic cells, B cells, and natural killer cells. Various immune cells are involved and make up the complex and unique immune system response to COVID-19, providing characteristics that set it apart from other respiratory infectious diseases. In the present study, we identified cell markers for differentiating COVID-19 from common inflammatory responses, non-COVID-19 severe respiratory diseases, and healthy populations based on single-cell profiling of the gene expression of six immune cell types by using Boruta and mRMR feature selection methods. Some features such as IFI44L in B cells, S100A8 in monocytes, and NCR2 in natural killer cells are involved in the innate immune response of COVID-19. Other features such as ZFP36L2 in CD4\u003csup\u003e+\u003c/sup\u003e T cells can regulate the inflammatory process of COVID-19. Subsequently, the IFS method was used to determine the best feature subsets and classifiers in the six immune cell types for two classification algorithms. Furthermore, we established the quantitative rules used to distinguish the disease status. The results of this study can provide theoretical support for a more in-depth investigation of COVID-19 pathogenesis and intervention strategies.\u003c/p\u003e","authors":[{"fullName":"Hao Li","firstName":null,"middleName":null,"lastName":null,"image":{"height":null,"url":"https://loop.frontiersin.org/images/profile/947781/70","width":null,"caption":null},"loopProfileUrl":"https://loop.frontiersin.org/people/947781/overview","affiliation":{"name":"College of Biological and Food Engineering","address":null},"affiliations":[{"name":"College of Biological and Food Engineering","address":null}],"nessieId":"146029536994"},{"fullName":"Feiming Huang","firstName":null,"middleName":null,"lastName":null,"image":{"height":null,"url":"https://loop.frontiersin.org/images/profile/1529552/70","width":null,"caption":null},"loopProfileUrl":"https://loop.frontiersin.org/people/1529552/overview","affiliation":{"name":"School of Life Sciences","address":null},"affiliations":[{"name":"School of Life Sciences","address":null}],"nessieId":null},{"fullName":"Huiping Liao","firstName":null,"middleName":null,"lastName":null,"image":null,"loopProfileUrl":null,"affiliation":{"name":"Ophthalmology and Optometry Medical School","address":null},"affiliations":[{"name":"Ophthalmology and Optometry Medical School","address":null}],"nessieId":null},{"fullName":"Zhandong Li","firstName":null,"middleName":null,"lastName":null,"image":{"height":null,"url":"https://loop.frontiersin.org/images/profile/928572/70","width":null,"caption":null},"loopProfileUrl":"https://loop.frontiersin.org/people/928572/overview","affiliation":{"name":"College of Biological and Food Engineering","address":null},"affiliations":[{"name":"College of Biological and Food Engineering","address":null}],"nessieId":"8590583466"},{"fullName":"Kaiyan Feng","firstName":null,"middleName":null,"lastName":null,"image":{"height":null,"url":"https://loop.frontiersin.org/images/profile/777635/70","width":null,"caption":null},"loopProfileUrl":"https://loop.frontiersin.org/people/777635/overview","affiliation":{"name":"Department of Computer Science","address":null},"affiliations":[{"name":"Department of Computer Science","address":null}],"nessieId":"111669800541"},{"fullName":"Tao Huang","firstName":null,"middleName":null,"lastName":null,"image":{"height":null,"url":"https://loop.frontiersin.org/images/profile/552766/70","width":null,"caption":null},"loopProfileUrl":"https://loop.frontiersin.org/people/552766/overview","affiliation":{"name":"Bio-Med Big Data Center","address":null},"affiliations":[{"name":"Bio-Med Big Data Center","address":null},{"name":"CAS Key Laboratory of Tissue Microenvironment and Tumor","address":null}],"nessieId":"85899992355"},{"fullName":"Yu-Dong Cai","firstName":null,"middleName":null,"lastName":null,"image":{"height":null,"url":"https://loop.frontiersin.org/images/profile/103860/70","width":null,"caption":null},"loopProfileUrl":"https://loop.frontiersin.org/people/103860/overview","affiliation":{"name":"School of Life Sciences","address":null},"affiliations":[{"name":"School of Life Sciences","address":null}],"nessieId":"34360386087"}],"dates":{"acceptedDate":"2022-06-21","recentDate":"2022-07-19"},"doi":"10.3389/fmolb.2022.952626","frontiersExtra":{"articleType":"Original Research","impact":{"citations":19,"crossrefCitations":0,"downloads":113,"frontiersViews":0,"pmcDownloads":0,"pmcViews":0,"scopusCitations":0,"views":3457},"isPartOfResearchTopic":true,"isPublished":true,"section":"Molecular Diagnostics and Therapeutics"},"guid":952626,"images":[{"height":269,"url":"https://www.frontiersin.org/files/myhome article library/952626/952626_Thumb_400.jpg","width":400,"caption":null},{"height":410,"url":"https://www.frontiersin.org/files/Articles/952626/fmolb-09-952626-HTML/image_m/fmolb-09-952626-g001.jpg","width":1052,"caption":null},{"height":705,"url":"https://www.frontiersin.org/files/Articles/952626/fmolb-09-952626-HTML/image_m/fmolb-09-952626-g002.jpg","width":1052,"caption":null},{"height":692,"url":"https://www.frontiersin.org/files/Articles/952626/fmolb-09-952626-HTML/image_m/fmolb-09-952626-g003.jpg","width":1038,"caption":null},{"height":266,"url":"https://www.frontiersin.org/files/Articles/952626/fmolb-09-952626-HTML/image_m/fmolb-09-952626-g004.jpg","width":505,"caption":null},{"height":270,"url":"https://www.frontiersin.org/files/Articles/952626/fmolb-09-952626-HTML/image_m/fmolb-09-952626-g005.jpg","width":505,"caption":null},{"height":1091,"url":"https://www.frontiersin.org/files/Articles/952626/fmolb-09-952626-HTML/image_m/fmolb-09-952626-g006.jpg","width":1072,"caption":null}],"journal":{"guid":698,"name":"Frontiers in Molecular Biosciences","link":null,"nessieId":null,"palette":null,"publisher":"Frontiers Media","images":null,"isOnline":null,"isDeleted":null,"isDisabled":null,"issn":null},"link":"https://www.frontiersin.org/articles/10.3389/fmolb.2022.952626","pubDate":"2022-07-19","score":33.23159205802611,"title":"Identification of COVID-19-Specific Immune Markers Using a Machine Learning Method","topics":["machine learning","Feature Selection","immune cell","Classification algorithm","COVID-19"],"pdfUrl":"https://www.frontiersin.org/articles/10.3389/fmolb.2022.952626/pdf"},{"__typename":"Feed_Article","_id":"680951a40631c3389bc5249c","abstract":"The occurrence of coronavirus disease 2019 (COVID-19) has become a serious challenge to global public health. Definitive and effective treatments for COVID-19 are still lacking, and targeted antiviral drugs are not available. In addition, viruses can regulate host innate immunity and antiviral processes through the epigenome to promote viral self-replication and disease progression. In this study, we first analyzed the methylation dataset of COVID-19 using the Monte Carlo feature selection method to obtain a feature list. This feature list was subjected to the incremental feature selection method combined with a decision tree algorithm to extract key biomarkers, build effective classification models and classification rules that can remarkably distinguish patients with or without COVID-19. EPSTI1, NACAP1, SHROOM3, C19ORF35, and MX1 as the essential features play important roles in the infection and immune response to novel coronavirus. The six significant rules extracted from the optimal classifier quantitatively explained the expression pattern of COVID-19. Therefore, these findings validated that our method can distinguish COVID-19 at the methylation level and provide guidance for the diagnosis and treatment of COVID-19.","htmlAbstract":"\u003cp\u003eThe occurrence of coronavirus disease 2019 (COVID-19) has become a serious challenge to global public health. Definitive and effective treatments for COVID-19 are still lacking, and targeted antiviral drugs are not available. In addition, viruses can regulate host innate immunity and antiviral processes through the epigenome to promote viral self-replication and disease progression. In this study, we first analyzed the methylation dataset of COVID-19 using the Monte Carlo feature selection method to obtain a feature list. This feature list was subjected to the incremental feature selection method combined with a decision tree algorithm to extract key biomarkers, build effective classification models and classification rules that can remarkably distinguish patients with or without COVID-19. EPSTI1, NACAP1, SHROOM3, C19ORF35, and MX1 as the essential features play important roles in the infection and immune response to novel coronavirus. The six significant rules extracted from the optimal classifier quantitatively explained the expression pattern of COVID-19. Therefore, these findings validated that our method can distinguish COVID-19 at the methylation level and provide guidance for the diagnosis and treatment of COVID-19.\u003c/p\u003e","authors":[{"fullName":"Zhandong Li","firstName":null,"middleName":null,"lastName":null,"image":{"height":null,"url":"https://loop.frontiersin.org/images/profile/928572/70","width":null,"caption":null},"loopProfileUrl":"https://loop.frontiersin.org/people/928572/overview","affiliation":{"name":"College of Biological and Food Engineering","address":null},"affiliations":[{"name":"College of Biological and Food Engineering","address":null}],"nessieId":"8590583466"},{"fullName":"Zi Mei","firstName":null,"middleName":null,"lastName":null,"image":{"height":null,"url":"https://loop.frontiersin.org/images/profile/1795026/70","width":null,"caption":null},"loopProfileUrl":"https://loop.frontiersin.org/people/1795026/overview","affiliation":{"name":"Shanghai Institute of Nutrition and Health","address":null},"affiliations":[{"name":"Shanghai Institute of Nutrition and Health","address":null}],"nessieId":"77310071221"},{"fullName":"Shijian Ding","firstName":null,"middleName":null,"lastName":null,"image":{"height":null,"url":"https://loop.frontiersin.org/images/profile/1210689/70","width":null,"caption":null},"loopProfileUrl":"https://loop.frontiersin.org/people/1210689/overview","affiliation":{"name":"School of Life Sciences","address":null},"affiliations":[{"name":"School of Life Sciences","address":null}],"nessieId":"266288507926"},{"fullName":"Lei Chen","firstName":null,"middleName":null,"lastName":null,"image":{"height":null,"url":"https://loop.frontiersin.org/images/profile/576896/70","width":null,"caption":null},"loopProfileUrl":"https://loop.frontiersin.org/people/576896/overview","affiliation":{"name":"College of Information Engineering","address":null},"affiliations":[{"name":"College of Information Engineering","address":null}],"nessieId":null},{"fullName":"Hao Li","firstName":null,"middleName":null,"lastName":null,"image":{"height":null,"url":"https://loop.frontiersin.org/images/profile/947781/70","width":null,"caption":null},"loopProfileUrl":"https://loop.frontiersin.org/people/947781/overview","affiliation":{"name":"College of Biological and Food Engineering","address":null},"affiliations":[{"name":"College of Biological and Food Engineering","address":null}],"nessieId":"146029536994"},{"fullName":"Kaiyan Feng","firstName":null,"middleName":null,"lastName":null,"image":{"height":null,"url":"https://loop.frontiersin.org/images/profile/777635/70","width":null,"caption":null},"loopProfileUrl":"https://loop.frontiersin.org/people/777635/overview","affiliation":{"name":"Department of Computer Science","address":null},"affiliations":[{"name":"Department of Computer Science","address":null}],"nessieId":"111669800541"},{"fullName":"Tao Huang","firstName":null,"middleName":null,"lastName":null,"image":{"height":null,"url":"https://loop.frontiersin.org/images/profile/552766/70","width":null,"caption":null},"loopProfileUrl":"https://loop.frontiersin.org/people/552766/overview","affiliation":{"name":"Bio-Med Big Data Center","address":null},"affiliations":[{"name":"Bio-Med Big Data Center","address":null},{"name":"CAS Key Laboratory of Tissue Microenvironment and Tumor","address":null}],"nessieId":"85899992355"},{"fullName":"Yu-Dong Cai","firstName":null,"middleName":null,"lastName":null,"image":{"height":null,"url":"https://loop.frontiersin.org/images/profile/103860/70","width":null,"caption":null},"loopProfileUrl":"https://loop.frontiersin.org/people/103860/overview","affiliation":{"name":"School of Life Sciences","address":null},"affiliations":[{"name":"School of Life Sciences","address":null}],"nessieId":"34360386087"}],"dates":{"acceptedDate":"2022-04-27","recentDate":"2022-05-10"},"doi":"10.3389/fmolb.2022.908080","frontiersExtra":{"articleType":"Original Research","impact":{"citations":9,"crossrefCitations":0,"downloads":68,"frontiersViews":0,"pmcDownloads":0,"pmcViews":0,"scopusCitations":0,"views":2143},"isPartOfResearchTopic":true,"isPublished":true,"section":"Molecular Diagnostics and Therapeutics"},"guid":908080,"images":[{"height":215,"url":"https://www.frontiersin.org/files/myhome article library/908080/908080_Thumb_400.jpg","width":400,"caption":null},{"height":516,"url":"https://www.frontiersin.org/files/Articles/908080/fmolb-09-908080-HTML/image_m/fmolb-09-908080-g001.jpg","width":782,"caption":"Flowchart of the computational method in this study. A systematic analysis process that integrates feature selection, DT algorithms, and rule learning was applied to identify COVID-19 methylation site features. The optimal classifier, methylation sites, and rules were determined based on the performance of the DT model and the importance of the features in each model."},{"height":279,"url":"https://www.frontiersin.org/files/Articles/908080/fmolb-09-908080-HTML/image_m/fmolb-09-908080-g002.jpg","width":512,"caption":"IFS curves obtained by DT classification models on the top 1000 features of the COVID-19 dataset. The model produced the highest F1-measure of 0.990 when the top 50 features were used."},{"height":274,"url":"https://www.frontiersin.org/files/Articles/908080/fmolb-09-908080-HTML/image_m/fmolb-09-908080-g003.jpg","width":512,"caption":"Performance of the best DT model and DT model with informative features. The best DT model is superior to the DT model with informative features."}],"journal":{"guid":698,"name":"Frontiers in Molecular Biosciences","link":null,"nessieId":null,"palette":null,"publisher":"Frontiers Media","images":null,"isOnline":null,"isDeleted":null,"isDisabled":null,"issn":null},"link":"https://www.frontiersin.org/articles/10.3389/fmolb.2022.908080","pubDate":"2022-05-10","score":17.833687449629934,"title":"Identifying Methylation Signatures and Rules for COVID-19 With Machine Learning Methods","topics":["Methylation","Feature Selection","decision tree","Rule","COVID-19"],"pdfUrl":"https://www.frontiersin.org/articles/10.3389/fmolb.2022.908080/pdf"},{"__typename":"Feed_Article","_id":"680951a40631c3389bc5249d","abstract":"Gastric cancer (GC) is one of the most common malignant tumors and ranks third in cancer mortality globally. Although, a lot of advancements have been made in diagnosis and treatment of gastric cancer, there is still lack of ideal biomarker for the diagnosis and treatment of gastric cancer. Due to the poor prognosis, the survival rate is not improved much. Circular RNAs (circRNAs) are single-stranded RNAs with a covalently closed loop structure that don’t have the 5′-3′ polarity and a 3′ polyA tail. Because of their circular structure, circRNAs are more stable than linear RNAs. Previous studies have found that circRNAs are involved in several biological processes like cell cycle, proliferation, apoptosis, autophagy, migration and invasion in different cancers, and participate in some molecular mechanisms including sponging microRNAs (miRNAs), protein translation and binding to RNA-binding proteins. Several studies have reported that circRNAs play crucial role in the occurrence and development of different types of cancers. Although, some studies have reported several circRNAs in gastric cancer, more studies are needed in searching new biomarkers for gastric cancer diagnosis and treatment. Here, we investigated potential circRNA biomarkers for GC using next-generation sequencing (NGS) data collected from 5 paired GC samples. A total of 45,783 circRNAs were identified in all samples and among them 478 were differentially expressed (DE). The gene ontology (GO) analysis of the host genes of the DE circRNAs showed that some genes were enriched in several important biological processes, molecular functions and cellular components. The Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis revealed that some host genes were enriched in several GC related pathways. The circRNA-miRNA-gene interaction network analysis showed that two circRNAs circCEACAM5 and circCOL1A1 were interacted with gastric cancer related miRNAs, and their host genes were also the important therapeutic and prognostic biomarkers for GC. The experimental results also validated that these two circRNAs were DE in GC compared to adjacent normal tissues. Overall, our findings suggest that these two circRNAs circCEACAM5 and circCOL1A1 might be the potential biomarkers for the diagnosis and treatment of GC.","htmlAbstract":"\u003cp\u003eGastric cancer (GC) is one of the most common malignant tumors and ranks third in cancer mortality globally. Although, a lot of advancements have been made in diagnosis and treatment of gastric cancer, there is still lack of ideal biomarker for the diagnosis and treatment of gastric cancer. Due to the poor prognosis, the survival rate is not improved much. Circular RNAs (circRNAs) are single-stranded RNAs with a covalently closed loop structure that don\u0026#x2019;t have the 5\u0026#x2032;-3\u0026#x2032; polarity and a 3\u0026#x2032; polyA tail. Because of their circular structure, circRNAs are more stable than linear RNAs. Previous studies have found that circRNAs are involved in several biological processes like cell cycle, proliferation, apoptosis, autophagy, migration and invasion in different cancers, and participate in some molecular mechanisms including sponging microRNAs (miRNAs), protein translation and binding to RNA-binding proteins. Several studies have reported that circRNAs play crucial role in the occurrence and development of different types of cancers. Although, some studies have reported several circRNAs in gastric cancer, more studies are needed in searching new biomarkers for gastric cancer diagnosis and treatment. Here, we investigated potential circRNA biomarkers for GC using next-generation sequencing (NGS) data collected from 5 paired GC samples. A total of 45,783 circRNAs were identified in all samples and among them 478 were differentially expressed (DE). The gene ontology (GO) analysis of the host genes of the DE circRNAs showed that some genes were enriched in several important biological processes, molecular functions and cellular components. The Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis revealed that some host genes were enriched in several GC related pathways. The circRNA-miRNA-gene interaction network analysis showed that two circRNAs circCEACAM5 and circCOL1A1 were interacted with gastric cancer related miRNAs, and their host genes were also the important therapeutic and prognostic biomarkers for GC. The experimental results also validated that these two circRNAs were DE in GC compared to adjacent normal tissues. Overall, our findings suggest that these two circRNAs circCEACAM5 and circCOL1A1 might be the potential biomarkers for the diagnosis and treatment of GC.\u003c/p\u003e","authors":[{"fullName":"Md. Tofazzal Hossain","firstName":null,"middleName":null,"lastName":null,"image":{"height":null,"url":"https://loop.frontiersin.org/images/profile/1601096/70","width":null,"caption":null},"loopProfileUrl":"https://loop.frontiersin.org/people/1601096/overview","affiliation":{"name":"University of Chinese Academy of Sciences","address":null},"affiliations":[{"name":"University of Chinese Academy of Sciences","address":null},{"name":"Center for High Performance Computing","address":null},{"name":"Department of Statistics","address":null}],"nessieId":null},{"fullName":"Song Li","firstName":null,"middleName":null,"lastName":null,"image":null,"loopProfileUrl":null,"affiliation":{"name":"Shenzhen Science \u0026 Technology Development Exchange Center","address":null},"affiliations":[{"name":"Shenzhen Science \u0026 Technology Development Exchange Center","address":null}],"nessieId":null},{"fullName":"Md. 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