This study aims to discover the genetic modules that distinguish glioblastoma multiforme (GBM) from low-grade glioma (LGG) and identify hub genes. A co-expression network is constructed using the expression profiles of 28 GBM and LGG patients from the Gene Expression Omnibus database. The authors performed gene ontology (GO) and Kyoto encyclopaedia of genes and genomes (KEGG) analysis on these genes. The maximal clique centrality method was used to identify hub genes. Online tools were employed to confirm the link between hub gene expression and overall patient survival rate. The top 5000 genes with major variance were classified into 18 co-expression gene modules. GO analysis indicated that abnormal changes in ‘cell migration’ and ‘collagen metabolic process’ were involved in the development of GBM. KEGG analysis suggested that ‘focal adhesion’ and ‘p53 signalling pathway’ regulate the tumour progression. TNFAIP6 was identified as a hub gene, and the expression of TNFAIP6 was increased with the elevation of pathological grade. Survival analysis indicated that the higher the expression of TNFAIP6, the shorter the survival time of patients. The authors identified TNFAIP6 as the hub gene in the progression of GBM, and its high expression indicates the poor prognosis of the patients.
{"title":"Identification of TNFAIP6 as a hub gene associated with the progression of glioblastoma by weighted gene co-expression network analysis","authors":"Dongdong Lin, Wei Li, Nu Zhang, Ming Cai","doi":"10.1049/syb2.12046","DOIUrl":"10.1049/syb2.12046","url":null,"abstract":"<p>This study aims to discover the genetic modules that distinguish glioblastoma multiforme (GBM) from low-grade glioma (LGG) and identify hub genes. A co-expression network is constructed using the expression profiles of 28 GBM and LGG patients from the Gene Expression Omnibus database. The authors performed gene ontology (GO) and Kyoto encyclopaedia of genes and genomes (KEGG) analysis on these genes. The maximal clique centrality method was used to identify hub genes. Online tools were employed to confirm the link between hub gene expression and overall patient survival rate. The top 5000 genes with major variance were classified into 18 co-expression gene modules. GO analysis indicated that abnormal changes in ‘cell migration’ and ‘collagen metabolic process’ were involved in the development of GBM. KEGG analysis suggested that ‘focal adhesion’ and ‘p53 signalling pathway’ regulate the tumour progression. TNFAIP6 was identified as a hub gene, and the expression of TNFAIP6 was increased with the elevation of pathological grade. Survival analysis indicated that the higher the expression of TNFAIP6, the shorter the survival time of patients. The authors identified TNFAIP6 as the hub gene in the progression of GBM, and its high expression indicates the poor prognosis of the patients.</p>","PeriodicalId":50379,"journal":{"name":"IET Systems Biology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2022-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9469790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40404350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acute paraquat poisoning is due to the extremely severe toxicity of paraquat. After paraquat enters the human body, it will cause rapid changes in the human body system. Since paraquat poisoning will quickly invade the organs of the whole body, it may cause damage to the functions of multiple organs in the poisoned patient. The liver organ is the most important detoxification site for the human body, so the damage to the liver of the patient is more obvious. This article discovers and observes the structure of paraquat and the dynamic changes of serum cytokines in patients with paraquat poisoning through the clinical phenomenon of paraquat poisoning, and the related changes of human serum cells after the subjects took paraquat and the changes of cell dynamic factors after different doses of paraquat entered the human body were analysed. At the same time, the changes in the immune function of the body of different groups of people were also observed. The experimental results in this article show that according to the intake of paraquat, the severity of poisoning patients will be mild, moderate, severe and outbreak poisoning. Among them, the dose for adults who cannot be treated for prognosis is 10 ml.
{"title":"Dynamic changes of serum cytokines in acute paraquat poisoning and changes in patients' immune function","authors":"Huimin Yuan, Qian Liu, Yulan Yu","doi":"10.1049/syb2.12045","DOIUrl":"10.1049/syb2.12045","url":null,"abstract":"<p>Acute paraquat poisoning is due to the extremely severe toxicity of paraquat. After paraquat enters the human body, it will cause rapid changes in the human body system. Since paraquat poisoning will quickly invade the organs of the whole body, it may cause damage to the functions of multiple organs in the poisoned patient. The liver organ is the most important detoxification site for the human body, so the damage to the liver of the patient is more obvious. This article discovers and observes the structure of paraquat and the dynamic changes of serum cytokines in patients with paraquat poisoning through the clinical phenomenon of paraquat poisoning, and the related changes of human serum cells after the subjects took paraquat and the changes of cell dynamic factors after different doses of paraquat entered the human body were analysed. At the same time, the changes in the immune function of the body of different groups of people were also observed. The experimental results in this article show that according to the intake of paraquat, the severity of poisoning patients will be mild, moderate, severe and outbreak poisoning. Among them, the dose for adults who cannot be treated for prognosis is 10 ml.</p>","PeriodicalId":50379,"journal":{"name":"IET Systems Biology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2022-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/92/4b/SYB2-16-132.PMC9290778.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40401313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Song Xie, Jiajun Yang, Shenghui Huang, Yuanlan Fan, Tao Xu, Jiangshuang He, Jiahao Guo, Xiang Ji, Zhibo Wang, Peijun Li, Jiangfan Chen, Yi Zhang
The cingulate cortex is part of the conserved limbic system, which is considered as a hub of emotional and cognitive control. Accumulating evidence suggested that involvement of the cingulate cortex is significant for cognitive impairment of Parkinson's disease (PD). However, mechanistic studies of the cingulate cortex in PD pathogenesis are limited. Here, transcriptomic and regulatory network analyses were conducted for the cingulate cortex in PD. Enrichment and clustering analyses showed that genes involved in regulation of membrane potential and glutamate receptor signalling pathway were upregulated. Importantly, myelin genes and the oligodendrocyte development pathways were markedly downregulated, indicating disrupted myelination in PD cingulate cortex. Cell-type-specific signatures revealed that myelinating oligodendrocytes were the major cell type damaged in the PD cingulate cortex. Furthermore, downregulation of myelination pathways in the cingulate cortex were shared and validated in another independent RNAseq cohort of dementia with Lewy bodies (DLB). In combination with ATACseq data, gene regulatory networks (GRNs) were further constructed for 32 transcription factors (TFs) and 466 target genes among differentially expressed genes (DEGs) using a tree-based machine learning algorithm. Several transcription factors, including Olig2, Sox8, Sox10, E2F1, and NKX6-2, were highlighted as key nodes in a sub-network, which control many overlapping downstream targets associated with myelin formation and gliogenesis. In addition, the authors have validated a subset of DEGs by qPCRs in two PD mouse models. Notably, seven of these genes,TOX3, NECAB2 NOS1, CAPN3, NR4A2, E2F1 and FOXP2, have been implicated previously in PD or neurodegeneration and are worthy of further studies as novel candidate genes. Together, our findings provide new insights into the role of remyelination as a promising new approach to treat PD after demyelination.
{"title":"Disrupted myelination network in the cingulate cortex of Parkinson's disease","authors":"Song Xie, Jiajun Yang, Shenghui Huang, Yuanlan Fan, Tao Xu, Jiangshuang He, Jiahao Guo, Xiang Ji, Zhibo Wang, Peijun Li, Jiangfan Chen, Yi Zhang","doi":"10.1049/syb2.12043","DOIUrl":"10.1049/syb2.12043","url":null,"abstract":"<p>The cingulate cortex is part of the conserved limbic system, which is considered as a hub of emotional and cognitive control. Accumulating evidence suggested that involvement of the cingulate cortex is significant for cognitive impairment of Parkinson's disease (PD). However, mechanistic studies of the cingulate cortex in PD pathogenesis are limited. Here, transcriptomic and regulatory network analyses were conducted for the cingulate cortex in PD. Enrichment and clustering analyses showed that genes involved in regulation of membrane potential and glutamate receptor signalling pathway were upregulated. Importantly, myelin genes and the oligodendrocyte development pathways were markedly downregulated, indicating disrupted myelination in PD cingulate cortex. Cell-type-specific signatures revealed that myelinating oligodendrocytes were the major cell type damaged in the PD cingulate cortex. Furthermore, downregulation of myelination pathways in the cingulate cortex were shared and validated in another independent RNAseq cohort of dementia with Lewy bodies (DLB). In combination with ATACseq data, gene regulatory networks (GRNs) were further constructed for 32 transcription factors (TFs) and 466 target genes among differentially expressed genes (DEGs) using a tree-based machine learning algorithm. Several transcription factors, including Olig2, Sox8, Sox10, E2F1, and NKX6-2, were highlighted as key nodes in a sub-network, which control many overlapping downstream targets associated with myelin formation and gliogenesis. In addition, the authors have validated a subset of DEGs by qPCRs in two PD mouse models. Notably, seven of these genes,TOX3, NECAB2 NOS1, CAPN3, NR4A2, E2F1 and FOXP2, have been implicated previously in PD or neurodegeneration and are worthy of further studies as novel candidate genes. Together, our findings provide new insights into the role of remyelination as a promising new approach to treat PD after demyelination.</p>","PeriodicalId":50379,"journal":{"name":"IET Systems Biology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2022-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ietresearch.onlinelibrary.wiley.com/doi/epdf/10.1049/syb2.12043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46356053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiangbin Liu, Lijun Fu, Jerry Chun-Wei Lin, Shuai Liu
Prenatal karyotype diagnosis is important to determine if the foetus has genetic diseases and some congenital diseases. Chromosome classification is an important part of karyotype analysis, and the task is tedious and lengthy. Chromosome classification methods based on deep learning have achieved good results, but if the quality of the chromosome image is not high, these methods cannot learn image features well, resulting in unsatisfactory classification results. Moreover, the existing methods generally have a poor effect on sex chromosome classification. Therefore, in this work, the authors propose to use a super-resolution network, Self-Attention Negative Feedback Network, and combine it with traditional neural networks to obtain an efficient chromosome classification method called SRAS-net. The method first inputs the low-resolution chromosome images into the super-resolution network to generate high-resolution chromosome images and then uses the traditional deep learning model to classify the chromosomes. To solve the problem of inaccurate sex chromosome classification, the authors also propose to use the SMOTE algorithm to generate a small number of sex chromosome samples to ensure a balanced number of samples while allowing the model to learn more sex chromosome features. Experimental results show that our method achieves 97.55% accuracy and is better than state-of-the-art methods.
{"title":"SRAS-net: Low-resolution chromosome image classification based on deep learning","authors":"Xiangbin Liu, Lijun Fu, Jerry Chun-Wei Lin, Shuai Liu","doi":"10.1049/syb2.12042","DOIUrl":"10.1049/syb2.12042","url":null,"abstract":"<p>Prenatal karyotype diagnosis is important to determine if the foetus has genetic diseases and some congenital diseases. Chromosome classification is an important part of karyotype analysis, and the task is tedious and lengthy. Chromosome classification methods based on deep learning have achieved good results, but if the quality of the chromosome image is not high, these methods cannot learn image features well, resulting in unsatisfactory classification results. Moreover, the existing methods generally have a poor effect on sex chromosome classification. Therefore, in this work, the authors propose to use a super-resolution network, Self-Attention Negative Feedback Network, and combine it with traditional neural networks to obtain an efficient chromosome classification method called SRAS-net. The method first inputs the low-resolution chromosome images into the super-resolution network to generate high-resolution chromosome images and then uses the traditional deep learning model to classify the chromosomes. To solve the problem of inaccurate sex chromosome classification, the authors also propose to use the SMOTE algorithm to generate a small number of sex chromosome samples to ensure a balanced number of samples while allowing the model to learn more sex chromosome features. Experimental results show that our method achieves 97.55% accuracy and is better than state-of-the-art methods.</p>","PeriodicalId":50379,"journal":{"name":"IET Systems Biology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2022-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9290780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9178707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Colon cancer (CC) is one of the most commonly diagnosed tumours worldwide. Single-cell RNA sequencing (scRNA-seq) can accurately reflect the heterogeneity within and between tumour cells and identify important genes associated with cancer development and growth. In this study, scRNA-seq was used to identify reliable prognostic biomarkers in CC. ScRNA-seq data of CC before and after 5-fluorouracil treatment were first downloaded from the Gene Expression Omnibus database. The data were pre-processed, and dimensionality reduction was performed using principal component analysis and t-distributed stochastic neighbour embedding algorithms. Additionally, the transcriptome data, somatic variant data, and clinical reports of patients with CC were obtained from The Cancer Genome Atlas database. Seven key genes were identified using Cox regression analysis and the least absolute shrinkage and selection operator method to establish signatures associated with CC prognoses. The identified signatures were validated on independent datasets, and somatic mutations and potential oncogenic pathways were further explored. Based on these features, gene signatures, and other clinical variables, a more effective predictive model nomogram for patients with CC was constructed, and a decision curve analysis was performed to assess the utility of the nomogram. A prognostic signature consisting of seven prognostic-related genes, including CAV2, EREG, NGFRAP1, WBSCR22, SPINT2, CCDC28A, and BCL10, was constructed and validated. The proficiency and credibility of the signature were verified in both internal and external datasets, and the results showed that the seven-gene signature could effectively predict the prognosis of patients with CC under various clinical conditions. A nomogram was then constructed based on features such as the RiskScore, patients' age, neoplasm stage, and tumor (T), nodes (N), and metastases (M) classification, and the nomogram had good clinical utility. Higher RiskScores were associated with a higher tumour mutational burden, which was confirmed to be a prognostic risk factor. Gene set enrichment analysis showed that high-score groups were enriched in ‘cytoplasmic DNA sensing’, ‘Extracellular matrix receptor interactions’, and ‘focal adhesion’, and low-score groups were enriched in ‘natural killer cell-mediated cytotoxicity’, and ‘T-cell receptor signalling pathways’, among other pathways. A robust seven-gene marker for CC was identified based on scRNA-seq data and was validated in multiple independent cohort studies. These findings provide a new potential marker to predict the prognosis of patients with CC.
结肠癌(CC)是世界上最常见的肿瘤之一。单细胞RNA测序(scRNA-seq)能够准确反映肿瘤细胞内及细胞间的异质性,识别与肿瘤发生生长相关的重要基因。在本研究中,scRNA-seq用于鉴定可靠的CC预后生物标志物,首先从基因表达Omnibus数据库下载5-氟尿嘧啶治疗前后CC的scRNA-seq数据。对数据进行预处理,利用主成分分析和t分布随机邻居嵌入算法进行降维。此外,从the Cancer Genome Atlas数据库中获得了CC患者的转录组数据、体细胞变异数据和临床报告。使用Cox回归分析和最小绝对收缩和选择算子方法确定了七个关键基因,以建立与CC预后相关的特征。鉴定的特征在独立的数据集上得到验证,并进一步探索体细胞突变和潜在的致癌途径。基于这些特征、基因特征和其他临床变量,构建了一个更有效的CC患者预测模型nomogram,并进行决策曲线分析来评估nomogram的效用。构建并验证了由CAV2、EREG、NGFRAP1、WBSCR22、SPINT2、CCDC28A和BCL10等7个预后相关基因组成的预后特征。在内部和外部数据集中验证了签名的熟练度和可信度,结果表明,七基因签名可以有效预测CC患者在各种临床条件下的预后。然后根据RiskScore、患者年龄、肿瘤分期、肿瘤(T)、淋巴结(N)和转移(M)分类等特征构建nomogram, nomogram具有良好的临床应用价值。较高的风险评分与较高的肿瘤突变负担相关,这被证实是一个预后风险因素。基因集富集分析显示,高分组富集于“细胞质DNA传感”、“细胞外基质受体相互作用”和“局灶黏附”,而低分组富集于“自然杀伤细胞介导的细胞毒性”和“t细胞受体信号通路”等途径。基于scRNA-seq数据确定了一个强大的七基因CC标记,并在多个独立队列研究中得到验证。这些发现为预测CC患者预后提供了一个新的潜在指标。
{"title":"Identification and validation of a seven-gene prognostic marker in colon cancer based on single-cell transcriptome analysis","authors":"Yang Zhou, Yang Guo, Yuanhe Wang","doi":"10.1049/syb2.12041","DOIUrl":"10.1049/syb2.12041","url":null,"abstract":"<p>Colon cancer (CC) is one of the most commonly diagnosed tumours worldwide. Single-cell RNA sequencing (scRNA-seq) can accurately reflect the heterogeneity within and between tumour cells and identify important genes associated with cancer development and growth. In this study, scRNA-seq was used to identify reliable prognostic biomarkers in CC. ScRNA-seq data of CC before and after 5-fluorouracil treatment were first downloaded from the Gene Expression Omnibus database. The data were pre-processed, and dimensionality reduction was performed using principal component analysis and t-distributed stochastic neighbour embedding algorithms. Additionally, the transcriptome data, somatic variant data, and clinical reports of patients with CC were obtained from The Cancer Genome Atlas database. Seven key genes were identified using Cox regression analysis and the least absolute shrinkage and selection operator method to establish signatures associated with CC prognoses. The identified signatures were validated on independent datasets, and somatic mutations and potential oncogenic pathways were further explored. Based on these features, gene signatures, and other clinical variables, a more effective predictive model nomogram for patients with CC was constructed, and a decision curve analysis was performed to assess the utility of the nomogram. A prognostic signature consisting of seven prognostic-related genes, including <i>CAV2</i>, <i>EREG</i>, <i>NGFRAP1</i>, <i>WBSCR22</i>, <i>SPINT2</i>, <i>CCDC28A</i>, and <i>BCL10</i>, was constructed and validated. The proficiency and credibility of the signature were verified in both internal and external datasets, and the results showed that the seven-gene signature could effectively predict the prognosis of patients with CC under various clinical conditions. A nomogram was then constructed based on features such as the RiskScore, patients' age, neoplasm stage, and tumor (T), nodes (N), and metastases (M) classification, and the nomogram had good clinical utility. Higher RiskScores were associated with a higher tumour mutational burden, which was confirmed to be a prognostic risk factor. Gene set enrichment analysis showed that high-score groups were enriched in ‘cytoplasmic DNA sensing’, ‘Extracellular matrix receptor interactions’, and ‘focal adhesion’, and low-score groups were enriched in ‘natural killer cell-mediated cytotoxicity’, and ‘T-cell receptor signalling pathways’, among other pathways. A robust seven-gene marker for CC was identified based on scRNA-seq data and was validated in multiple independent cohort studies. These findings provide a new potential marker to predict the prognosis of patients with CC.</p>","PeriodicalId":50379,"journal":{"name":"IET Systems Biology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2022-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ietresearch.onlinelibrary.wiley.com/doi/epdf/10.1049/syb2.12041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43690326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yandong Miao, Bin Su, Xiaolong Tang, Jiangtao Wang, Wuxia Quan, Yonggang Chen, Denghai Mi
N6-methyladenosine (m6A) RNA methylation is correlated with carcinogenesis and dynamically possessed through the m6A RNA methylation regulators. This paper aimed to explore 13 m6A RNA methylation regulators' role in gastrointestinal cancer (GIC) and determine the risk model and prognosis value of m6A RNA methylation regulators in GIC. We used several bioinformatics methods to identify the differential expression of m6A RNA methylation regulators in GIC, constructed a prognostic model, and carried out functional enrichment analysis. Eleven of 13 m6A RNA methylation regulators were differentially expressed in different clinicopathological characteristics of GIC, and m6A RNA methylation regulators were nearly associated with GIC. We constructed a risk model based on five m6A RNA methylation regulators (METTL3, FTO, YTHDF1, ZC3H13, and WTAP); the risk score is an independent prognosis biomarker. Moreover, the five m6A RNA methylation regulators can also forecast the 1-, 3- and 5-year overall survival through a nomogram. Furthermore, four hallmarks of oxidative phosphorylation, glycolysis, fatty acid metabolism, and cholesterol homoeostasis gene sets were significantly enriched in GIC. m6A RNA methylation regulators were related to the malignant clinicopathological characteristics of GIC and may be used for prognostic stratification and development of therapeutic strategies.
{"title":"Construction and validation of m6A RNA methylation regulators associated prognostic model for gastrointestinal cancer","authors":"Yandong Miao, Bin Su, Xiaolong Tang, Jiangtao Wang, Wuxia Quan, Yonggang Chen, Denghai Mi","doi":"10.1049/syb2.12040","DOIUrl":"10.1049/syb2.12040","url":null,"abstract":"<p>N6-methyladenosine (m<sup>6</sup>A) RNA methylation is correlated with carcinogenesis and dynamically possessed through the m<sup>6</sup>A RNA methylation regulators. This paper aimed to explore 13 m<sup>6</sup>A RNA methylation regulators' role in gastrointestinal cancer (GIC) and determine the risk model and prognosis value of m<sup>6</sup>A RNA methylation regulators in GIC. We used several bioinformatics methods to identify the differential expression of m<sup>6</sup>A RNA methylation regulators in GIC, constructed a prognostic model, and carried out functional enrichment analysis. Eleven of 13 m<sup>6</sup>A RNA methylation regulators were differentially expressed in different clinicopathological characteristics of GIC, and m<sup>6</sup>A RNA methylation regulators were nearly associated with GIC. We constructed a risk model based on five m<sup>6</sup>A RNA methylation regulators (METTL3, FTO, YTHDF1, ZC3H13, and WTAP); the risk score is an independent prognosis biomarker. Moreover, the five m<sup>6</sup>A RNA methylation regulators can also forecast the 1-, 3- and 5-year overall survival through a nomogram. Furthermore, four hallmarks of oxidative phosphorylation, glycolysis, fatty acid metabolism, and cholesterol homoeostasis gene sets were significantly enriched in GIC. m<sup>6</sup>A RNA methylation regulators were related to the malignant clinicopathological characteristics of GIC and may be used for prognostic stratification and development of therapeutic strategies.</p>","PeriodicalId":50379,"journal":{"name":"IET Systems Biology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2022-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/16/3b/SYB2-16-59.PMC8965361.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39930575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-02-01Epub Date: 2021-10-14DOI: 10.1049/syb2.12036
Shiyang Xie, Yaxuan Wang, Jin Huang, Guang Li
Liver hepatocellular carcinoma (LIHC) comprises most cases of liver cancer with a poor prognosis. N6 -methyladenosine (m6A) plays important biological functions in cancers. Thus, the present research was aimed to determine biomarkers of m6A regulators that could effectively predict the prognosis of LIHC patients. Based on the data collected from the Cancer Genome Atlas (TCGA) database, the correlation between the mRNA expression levels and copy number variation (CNV) patterns were determined. Higher mRNA expression resulted from the increasing number of 9 genes. Using the univariate Cox regression analysis, 11 m6A regulators that had close correlations with the LIHC prognosis were identified. In addition, under the support of the multivariate Cox regression models and the least absolute shrinkage and selection operator, a 4-gene (YTHDF2, IGF2BP3, KIAA1429, and ALKBH5) signature of m6A regulators was constructed. This signature was expected to present a prognostic value in LIHC (log-rank test p value < 0.0001). The GSE76427 (n = 94) and ICGC-LIRI-JP (n = 212) datasets were used to validate the prognostic signature, suggesting strong power to predict patients' prognosis for LIHC. To sum up, genetic alterations in m6A regulatory genes were identified as reliable and effective biomarkers for predicting the prognosis of LIHC patients.
{"title":"A novel m6A-related prognostic signature for predicting the overall survival of hepatocellular carcinoma patients.","authors":"Shiyang Xie, Yaxuan Wang, Jin Huang, Guang Li","doi":"10.1049/syb2.12036","DOIUrl":"https://doi.org/10.1049/syb2.12036","url":null,"abstract":"<p><p>Liver hepatocellular carcinoma (LIHC) comprises most cases of liver cancer with a poor prognosis. N<sup>6</sup> -methyladenosine (m6A) plays important biological functions in cancers. Thus, the present research was aimed to determine biomarkers of m6A regulators that could effectively predict the prognosis of LIHC patients. Based on the data collected from the Cancer Genome Atlas (TCGA) database, the correlation between the mRNA expression levels and copy number variation (CNV) patterns were determined. Higher mRNA expression resulted from the increasing number of 9 genes. Using the univariate Cox regression analysis, 11 m6A regulators that had close correlations with the LIHC prognosis were identified. In addition, under the support of the multivariate Cox regression models and the least absolute shrinkage and selection operator, a 4-gene (YTHDF2, IGF2BP3, KIAA1429, and ALKBH5) signature of m6A regulators was constructed. This signature was expected to present a prognostic value in LIHC (log-rank test p value < 0.0001). The GSE76427 (n = 94) and ICGC-LIRI-JP (n = 212) datasets were used to validate the prognostic signature, suggesting strong power to predict patients' prognosis for LIHC. To sum up, genetic alterations in m6A regulatory genes were identified as reliable and effective biomarkers for predicting the prognosis of LIHC patients.</p>","PeriodicalId":50379,"journal":{"name":"IET Systems Biology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8849219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39516666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Identification of drug-target interactions (DTIs) has great practical importance in the drug discovery process for known diseases. However, only a small proportion of DTIs in these databases has been verified experimentally, and the computational methods for predicting the interactions remain challenging. As a result, some effective computational models have become increasingly popular for predicting DTIs. In this work, the authors predict potential DTIs from the local structure of drug-target associations' network, which is different from the traditional global network similarity methods based on structure and ligand. A novel method called PPDTS is proposed to predict DTIs. First, according to the DTIs' network local structure, the known DTIs are converted into a binary network. Second, the Resource Allocation algorithm is used to obtain a drug-drug similarity network and a target-target similarity network. Third, a Collaborative Filtering algorithm is used with the known drug-target topology information to obtain similarity scores. Fourth, the linear combination of drug-target similarity model and the target-drug similarity model are innovatively proposed to obtain the final prediction results. Finally, the experimental performance of PPDTS has proved to be higher than that of the previously mentioned four popular network-based similarity methods, which is validated in different experimental datasets. Some of the predicted results can be supported in UniProt and DrugBank databases.
{"title":"PPDTS: Predicting potential drug-target interactions based on network similarity.","authors":"Wei Wang, Yongqing Wang, Yu Zhang, Dong Liu, Hongjun Zhang, Xianfang Wang","doi":"10.1049/syb2.12037","DOIUrl":"https://doi.org/10.1049/syb2.12037","url":null,"abstract":"<p><p>Identification of drug-target interactions (DTIs) has great practical importance in the drug discovery process for known diseases. However, only a small proportion of DTIs in these databases has been verified experimentally, and the computational methods for predicting the interactions remain challenging. As a result, some effective computational models have become increasingly popular for predicting DTIs. In this work, the authors predict potential DTIs from the local structure of drug-target associations' network, which is different from the traditional global network similarity methods based on structure and ligand. A novel method called PPDTS is proposed to predict DTIs. First, according to the DTIs' network local structure, the known DTIs are converted into a binary network. Second, the Resource Allocation algorithm is used to obtain a drug-drug similarity network and a target-target similarity network. Third, a Collaborative Filtering algorithm is used with the known drug-target topology information to obtain similarity scores. Fourth, the linear combination of drug-target similarity model and the target-drug similarity model are innovatively proposed to obtain the final prediction results. Finally, the experimental performance of PPDTS has proved to be higher than that of the previously mentioned four popular network-based similarity methods, which is validated in different experimental datasets. Some of the predicted results can be supported in UniProt and DrugBank databases.</p>","PeriodicalId":50379,"journal":{"name":"IET Systems Biology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/83/cf/SYB2-16-18.PMC8849239.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39736517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wenjun Ren, Yongwu Li, Xi Chen, Sheng Hu, Wanli Cheng, Yu Cao, Jingcheng Gao, Xia Chen, Da Xiong, Hongrong Li, Ping Wang
RYR2 mutation is clinically frequent in non-small cell lung cancer (NSCLC) with its function being elusive. We downloaded lung squamous cell carcinoma and lung adenocarcinoma samples from the TCGA database, split the samples into RYR2 mutant group (n = 337) and RYR2 wild group (n = 634), and established Kaplan-Meier curves. The results showed that RYR2 mutant group lived longer than the wild group (p = 0.027). Weighted gene co-expression network analysis (WGCNA) of differentially expressed genes (DEGs) yielded prognosis-related genes. Five mRNAs and 10 lncRNAs were selected to build survival prognostic models with other clinical features. The AUCs of 2 models are 0.622 and 0.565 for predicting survival at 3 years. Among these genes, the AUCs of DKK1 and GS1-115G20.1 expression levels were 0.607 and 0.560, respectively, which predicted the 3-year survival rate of NSCLC sufferers. GSEA identified an association of high DKK1 expression with TP53, MTOR, and VEGF expression. Several target miRNAs interacting with GS1-115G20.1 were observed to show the relationship with the phenotype, treatment, and survival of NSCLC. NSCLC patients with RYR2 mutation may obtain better prognosis by down-regulating DKK1 and up-regulating GS1-115G20.1.
{"title":"RYR2 mutation in non-small cell lung cancer prolongs survival via down-regulation of DKK1 and up-regulation of GS1-115G20.1: A weighted gene Co-expression network analysis and risk prognostic models","authors":"Wenjun Ren, Yongwu Li, Xi Chen, Sheng Hu, Wanli Cheng, Yu Cao, Jingcheng Gao, Xia Chen, Da Xiong, Hongrong Li, Ping Wang","doi":"10.1049/syb2.12038","DOIUrl":"10.1049/syb2.12038","url":null,"abstract":"<p><i>RYR2</i> mutation is clinically frequent in non-small cell lung cancer (NSCLC) with its function being elusive. We downloaded lung squamous cell carcinoma and lung adenocarcinoma samples from the TCGA database, split the samples into <i>RYR2</i> mutant group (<i>n</i> = 337) and <i>RYR2</i> wild group (<i>n</i> = 634), and established Kaplan-Meier curves. The results showed that <i>RYR2</i> mutant group lived longer than the wild group (<i>p</i> = 0.027). Weighted gene co-expression network analysis (WGCNA) of differentially expressed genes (DEGs) yielded prognosis-related genes. Five mRNAs and 10 lncRNAs were selected to build survival prognostic models with other clinical features. The AUCs of 2 models are 0.622 and 0.565 for predicting survival at 3 years. Among these genes, the AUCs of <i>DKK1</i> and <i>GS1-115G20.1</i> expression levels were 0.607 and 0.560, respectively, which predicted the 3-year survival rate of NSCLC sufferers. GSEA identified an association of high <i>DKK1</i> expression with <i>TP53</i>, <i>MTOR</i>, and <i>VEGF</i> expression. Several target miRNAs interacting with <i>GS1-115G20.1</i> were observed to show the relationship with the phenotype, treatment, and survival of NSCLC. NSCLC patients with <i>RYR2</i> mutation may obtain better prognosis by down-regulating <i>DKK1</i> and up-regulating <i>GS1-115G20.1</i>.</p>","PeriodicalId":50379,"journal":{"name":"IET Systems Biology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2021-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2f/bc/SYB2-16-43.PMC8965387.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39955582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Haipeng Xu, Yanzhi Ge, Yang Liu, Yang Zheng, Rong Hu, Conglin Ren, Qianqian Liu
Stroke is one of the leading causes of patients' death and long-term disability worldwide, and ischaemic stroke (IS) accounts for nearly 80% of all strokes. Differential genes and weighted gene co-expression network analysis (WGCNA) in male and female patients with IS were compared. The authors used cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT) to analyse the distribution pattern of immune subtypes between male and female patients. In this study, 141 up-regulated and 61 down-regulated genes were gathered and distributed into five modules in response to their correlation degree to clinical traits. The criterion for Gene Ontology (GO) term and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway indicated that detailed analysis had the potential to enhance clinical prediction and to identify the gender-related mechanism. After that, the expression levels of hub genes were measured via the quantitative real-time PCR (qRT-PCR) method. Finally, CCL20, ICAM1 and PTGS2 were identified and these may be some promising targets for sex differences in IS. Besides, the hub genes were further verified by rat experiments. Furthermore, these CIBERSORT results showed that T cells CD8 and Monocytes may be the target for the treatment of male and female patients, respectively.
{"title":"Identification of the key genes and immune infiltrating cells determined by sex differences in ischaemic stroke through co-expression network module","authors":"Haipeng Xu, Yanzhi Ge, Yang Liu, Yang Zheng, Rong Hu, Conglin Ren, Qianqian Liu","doi":"10.1049/syb2.12039","DOIUrl":"10.1049/syb2.12039","url":null,"abstract":"<p>Stroke is one of the leading causes of patients' death and long-term disability worldwide, and ischaemic stroke (IS) accounts for nearly 80% of all strokes. Differential genes and weighted gene co-expression network analysis (WGCNA) in male and female patients with IS were compared. The authors used cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT) to analyse the distribution pattern of immune subtypes between male and female patients. In this study, 141 up-regulated and 61 down-regulated genes were gathered and distributed into five modules in response to their correlation degree to clinical traits. The criterion for Gene Ontology (GO) term and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway indicated that detailed analysis had the potential to enhance clinical prediction and to identify the gender-related mechanism. After that, the expression levels of hub genes were measured via the quantitative real-time PCR (qRT-PCR) method. Finally, CCL20, ICAM1 and PTGS2 were identified and these may be some promising targets for sex differences in IS. Besides, the hub genes were further verified by rat experiments. Furthermore, these CIBERSORT results showed that T cells CD8 and Monocytes may be the target for the treatment of male and female patients, respectively.</p>","PeriodicalId":50379,"journal":{"name":"IET Systems Biology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2021-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8849259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39744883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}