Pub Date : 2024-06-07DOI: 10.1016/j.ygeno.2024.110877
Zhengchen Guo , Qi Lin , Yanan Chang , Yuanyuan An , Hua Duan
Adenomyosis (ADS) is a common gynecological disorder, and its pathogenesis remains unclear. This study explores the functions of circRNAs in the eutopic endometrium of ADS and their diagnostic efficacy for ADS. High-throughput RNA sequencing was performed on 12 eutopic endometrial samples from ADS patients and 3 control endometrial samples. Additionally, circRNAs were analyzed in conjunction with clinical features. A competitive endogenous RNA network was established based on bioinformatics analysis, comprising 3 circRNAs, 1 miRNA, and 13 mRNAs. In the ADS group, the expression levels of hsa_circ_0008959 and SLC15A4 were significantly reduced, while hsa-miR-124-3p expression was increased. SLC15A4 was associated with cell proliferation and invasion. Decreased expression of hsa_circ_0008959 and SLC15A4, along with high VAS scores and elevated hsa-miR-124-3p levels, were identified as risk factors for ADS development. The combination of hsa_circ_0008959 and VAS scores demonstrated the highest diagnostic value for ADS.
{"title":"Comprehensive analysis of circRNA-miRNA-mRNA regulatory network and novel potential biomarkers in eutopic endometrium of adenomyosis","authors":"Zhengchen Guo , Qi Lin , Yanan Chang , Yuanyuan An , Hua Duan","doi":"10.1016/j.ygeno.2024.110877","DOIUrl":"10.1016/j.ygeno.2024.110877","url":null,"abstract":"<div><p>Adenomyosis (ADS) is a common gynecological disorder, and its pathogenesis remains unclear. This study explores the functions of circRNAs in the eutopic endometrium of ADS and their diagnostic efficacy for ADS. High-throughput RNA sequencing was performed on 12 eutopic endometrial samples from ADS patients and 3 control endometrial samples. Additionally, circRNAs were analyzed in conjunction with clinical features. A competitive endogenous RNA network was established based on bioinformatics analysis, comprising 3 circRNAs, 1 miRNA, and 13 mRNAs. In the ADS group, the expression levels of hsa_circ_0008959 and SLC15A4 were significantly reduced, while hsa-miR-124-3p expression was increased. SLC15A4 was associated with cell proliferation and invasion. Decreased expression of hsa_circ_0008959 and SLC15A4, along with high VAS scores and elevated hsa-miR-124-3p levels, were identified as risk factors for ADS development. The combination of hsa_circ_0008959 and VAS scores demonstrated the highest diagnostic value for ADS.</p></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0888754324000983/pdfft?md5=e832701764e4ff63e50a13f3decc6188&pid=1-s2.0-S0888754324000983-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 : 2024-06-06DOI: 10.1016/j.ygeno.2024.110872
Mengli Cao , Lin Xiong , Xingdong Wang , Shaoke Guo , Liyan Hu , Yandong Kang , Xiaoyu Wu , Pengjia Bao , Min Chu , Chunnian Liang , Jie Pei , Xian Guo
Cattle–yak is a hybrid offspring resulting from the crossbreeding of yak and cattle, and it exhibits substantial heterosis in production performance. However, male sterility in cattle–yak remains a concern. Reports suggest that noncoding RNAs are involved in the regulation of spermatogenesis. Therefore, in this study, we comprehensively compared testicular transcription profiles among cattle, yak, and cattle–yak. Numerous differentially expressed genes (DEGs), differentially expressed circRNAs (DECs), and differentially expressed miRNAs (DEMs) were identified in the intersection of two comparison groups, namely cattle versus cattle–yak and yak versus cattle–yak, with the number of DEGs, DECs, and DEMs being 4968, 360, and 59, respectively. The DEGs in cattle–yaks, cattle, and yaks were mainly associated with spermatogenesis, male gamete generation, and sexual reproduction. Concurrently, GO and KEGG analyses indicated that DEC host genes and DEM source genes were involved in the regulation of spermatogenesis. The construction of a potential competing endogenous RNA network revealed that some differentially expressed noncoding RNAs may be involved in regulating the expression of genes related to testicular spermatogenesis, including miR-423-5p, miR-449b, miR-34b/c, and miR-15b, as well as previously unreported miR-6123 and miR-1306, along with various miRNA–circRNA interaction pairs. This study serves as a valuable reference for further investigations into the mechanisms underlying male sterility in cattle–yaks.
{"title":"Comprehensive analysis of differentially expressed mRNAs, circRNAs, and miRNAs and their ceRNA network in the testis of cattle–yak, yak, and cattle","authors":"Mengli Cao , Lin Xiong , Xingdong Wang , Shaoke Guo , Liyan Hu , Yandong Kang , Xiaoyu Wu , Pengjia Bao , Min Chu , Chunnian Liang , Jie Pei , Xian Guo","doi":"10.1016/j.ygeno.2024.110872","DOIUrl":"10.1016/j.ygeno.2024.110872","url":null,"abstract":"<div><p>Cattle–yak is a hybrid offspring resulting from the crossbreeding of yak and cattle, and it exhibits substantial heterosis in production performance. However, male sterility in cattle–yak remains a concern. Reports suggest that noncoding RNAs are involved in the regulation of spermatogenesis. Therefore, in this study, we comprehensively compared testicular transcription profiles among cattle, yak, and cattle–yak. Numerous differentially expressed genes (DEGs), differentially expressed circRNAs (DECs), and differentially expressed miRNAs (DEMs) were identified in the intersection of two comparison groups, namely cattle versus cattle–yak and yak versus cattle–yak, with the number of DEGs, DECs, and DEMs being 4968, 360, and 59, respectively. The DEGs in cattle–yaks, cattle, and yaks were mainly associated with spermatogenesis, male gamete generation, and sexual reproduction. Concurrently, GO and KEGG analyses indicated that DEC host genes and DEM source genes were involved in the regulation of spermatogenesis. The construction of a potential competing endogenous RNA network revealed that some differentially expressed noncoding RNAs may be involved in regulating the expression of genes related to testicular spermatogenesis, including miR-423-5p, miR-449b, miR-34b/c, and miR-15b, as well as previously unreported miR-6123 and miR-1306, along with various miRNA–circRNA interaction pairs. This study serves as a valuable reference for further investigations into the mechanisms underlying male sterility in cattle–yaks.</p></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0888754324000934/pdfft?md5=c76db2348bd7bb333bad9967516e5fbe&pid=1-s2.0-S0888754324000934-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141288002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 : 2024-06-06DOI: 10.1016/j.ygeno.2024.110878
Eric A. Lewallen , Da Liu , Jake Karwoski , Wilson Y. Szeto , Andre J. van Wijnen , Krzysztof Laudanski
Traumatic perioperative conditions may trigger early systemic responses, activate leukocytes and reprogram the immune system. We hypothesize that leukocyte activation may not revert to pre-surgical states, and that protracted activation may emerge with increased risks of comorbidities. We tested this concept by examining the transcriptomes of monocytes and T cells in a representative observational cohort of patients (n = 13) admitted for elective cardiac surgery. Transcriptomes in T cells and monocytes were compared from before surgery (t0), and monocytes were analyzed longitudinally after acute (t24hr), and convalescent (t3m) time points. Monocytes and T cells expressed distinct transcriptomes, reflected by statistically significant differential expression of 558 T cell related genes. Monocytes expressed genes related to protein degradation and presented atypical activation of surface markers and cytoplasmic functions over time. Additionally, monocytes exhibited limited transcriptomic heterogeneity prior to surgery, and long-term patterns of gene expression associated with atherosclerosis showed three temporally distinct signatures. These data establish that post-cardiac surgery transcriptomes of monocytes differ even at three months compared to baselines, which may reflect latent (‘smoldering’) inflammation and persistent progression of tissue degenerative processes that should inform clinical care.
创伤性围手术期情况可能会引发早期全身反应,激活白细胞并对免疫系统进行重编程。我们假设,白细胞激活可能不会恢复到手术前的状态,而长期激活可能会增加合并症的风险。我们通过研究接受择期心脏手术的代表性观察组患者(n = 13)中单核细胞和 T 细胞的转录组来验证这一观点。我们比较了手术前(t0)T 细胞和单核细胞的转录组,并在急性期(t24hr)和恢复期(t3m)的时间点后对单核细胞进行了纵向分析。单核细胞和 T 细胞表达了不同的转录组,558 个 T 细胞相关基因的表达差异具有统计学意义。单核细胞表达与蛋白质降解相关的基因,并随着时间的推移出现表面标志物和细胞质功能的非典型激活。此外,单核细胞在手术前表现出有限的转录组异质性,而与动脉粥样硬化相关的基因表达的长期模式则表现出三种不同的时间特征。这些数据表明,心脏手术后单核细胞的转录组即使在三个月后也与基线不同,这可能反映了潜伏的("燃烧的")炎症和组织变性过程的持续进展,应为临床治疗提供参考。
{"title":"Transcriptomic responses of peripheral blood leukocytes to cardiac surgery after acute inflammation, and three months recovery","authors":"Eric A. Lewallen , Da Liu , Jake Karwoski , Wilson Y. Szeto , Andre J. van Wijnen , Krzysztof Laudanski","doi":"10.1016/j.ygeno.2024.110878","DOIUrl":"10.1016/j.ygeno.2024.110878","url":null,"abstract":"<div><p>Traumatic perioperative conditions may trigger early systemic responses, activate leukocytes and reprogram the immune system. We hypothesize that leukocyte activation may not revert to pre-surgical states, and that protracted activation may emerge with increased risks of comorbidities. We tested this concept by examining the transcriptomes of monocytes and T cells in a representative observational cohort of patients (<em>n</em> = 13) admitted for elective cardiac surgery. Transcriptomes in T cells and monocytes were compared from before surgery (t<sub>0</sub>), and monocytes were analyzed longitudinally after acute (t<sub>24hr</sub>), and convalescent (t<sub>3m</sub>) time points. Monocytes and T cells expressed distinct transcriptomes, reflected by statistically significant differential expression of 558 T cell related genes. Monocytes expressed genes related to protein degradation and presented atypical activation of surface markers and cytoplasmic functions over time. Additionally, monocytes exhibited limited transcriptomic heterogeneity prior to surgery, and long-term patterns of gene expression associated with atherosclerosis showed three temporally distinct signatures. These data establish that post-cardiac surgery transcriptomes of monocytes differ even at three months compared to baselines, which may reflect latent (‘smoldering’) inflammation and persistent progression of tissue degenerative processes that should inform clinical care.</p></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0888754324000995/pdfft?md5=a5b2c12cccfc9e240403fae674871ae2&pid=1-s2.0-S0888754324000995-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 : 2024-06-06DOI: 10.1016/j.ygeno.2024.110879
Huilian Cai , Yi Zeng , Dongqiang Luo , Ying Shao , Manting Liu , Jiayu Wu , Xiaolu Gao , Jiyuan Zheng , Lisi Zhou , Feng Liu
Objective
Although programmed cell death (PCD) and diabetic nephropathy (DN) are intrinsically conneted, the interplay among various PCD forms remains elusive. In this study, We aimed at identifying independently DN-associated PCD pathways and biomarkers relevant to the related pathogenesis.
Methods
We acquired DN-related datasets from the GEO database and identified PCDs independently correlated with DN (DN-PCDs) through single-sample Gene Set Enrichment Analysis (ssGSEA) as well as, univariate and multivariate logistic regression analyses. Subsequently, applying differential expression analysis, weighted gene co-expression network analysis (WGCNA), and Mfuzz cluster analysis, we filtered the DN-PCDs pertinent to DN onset and progression. The convergence of various machine learning techniques ultimately spotlighted hub genes, substantiated through dataset meta-analyses and experimental validations, thereby confirming hub genes and related pathways expression consistencies.
Results
We harmonized four DN-related datasets (GSE1009, GSE142025, GSE30528, and GSE30529) post-batch-effect removal for subsequent analyses. Our differential expression analysis yielded 709 differentially expressed genes (DEGs), comprising 446 upregulated and 263 downregulated DEGs. Based on our ssGSEA as well as univariate and multivariate logistic regressions, apoptosis and NETotic cell death were appraised as independent risk factors for DN (Odds Ratio > 1, p < 0.05). Next, we further refined 588 apoptosis- and NETotic cell death-associated genes through WGCNA and Mfuzz analysis, resulting in the identification of 17 DN-PCDs. Integrating protein-protein interaction (PPI) network analyses, network topology, and machine learning, we pinpointed hub genes (e.g., IL33, RPL11, and CX3CR1) as significant DN risk factors with expression corroborating in subsequent meta-analyses and experimental validations. Our GSEA enrichment analysis discerned differential enrichments between DN and control samples within pathways such as IL2/STAT5, IL6/JAK/STAT3, TNF-α via NF-κB, apoptosis, and oxidative phosphorylation, with related proteins such as IL2, IL6, and TNFα, which we subsequently submitted to experimental verification.
Conclusion
Innovatively stemming from from PCD interactions, in this study, we discerned PCDs with an independent impact on DN: apoptosis and NETotic cell death. We further screened DN evolution- and progression-related biomarkers, i.e. IL33, RPL11, and CX3CR1, all of which we empirically validated. This study not only poroposes a PCD-centric perspective for DN studies but also provides evidence for PCD-mediated immune cell infiltration exploration in DN regulation. Our results could motivate further exploration of DN pathogenesis, such as how the inflammatory microenvironment mediates NETotic cell death in DN regulation, representing a promising direction for fu
{"title":"Apoptosis and NETotic cell death affect diabetic nephropathy independently: An study integrative study encompassing bioinformatics, machine learning, and experimental validation","authors":"Huilian Cai , Yi Zeng , Dongqiang Luo , Ying Shao , Manting Liu , Jiayu Wu , Xiaolu Gao , Jiyuan Zheng , Lisi Zhou , Feng Liu","doi":"10.1016/j.ygeno.2024.110879","DOIUrl":"10.1016/j.ygeno.2024.110879","url":null,"abstract":"<div><h3>Objective</h3><p>Although programmed cell death (PCD) and diabetic nephropathy (DN) are intrinsically conneted, the interplay among various PCD forms remains elusive. In this study, We aimed at identifying independently DN-associated PCD pathways and biomarkers relevant to the related pathogenesis.</p></div><div><h3>Methods</h3><p>We acquired DN-related datasets from the GEO database and identified PCDs independently correlated with DN (DN-PCDs) through single-sample Gene Set Enrichment Analysis (ssGSEA) as well as, univariate and multivariate logistic regression analyses. Subsequently, applying differential expression analysis, weighted gene co-expression network analysis (WGCNA), and Mfuzz cluster analysis, we filtered the DN-PCDs pertinent to DN onset and progression. The convergence of various machine learning techniques ultimately spotlighted hub genes, substantiated through dataset meta-analyses and experimental validations, thereby confirming hub genes and related pathways expression consistencies.</p></div><div><h3>Results</h3><p>We harmonized four DN-related datasets (GSE1009, GSE142025, GSE30528, and GSE30529) post-batch-effect removal for subsequent analyses. Our differential expression analysis yielded 709 differentially expressed genes (DEGs), comprising 446 upregulated and 263 downregulated DEGs. Based on our ssGSEA as well as univariate and multivariate logistic regressions, apoptosis and NETotic cell death were appraised as independent risk factors for DN (Odds Ratio > 1, <em>p</em> < 0.05). Next, we further refined 588 apoptosis- and NETotic cell death-associated genes through WGCNA and Mfuzz analysis, resulting in the identification of 17 DN-PCDs. Integrating protein-protein interaction (PPI) network analyses, network topology, and machine learning, we pinpointed hub genes (e.g., IL33, RPL11, and CX3CR1) as significant DN risk factors with expression corroborating in subsequent meta-analyses and experimental validations. Our GSEA enrichment analysis discerned differential enrichments between DN and control samples within pathways such as IL2/STAT5, IL6/JAK/STAT3, TNF-α via NF-κB, apoptosis, and oxidative phosphorylation, with related proteins such as IL2, IL6, and TNFα, which we subsequently submitted to experimental verification.</p></div><div><h3>Conclusion</h3><p>Innovatively stemming from from PCD interactions, in this study, we discerned PCDs with an independent impact on DN: apoptosis and NETotic cell death. We further screened DN evolution- and progression-related biomarkers, i.e. IL33, RPL11, and CX3CR1, all of which we empirically validated. This study not only poroposes a PCD-centric perspective for DN studies but also provides evidence for PCD-mediated immune cell infiltration exploration in DN regulation. Our results could motivate further exploration of DN pathogenesis, such as how the inflammatory microenvironment mediates NETotic cell death in DN regulation, representing a promising direction for fu","PeriodicalId":12521,"journal":{"name":"Genomics","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0888754324001009/pdfft?md5=648ec43a7700b1605e2b94b729fcb8d7&pid=1-s2.0-S0888754324001009-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 : 2024-06-05DOI: 10.1016/j.ygeno.2024.110875
Yuan Jiang , Weiwei Wang , Faqing Tang , Wei Zhang , Sheng Chen , Xiumei Gu , Ping Chen , Xiaoya Xu , Baoning Nian , Zhikuan Li , Chunzhu Chen , Hanbing Yin , Linlin Su , Honghou Sun , Wei Chen , Dadong Zhang , Yuejin Li
Exploration of a stably expressed gene as a reference is critical for the accurate evaluation of miRNAs isolated from small extracellular vesicles (sEVs). In this study, we analyzed small RNA sequencing on plasma sEV miRNAs in the training dataset (n = 104) and found that miR-140-3p was the most stably expressed candidate reference for sEV miRNAs. We further demonstrated that miR-140-3p expressed most stably in the validation cohort (n = 46) when compared to two other reference miRNAs, miR-451a and miR-1228-3p, and the commonly-used miRNA reference U6. Finally, we compared the capability of miR-140-3p and U6 as the internal reference for sEV miRNA expression by evaluating key miRNAs expression in lung cancer patients and found that miR-140-3p was more suitable as a sEV miRNA reference gene. Taken together, our data indicated miR-140-3p as a stable internal reference miRNA of plasma sEVs to evaluate miRNA expression profiles in lung cancer patients.
探索一种稳定表达的基因作为参照物对于准确评估从小细胞外囊泡 (sEV) 分离出来的 miRNA 至关重要。在这项研究中,我们分析了训练数据集中血浆 sEV miRNAs 的小 RNA 测序(n = 104),发现 miR-140-3p 是 sEV miRNAs 中表达最稳定的候选参考基因。我们进一步证明,与另外两个参考 miRNA(miR-451a 和 miR-1228-3p)和常用的 miRNA 参考 U6 相比,miR-140-3p 在验证队列(n = 46)中的表达最稳定。最后,我们通过评估肺癌患者体内关键 miRNA 的表达,比较了 miR-140-3p 和 U6 作为 sEV miRNA 表达内参基因的能力,发现 miR-140-3p 更适合作为 sEV miRNA 的参比基因。综上所述,我们的数据表明 miR-140-3p 是评估肺癌患者血浆 sEV 中 miRNA 表达谱的稳定的内参 miRNA。
{"title":"Identifying MiR-140-3p as a stable internal reference to normalize MicroRNA qRT-PCR levels of plasma small extracellular vesicles in lung cancer patients","authors":"Yuan Jiang , Weiwei Wang , Faqing Tang , Wei Zhang , Sheng Chen , Xiumei Gu , Ping Chen , Xiaoya Xu , Baoning Nian , Zhikuan Li , Chunzhu Chen , Hanbing Yin , Linlin Su , Honghou Sun , Wei Chen , Dadong Zhang , Yuejin Li","doi":"10.1016/j.ygeno.2024.110875","DOIUrl":"10.1016/j.ygeno.2024.110875","url":null,"abstract":"<div><p>Exploration of a stably expressed gene as a reference is critical for the accurate evaluation of miRNAs isolated from small extracellular vesicles (sEVs). In this study, we analyzed small RNA sequencing on plasma sEV miRNAs in the training dataset (<em>n</em> = 104) and found that miR-140-3p was the most stably expressed candidate reference for sEV miRNAs. We further demonstrated that miR-140-3p expressed most stably in the validation cohort (<em>n</em> = 46) when compared to two other reference miRNAs, miR-451a and miR-1228-3p, and the commonly-used miRNA reference U6. Finally, we compared the capability of miR-140-3p and U6 as the internal reference for sEV miRNA expression by evaluating key miRNAs expression in lung cancer patients and found that miR-140-3p was more suitable as a sEV miRNA reference gene. Taken together, our data indicated miR-140-3p as a stable internal reference miRNA of plasma sEVs to evaluate miRNA expression profiles in lung cancer patients.</p></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S088875432400096X/pdfft?md5=74e2661aed946c9deaaf4a5b18727d0e&pid=1-s2.0-S088875432400096X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141288004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 : 2024-06-05DOI: 10.1016/j.ygeno.2024.110876
Jiyuan Zhou , Yuanke Pan , Shubing Wang , Guoqiang Wang , Chengxin Gu , Jinxin Zhu , Zhenlin Tan , Qixian Wu , Weihuang He , Xiaohui Lin , Shu Xu , Kehua Yuan , Ziwen Zheng , Xiaoqing Gong , Chenhao JiangHe , Zhoujian Han , Bingding Huang , Ruyun Ruan , Mingji Feng , Pin Cui , Hui Yang
Timely accurate and cost-efficient detection of colorectal cancer (CRC) is of great clinical importance. This study aims to establish prediction models for detecting CRC using plasma cell-free DNA (cfDNA) fragmentomic features. Whole-genome sequencing (WGS) was performed on cfDNA from 620 participants, including healthy individuals, patients with benign colorectal diseases and CRC patients. Using WGS data, three machine learning methods were compared to build prediction models for the stratification of CRC patients. The optimal model to discriminate CRC patients of all stages from healthy individuals achieved a sensitivity of 92.31% and a specificity of 91.14%, while the model to separate early-stage CRC patients (stage 0-II) from healthy individuals achieved a sensitivity of 88.8% and a specificity of 96.2%. Additionally, the cfDNA fragmentation profiles reflected disease-specific genomic alterations in CRC. Overall, this study suggests that cfDNA fragmentation profiles may potentially become a noninvasive approach for the detection and stratification of CRC.
{"title":"Early detection and stratification of colorectal cancer using plasma cell-free DNA fragmentomic profiling","authors":"Jiyuan Zhou , Yuanke Pan , Shubing Wang , Guoqiang Wang , Chengxin Gu , Jinxin Zhu , Zhenlin Tan , Qixian Wu , Weihuang He , Xiaohui Lin , Shu Xu , Kehua Yuan , Ziwen Zheng , Xiaoqing Gong , Chenhao JiangHe , Zhoujian Han , Bingding Huang , Ruyun Ruan , Mingji Feng , Pin Cui , Hui Yang","doi":"10.1016/j.ygeno.2024.110876","DOIUrl":"10.1016/j.ygeno.2024.110876","url":null,"abstract":"<div><p>Timely accurate and cost-efficient detection of colorectal cancer (CRC) is of great clinical importance. This study aims to establish prediction models for detecting CRC using plasma cell-free DNA (cfDNA) fragmentomic features. Whole-genome sequencing (WGS) was performed on cfDNA from 620 participants, including healthy individuals, patients with benign colorectal diseases and CRC patients. Using WGS data, three machine learning methods were compared to build prediction models for the stratification of CRC patients. The optimal model to discriminate CRC patients of all stages from healthy individuals achieved a sensitivity of 92.31% and a specificity of 91.14%, while the model to separate early-stage CRC patients (stage 0-II) from healthy individuals achieved a sensitivity of 88.8% and a specificity of 96.2%. Additionally, the cfDNA fragmentation profiles reflected disease-specific genomic alterations in CRC. Overall, this study suggests that cfDNA fragmentation profiles may potentially become a noninvasive approach for the detection and stratification of CRC.</p></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0888754324000971/pdfft?md5=9215668aa701ceca2567affa9cc981f2&pid=1-s2.0-S0888754324000971-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141288003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 : 2024-06-03DOI: 10.1016/j.ygeno.2024.110874
Hailiang Song , Tian Dong , Wei Wang , Boyun Jiang , Xiaoyu Yan , Chenfan Geng , Song Bai , Shijian Xu , Hongxia Hu
Low-coverage whole-genome sequencing (LCS) offers a cost-effective alternative for sturgeon breeding, especially given the lack of SNP chips and the high costs associated with whole-genome sequencing. In this study, the efficiency of LCS for genotype imputation and genomic prediction was assessed in 643 sequenced Russian sturgeons (∼13.68×). The results showed that using BaseVar+STITCH at a sequencing depth of 2× with a sample size larger than 300 resulted in the highest genotyping accuracy. In addition, when the sequencing depth reached 0.5× and SNP density was reduced to 50 K through linkage disequilibrium pruning, the prediction accuracy was comparable to that of whole sequencing depth. Furthermore, an incremental feature selection method has the potential to improve prediction accuracy. This study suggests that the combination of LCS and imputation can be a cost-effective strategy, contributing to the genetic improvement of economic traits and promoting genetic gains in aquaculture species.
低覆盖率全基因组测序(LCS)为鲟鱼育种提供了一种具有成本效益的替代方法,特别是考虑到SNP芯片的缺乏和全基因组测序的高成本。本研究评估了 LCS 在 643 条测序后的俄罗斯鲟鱼(∼13.68×)中用于基因型归因和基因组预测的效率。结果表明,在测序深度为 2× 且样本量大于 300 的情况下,使用 BaseVar+STITCH 的基因分型准确率最高。此外,当测序深度达到 0.5× 且通过连接不平衡剪枝将 SNP 密度降低到 50 K 时,预测准确率与全测序深度的预测准确率相当。此外,增量特征选择方法也有可能提高预测准确率。这项研究表明,LCS 与估算相结合是一种经济有效的策略,有助于经济性状的遗传改良,促进水产养殖物种的遗传增殖。
{"title":"Cost-effective genomic prediction of critical economic traits in sturgeons through low-coverage sequencing","authors":"Hailiang Song , Tian Dong , Wei Wang , Boyun Jiang , Xiaoyu Yan , Chenfan Geng , Song Bai , Shijian Xu , Hongxia Hu","doi":"10.1016/j.ygeno.2024.110874","DOIUrl":"https://doi.org/10.1016/j.ygeno.2024.110874","url":null,"abstract":"<div><p>Low-coverage whole-genome sequencing (LCS) offers a cost-effective alternative for sturgeon breeding, especially given the lack of SNP chips and the high costs associated with whole-genome sequencing. In this study, the efficiency of LCS for genotype imputation and genomic prediction was assessed in 643 sequenced Russian sturgeons (∼13.68×). The results showed that using BaseVar+STITCH at a sequencing depth of 2× with a sample size larger than 300 resulted in the highest genotyping accuracy. In addition, when the sequencing depth reached 0.5× and SNP density was reduced to 50 K through linkage disequilibrium pruning, the prediction accuracy was comparable to that of whole sequencing depth. Furthermore, an incremental feature selection method has the potential to improve prediction accuracy. This study suggests that the combination of LCS and imputation can be a cost-effective strategy, contributing to the genetic improvement of economic traits and promoting genetic gains in aquaculture species.</p></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0888754324000958/pdfft?md5=01ca2ae401b39215d97aee9cf1df9f3a&pid=1-s2.0-S0888754324000958-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141249667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 : 2024-05-31DOI: 10.1016/j.ygeno.2024.110873
Fuhong Zhang , Chenbo Shi , Qiuya He , Lu Zhu , Jianqing Zhao , Weiwei Yao , Juan J. Loor , Jun Luo
Goat milk exhibits a robust and distinctive “goaty” flavor. However, the underlying genetic basis of goaty flavor remains elusive and requires further elucidation at the genomic level. Through comparative genomics analysis, we identified divergent signatures of certain proteins in goat, sheep, and cow. MMUT has undergone a goat-specific mutation in the B12 binding domain. We observed the goat FASN exhibits nonsynonymous mutations in the acyltransferase domain. Structural variations in these key proteins may enhance the capacity for synthesizing goaty flavor compounds in goat. Integrated omics analysis revealed the catabolism of branched-chain amino acids contributed to the goat milk flavor. Furthermore, we uncovered a regulatory mechanism in which the transcription factor ZNF281 suppresses the expression of the ECHDC1 gene may play a pivotal role in the accumulation of flavor substances in goat milk. These findings provide insights into the genetic basis underlying the formation of goaty flavor in goat milk.
Statement of significance
Branched-chain fatty acids (BCFAs) play a crucial role in generating the distinctive “goaty” flavor of goat milk. Whether there is an underlying genetic basis associated with goaty flavor is unknown. To begin deciphering mechanisms of goat milk flavor development, we collected transcriptomic data from mammary tissue of goat, sheep, cow, and buffalo at peak lactation for cross-species transcriptome analysis and downloaded nine publicly available genomes for comparative genomic analysis. Our data indicate that the catabolic pathway of branched-chain amino acids (BCAAs) is under positive selection in the goat genome, and most genes involved in this pathway exhibit significantly higher expression levels in goat mammary tissue compared to other species, which contributes to the development of flavor in goat milk. Furthermore, we have elucidated the regulatory mechanism by which the transcription factor ZNF281 suppresses ECHDC1 gene expression, thereby exerting an important influence on the accumulation of flavor compounds in goat milk. These findings provide insights into the genetic mechanisms underlying flavor formation in goat milk and suggest further research to manipulate the flavor of animal products.
{"title":"Integrated analysis of genomics and transcriptomics revealed the genetic basis for goaty flavor formation in goat milk","authors":"Fuhong Zhang , Chenbo Shi , Qiuya He , Lu Zhu , Jianqing Zhao , Weiwei Yao , Juan J. Loor , Jun Luo","doi":"10.1016/j.ygeno.2024.110873","DOIUrl":"10.1016/j.ygeno.2024.110873","url":null,"abstract":"<div><p>Goat milk exhibits a robust and distinctive “goaty” flavor. However, the underlying genetic basis of goaty flavor remains elusive and requires further elucidation at the genomic level. Through comparative genomics analysis, we identified divergent signatures of certain proteins in goat, sheep, and cow. MMUT has undergone a goat-specific mutation in the B12 binding domain. We observed the goat FASN exhibits nonsynonymous mutations in the acyltransferase domain. Structural variations in these key proteins may enhance the capacity for synthesizing goaty flavor compounds in goat. Integrated omics analysis revealed the catabolism of branched-chain amino acids contributed to the goat milk flavor. Furthermore, we uncovered a regulatory mechanism in which the transcription factor ZNF281 suppresses the expression of the <em>ECHDC1</em> gene may play a pivotal role in the accumulation of flavor substances in goat milk. These findings provide insights into the genetic basis underlying the formation of goaty flavor in goat milk.</p></div><div><h3>Statement of significance</h3><p>Branched-chain fatty acids (BCFAs) play a crucial role in generating the distinctive “goaty” flavor of goat milk. Whether there is an underlying genetic basis associated with goaty flavor is unknown. To begin deciphering mechanisms of goat milk flavor development, we collected transcriptomic data from mammary tissue of goat, sheep, cow, and buffalo at peak lactation for cross-species transcriptome analysis and downloaded nine publicly available genomes for comparative genomic analysis. Our data indicate that the catabolic pathway of branched-chain amino acids (BCAAs) is under positive selection in the goat genome, and most genes involved in this pathway exhibit significantly higher expression levels in goat mammary tissue compared to other species, which contributes to the development of flavor in goat milk. Furthermore, we have elucidated the regulatory mechanism by which the transcription factor ZNF281 suppresses <em>ECHDC1</em> gene expression, thereby exerting an important influence on the accumulation of flavor compounds in goat milk. These findings provide insights into the genetic mechanisms underlying flavor formation in goat milk and suggest further research to manipulate the flavor of animal products.</p></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0888754324000946/pdfft?md5=6816c16362c39809dff22288df385927&pid=1-s2.0-S0888754324000946-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141186334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 : 2024-05-29DOI: 10.1016/j.ygeno.2024.110870
Wenxuan Bai , Le Yang , Jing Qiu , Zihan Zhu , Shuxing Wang , Peidi Li , Dawei Zhou , Hongyi Wang , Yuxuan Liao , Yao Yu , Zijiang Yang , Puqiao Wen , Di Zhang
The pathophysiology of atopic dermatitis (AD) is complex. CD4+ T cells play an essential role in the development of lesions in AD. However, the underlying mechanism remains unclear. In the present study, we investigated the differentially expressed genes (DEGs) between adult AD lesioned and non-lesioned skin using two datasets from the Gene Expression Omnibus (GEO) database. 62 DEGs were shown to be related to cytokine response. Compared to non-lesioned skin, lesioned skin showed immune infiltration with increased numbers of activated natural killer (NK) cells and CD4+ T memory cells (p < 0.01). We then identified 13 hub genes with a strong association with CD4+ T cells using weighted correlation network analysis. Single-cell analysis of AD detected a novel CD4+ T subcluster, CD4+ tissue residency memory cells (TRMs), which were verified through immunohistochemistry (IHC) to be increased in the dermal area of AD. The significant relationship between CD4+ TRM and AD was assessed through further analyses. FOXO1 and SBNO2, two of the 13 hub genes, were characteristically expressed in the CD4+ TRM, but down-regulated in IFN-γ/TNF-α-induced HaCaT cells, as shown using quantitative polymerase chain reaction (qPCR). Moreover, SBNO2 expression was associated with increased Th1 infiltration in AD (p < 0.05). In addition, genes filtered using Mendelian randomization were positively correlated with CD4+ TRM and were highly expressed in IFN-γ/TNF-α-induced HaCaT cells, as determined using qPCR and western blotting. Collectively, our results revealed that the newly identified CD4+ TRM may be involved in the pathogenesis of adult AD.
特应性皮炎(AD)的病理生理学非常复杂。CD4+ T 细胞在特应性皮炎的病变发展过程中起着至关重要的作用。然而,其潜在机制仍不清楚。在本研究中,我们利用基因表达总库(GEO)数据库中的两个数据集研究了成人特应性皮炎病变皮肤和非病变皮肤之间的差异表达基因(DEGs)。结果显示,62个DEG与细胞因子反应有关。与无病变皮肤相比,病变皮肤显示出免疫浸润,活化的自然杀伤(NK)细胞和 CD4+ T 记忆细胞(使用加权相关网络分析的 p + T 细胞)数量增加。AD 的单细胞分析检测到了一种新型的 CD4+ T 亚群,即 CD4+ 组织驻留记忆细胞(TRMs),并通过免疫组化(IHC)验证了这种细胞在 AD 的真皮区域有所增加。进一步的分析评估了 CD4+ TRM 与 AD 之间的重要关系。定量聚合酶链反应(qPCR)显示,13 个枢纽基因中的两个基因 FOXO1 和 SBNO2 在 CD4+ TRM 中表达,但在 IFN-γ/TNF-α 诱导的 HaCaT 细胞中却下调。此外,SBNO2 的表达与 AD(p + TRM)中 Th1 细胞浸润的增加有关,并且在 IFN-γ/TNF-α 诱导的 HaCaT 细胞中高表达(使用 qPCR 和 Western 印迹法测定)。总之,我们的研究结果表明,新发现的CD4+ TRM可能参与了成人AD的发病机制。
{"title":"Single-cell analysis of CD4+ tissue residency memory cells (TRMs) in adult atopic dermatitis: A new potential mechanism","authors":"Wenxuan Bai , Le Yang , Jing Qiu , Zihan Zhu , Shuxing Wang , Peidi Li , Dawei Zhou , Hongyi Wang , Yuxuan Liao , Yao Yu , Zijiang Yang , Puqiao Wen , Di Zhang","doi":"10.1016/j.ygeno.2024.110870","DOIUrl":"10.1016/j.ygeno.2024.110870","url":null,"abstract":"<div><p>The pathophysiology of atopic dermatitis (AD) is complex. CD4<sup>+</sup> T cells play an essential role in the development of lesions in AD. However, the underlying mechanism remains unclear. In the present study, we investigated the differentially expressed genes (DEGs) between adult AD lesioned and non-lesioned skin using two datasets from the Gene Expression Omnibus (GEO) database. 62 DEGs were shown to be related to cytokine response. Compared to non-lesioned skin, lesioned skin showed immune infiltration with increased numbers of activated natural killer (NK) cells and CD4<sup>+</sup> T memory cells (<em>p</em> < 0.01). We then identified 13 hub genes with a strong association with CD4<sup>+</sup> T cells using weighted correlation network analysis. Single-cell analysis of AD detected a novel CD4<sup>+</sup> T subcluster, CD4<sup>+</sup> tissue residency memory cells (TRMs), which were verified through immunohistochemistry (IHC) to be increased in the dermal area of AD. The significant relationship between CD4<sup>+</sup> TRM and AD was assessed through further analyses. FOXO1 and SBNO2, two of the 13 hub genes, were characteristically expressed in the CD4<sup>+</sup> TRM, but down-regulated in IFN-γ/TNF-α-induced HaCaT cells, as shown using quantitative polymerase chain reaction (qPCR). Moreover, SBNO2 expression was associated with increased Th1 infiltration in AD (<em>p</em> < 0.05). In addition, genes filtered using Mendelian randomization were positively correlated with CD4<sup>+</sup> TRM and were highly expressed in IFN-γ/TNF-α-induced HaCaT cells, as determined using qPCR and western blotting. Collectively, our results revealed that the newly identified CD4<sup>+</sup> TRM may be involved in the pathogenesis of adult AD.</p></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0888754324000910/pdfft?md5=8c01709a6dbe732533a5bd68d7a74b2c&pid=1-s2.0-S0888754324000910-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141184063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 : 2024-05-26DOI: 10.1016/j.ygeno.2024.110871
Guangrun Yu , Baowang Zhang , Qi Chen , Zequan Huang , Baohong Zhang , Kai Wang , Jinlei Han
Cassava, a crucial tropical crop, faces challenges from cold stress, necessitating an exploration of its molecular response. Here, we investigated the role of DNA methylation in moderating the response to moderate cold stress (10 °C) in cassava. Using whole-genome bisulfite sequencing, we examined DNA methylation patterns in leaf blades and petioles under control conditions, 5 h, and 48 h of cold stress. Tissue-specific responses were observed, with leaf blades exhibiting subtle changes, while petioles displayed a pronounced decrease in methylation levels under cold stress. We identified cold stress-induced differentially methylated regions (DMRs) that demonstrated both tissue and treatment specificity. Importantly, these DMRs were enriched in genes with altered expression, implying functional relevance. The cold-response transcription factor ERF105 associated with DMRs emerged as a significant and conserved regulator across tissues and treatments. Furthermore, we investigated DNA methylation dynamics in transposable elements, emphasizing the sensitivity of MITEs with bHLH binding motifs to cold stress. These findings provide insights into the epigenetic regulation of response to cold stress in cassava, contributing to an understanding of the molecular mechanisms underlying stress adaptation in this tropical plant.
木薯是一种重要的热带作物,面临着冷胁迫的挑战,因此有必要探索其分子响应。在这里,我们研究了DNA甲基化在调节木薯对中度冷胁迫(10 °C)的反应中的作用。利用全基因组亚硫酸氢盐测序技术,我们研究了在对照条件、5 小时和 48 小时冷胁迫条件下叶片和叶柄的 DNA 甲基化模式。观察到了组织特异性反应,叶片表现出微妙的变化,而叶柄在冷胁迫下的甲基化水平明显下降。我们确定了冷胁迫诱导的差异甲基化区域(DMRs),这些区域显示了组织和处理的特异性。重要的是,这些甲基化区域富集在表达发生变化的基因中,这意味着它们具有功能相关性。与DMRs相关的冷反应转录因子ERF105是跨组织和跨处理的重要且保守的调节因子。此外,我们还研究了转座元件的DNA甲基化动态,强调了具有bHLH结合基序的MITE对冷胁迫的敏感性。这些发现深入揭示了木薯对冷胁迫反应的表观遗传调控,有助于了解这种热带植物对胁迫适应的分子机制。
{"title":"Dynamic DNA methylation modifications in the cold stress response of cassava","authors":"Guangrun Yu , Baowang Zhang , Qi Chen , Zequan Huang , Baohong Zhang , Kai Wang , Jinlei Han","doi":"10.1016/j.ygeno.2024.110871","DOIUrl":"10.1016/j.ygeno.2024.110871","url":null,"abstract":"<div><p>Cassava, a crucial tropical crop, faces challenges from cold stress, necessitating an exploration of its molecular response. Here, we investigated the role of DNA methylation in moderating the response to moderate cold stress (10 °C) in cassava. Using whole-genome bisulfite sequencing, we examined DNA methylation patterns in leaf blades and petioles under control conditions, 5 h, and 48 h of cold stress. Tissue-specific responses were observed, with leaf blades exhibiting subtle changes, while petioles displayed a pronounced decrease in methylation levels under cold stress. We identified cold stress-induced differentially methylated regions (DMRs) that demonstrated both tissue and treatment specificity. Importantly, these DMRs were enriched in genes with altered expression, implying functional relevance. The cold-response transcription factor ERF105 associated with DMRs emerged as a significant and conserved regulator across tissues and treatments. Furthermore, we investigated DNA methylation dynamics in transposable elements, emphasizing the sensitivity of MITEs with bHLH binding motifs to cold stress. These findings provide insights into the epigenetic regulation of response to cold stress in cassava, contributing to an understanding of the molecular mechanisms underlying stress adaptation in this tropical plant.</p></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0888754324000922/pdfft?md5=e262674eac04fa817b70bd6048696df7&pid=1-s2.0-S0888754324000922-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}