Genomic selection is more and more popular in animal and plant breeding industries all around the world, as it can be applied early in life without impacting selection candidates. The objective of this study was to br...Genomic selection is more and more popular in animal and plant breeding industries all around the world, as it can be applied early in life without impacting selection candidates. The objective of this study was to bring the advantages of genomic selection to scallop breeding. Two different genomic selection tools Mix P and gsbay were applied on genomic evaluation of simulated data and Zhikong scallop(Chlamys farreri) field data. The data were compared with genomic best linear unbiased prediction(GBLUP) method which has been applied widely. Our results showed that both Mix P and gsbay could accurately estimate single-nucleotide polymorphism(SNP) marker effects, and thereby could be applied for the analysis of genomic estimated breeding values(GEBV). In simulated data from different scenarios, the accuracy of GEBV acquired was ranged from 0.20 to 0.78 by Mix P; it was ranged from 0.21 to 0.67 by gsbay; and it was ranged from 0.21 to 0.61 by GBLUP. Estimations made by Mix P and gsbay were expected to be more reliable than those estimated by GBLUP. Predictions made by gsbay were more robust, while with Mix P the computation is much faster, especially in dealing with large-scale data. These results suggested that both algorithms implemented by Mix P and gsbay are feasible to carry out genomic selection in scallop breeding, and more genotype data will be necessary to produce genomic estimated breeding values with a higher accuracy for the industry.展开更多
This study employs data-driven approaches to analyze single-cell transcriptomic differences between male and female subjects in subpopulations of peripheral blood mononuclear cells(PBMCs).Applying a RandomForestRegres...This study employs data-driven approaches to analyze single-cell transcriptomic differences between male and female subjects in subpopulations of peripheral blood mononuclear cells(PBMCs).Applying a RandomForestRegressor,we observed consistent model performance across different samples.We reveal significant sex differences in PBMC subpopulations,most notably in four cell types:CD4^(+)Th2,CD8^(+)naïve T,CD4^(+)memory Treg,and CD4^(+)Th1/17 cells.展开更多
In spite of continuous research efforts directed at early detection and treatment of pancreatic cancer, the outlook for patients affected by the disease remains dismal. With most cases still being diagnosed at advance...In spite of continuous research efforts directed at early detection and treatment of pancreatic cancer, the outlook for patients affected by the disease remains dismal. With most cases still being diagnosed at advanced stages, no improvement in survival prognosis is achieved with current diagnostic imaging approaches. In the absence of a dominant precancerous condition, several risk factors have been identified including family history, chronic pancreatitis, smoking, diabetes mellitus, as well as certain genetic disorders such as hereditary pancreatitis, cystic fibrosis, familial atypical multiple mole melanoma, and Peutz-Jeghers and Lynch syn- dromes. Most pancreatic carcinomas, however, remain sporadic. Current progress in experimental molecular techniques has enabled detailed understanding of the molecular processes of pancreatic cancer development. According to the latest information, malignant pancre- atic transformation involves multiple oncogenes and tumor-suppressor genes that are involved in a variety of signaling pathways. The most characteristic aberrations （somatic point mutations and allelic losses） affect onco- genes and tumor-suppressor genes within RAS, AK-I- and Wnt signaling, and have a key role in transcription and proliferation, as well as systems that regulate the cell cycle （SMAD/DPC, CDKN2A/p16） and apoptosis （TP53）. Understanding of the underlying molecular mechanisms should promote development of new methodology for early diagnosis and facilitate improvement in current approaches for pancreatic cancer treatment.展开更多
Genetic factors play an important role in the etiology of inflammatory bowel disease(IBD). The launch of genome-wide association study(GWAS) represents a landmark in the genetic study of human complex disease. Concurr...Genetic factors play an important role in the etiology of inflammatory bowel disease(IBD). The launch of genome-wide association study(GWAS) represents a landmark in the genetic study of human complex disease. Concurrently, computational methods have undergone rapid development during the past a few years, which led to the identification of numerous disease susceptibility loci. IBD is one of the successful examples of GWAS and related analyses. A total of 163 genetic loci and multiple signaling pathways have been identified to be associated with IBD. Pleiotropic effects were found for many of these loci; and risk prediction models were built based on a broad spectrum of genetic variants. Important gene-gene, gene-environment interactions and key contributions of gut microbiome are being discovered. Here we will review the different types of analyses that have been applied to IBD genetic study, discuss the computational methods for each type of analysis, and summarize the discoveries made in IBD research with the application of these methods.展开更多
Approaches to understanding the genetic contribution to inflammatory bowel disease(IBD)have continuously evolved from family-and population-based epidemiology,to linkage analysis,and most recently,to genome-wide assoc...Approaches to understanding the genetic contribution to inflammatory bowel disease(IBD)have continuously evolved from family-and population-based epidemiology,to linkage analysis,and most recently,to genome-wide association studies(GWAS).The next stage in this evolution seems to be the sequencing of the exome,that is,the regions of the human genome which encode proteins.The GWAS approach has been very fruitful in identifying at least 163 loci as being associated with IBD,and now,exome sequencing promises to take our genetic understanding to the next level.In this review we will discuss the possible contributions that can be made by an exome sequencing approach both at the individual patient level to aid with disease diagnosis and future therapies,as well as in advancing knowledge of the pathogenesis of IBD.展开更多
Dear Editor:Central nervous system tumors in the brain or spine are the most common solid tumors in children,which accounts for about 25%of cancers in children younger than 15 years of age,and are the most common caus...Dear Editor:Central nervous system tumors in the brain or spine are the most common solid tumors in children,which accounts for about 25%of cancers in children younger than 15 years of age,and are the most common cause of cancer deaths in children[1].The 5-year survival rate for central nervous system neoplasms has increased dramatically to 74%for patients under 18 years old(97%for benign/borderline malignant tumors)in 2022,compared to 20%in the 1970s[1].Without cure treatments and specific medications for many brain cancers,the dramatic increase of survival rate is largely due to improved hospital care and availability of clinical resources.The length of hospitalization of pediatric patients with brain cancer is an important indicator of prognosis as it reflects the required medical effort needed to care for these patients.The length of hospitalization is also critical for the healthcare system as hospital admission is a part of the care trajectory of the respective patients,related to the cost of medical care[2,3].展开更多
Childhood solid tumors represent a significant public health challenge worldwide,with approximately 15,000 new cases annually in the United States and an estimated 300,000 globally.Down syndrome(DS),a genetic disorder...Childhood solid tumors represent a significant public health challenge worldwide,with approximately 15,000 new cases annually in the United States and an estimated 300,000 globally.Down syndrome(DS),a genetic disorder characterized by an extra full or partial copy of chromosome 21,results in distinctive developmental and physical features.Notably,individuals with DS exhibit a remarkable resilience against solid tumors compared to the general population,with an overall standardized incidence ratio(SIR)of 0.45,despite their increased susceptibility to hematologic malignancies[1].This paradoxical observation has spurred extensive research aimed at uncovering the biological underpinnings of this natural resistance to solid cancers.Current theories suggest that the overexpression of specific genes on chromosome 21 may confer protective benefits(e.g.RCAN1 contributes to antiangiogenic effects),and alterations in immune system function may enhance apoptosis and DNA repair pathways in individuals with trisomy 21 DS[2].展开更多
Diabetes mellitus is a serious threat to human health.Cyclocarya paliurus(Batal.)Iljinskaja(C.paliurus)is one of the traditional herbal medicine and food in China for treating type 2 diabetes,and the C.paliurus polysa...Diabetes mellitus is a serious threat to human health.Cyclocarya paliurus(Batal.)Iljinskaja(C.paliurus)is one of the traditional herbal medicine and food in China for treating type 2 diabetes,and the C.paliurus polysaccharides(CP)were found to be one of its major functional constituents.This research aimed at investigating the hypoglycemic mechanism for CP.It was found that CP markedly attenuated the symptoms of diabetes,and inhibited the protein expression of Bax,improved the expression of Bcl-2 in pancreas of diabetic rats,normalized hormones secretion and controlled the inflammation which contributed to the regeneration of pancreaticβ-cell and insulin resistance.CP treatment increased the beneficial bacteria genus Ruminococcaceae UCG-005 which was reported to be a key genus for protecting against diabetes,and the fecal short-chain fatty acids levels were elevated.Uric metabolites analysis showed that CP treatment helped to protect with the diabetes by seven significantly improved pathways closely with the nutrition metabolism(amino acids and purine)and energy metabolism(TCA cycle),which could help to build up the intestinal epithelial cell defense for the inflammation associated with the diabetes.Our study highlights the specific mechanism of prebiotics to attenuate diabetes through multi-path of gut microbiota and host metabolism.展开更多
DNA sensing and timely activation of interferon(IFN)-mediated innate immunity are crucial for the defense against DNA virus infections and the clearance of abnormal cells.However,overactivation of immune responses may...DNA sensing and timely activation of interferon(IFN)-mediated innate immunity are crucial for the defense against DNA virus infections and the clearance of abnormal cells.However,overactivation of immune responses may lead to tissue damage and autoimmune diseases;therefore,these processes must be intricately regulated.STING is the key adaptor protein,which is activated by cyclic GMP-AMP,the second messenger derived from cGAS-mediated DNA sensing.Here,we report that CCDC50,a newly identified autophagy receptor,tunes STING-directed type I IFN signaling activity by delivering K63-polyubiquitinated STING to autolysosomes for degradation.Knockout of CCDC50 significantly increases herpes simplex virus 1(HSV-1)-or DNA ligand-induced production of type I IFN and proinflammatory cytokines.Ccdc50-deficient mice show increased production of IFN,decreased viral replication,reduced cell infiltration,and improved survival rates compared with their wild-type littermates when challenged with HSV-1.Remarkably,the expression of CCDC50 is downregulated in systemic lupus erythematosus(SLE),a chronic autoimmune disease.CCDC50 levels are negatively correlated with IFN signaling pathway activation and disease severity in human SLE patients.CCDC50 deficiency potentiates the cGAS-STING-mediated immune response triggered by SLE serum.Thus,our findings reveal the critical role of CCDC50 in the immune regulation of viral infections and autoimmune diseases and provide insights into the therapeutic implications of CCDC50 manipulation.展开更多
To the Editor: Early infantile epileptic encephalopathy 23 (EIEE23;OMIM #615859) is a rare (<1/1,000,000 worldwide) kind of inherited autosomal recessive disorder. Patients with EIEE23 are characterized by in tract...To the Editor: Early infantile epileptic encephalopathy 23 (EIEE23;OMIM #615859) is a rare (<1/1,000,000 worldwide) kind of inherited autosomal recessive disorder. Patients with EIEE23 are characterized by in tractable seizures between 2 and 6 months of age.展开更多
Hypertension is a global problem that affects more than 1 billion people worldwide with the increased prevalence year by year[1,2].It contributes to major impacts on health including morbidity and all-cause mortality,...Hypertension is a global problem that affects more than 1 billion people worldwide with the increased prevalence year by year[1,2].It contributes to major impacts on health including morbidity and all-cause mortality,as well as consumption of substantial health care expenses.Understanding the complex pathophysiology and risk factors involved in the development of elevated blood pressure can help treat the disease to better prevent life-threatening conditions and alleviate the socio-economic burden.The hereditary nature of hypertension relies on that up to 30%of blood pressure variation is due to genetics and an individual’s genetic predisposition to hypertensive disease ranges from 15%to 35%[3].展开更多
The ongoing coronavirus disease(COVID-19)outbreak has posed an extraordinary threat to global public health.Patients with certain underlying medical conditions,such as obesity,hypertension,and diabetes are at increase...The ongoing coronavirus disease(COVID-19)outbreak has posed an extraordinary threat to global public health.Patients with certain underlying medical conditions,such as obesity,hypertension,and diabetes are at increased risk for poor outcome in COVID-19.1 Given the high genetic heritability of the aforementioned conditions,their shared genetic factors may play a crucial role in the severity of COVID-19.Indeed,a recent genome-wide association study(GWAS)of COVID-19 has reported two genomic loci associated with severe COVID-19,indicating a strong genetic influence on the severity of COVID-19.展开更多
基金supported by the National High-Tech R&D Program (863 Program No. 2012AA10A405)the earmarked fund for Modern Agro-industry Technology Research Systemthe National Natural Science Foundation of China (No. 31302182)
文摘Genomic selection is more and more popular in animal and plant breeding industries all around the world, as it can be applied early in life without impacting selection candidates. The objective of this study was to bring the advantages of genomic selection to scallop breeding. Two different genomic selection tools Mix P and gsbay were applied on genomic evaluation of simulated data and Zhikong scallop(Chlamys farreri) field data. The data were compared with genomic best linear unbiased prediction(GBLUP) method which has been applied widely. Our results showed that both Mix P and gsbay could accurately estimate single-nucleotide polymorphism(SNP) marker effects, and thereby could be applied for the analysis of genomic estimated breeding values(GEBV). In simulated data from different scenarios, the accuracy of GEBV acquired was ranged from 0.20 to 0.78 by Mix P; it was ranged from 0.21 to 0.67 by gsbay; and it was ranged from 0.21 to 0.61 by GBLUP. Estimations made by Mix P and gsbay were expected to be more reliable than those estimated by GBLUP. Predictions made by gsbay were more robust, while with Mix P the computation is much faster, especially in dealing with large-scale data. These results suggested that both algorithms implemented by Mix P and gsbay are feasible to carry out genomic selection in scallop breeding, and more genotype data will be necessary to produce genomic estimated breeding values with a higher accuracy for the industry.
基金supported by the Institutional Development Funds from the Children's Hospital of Philadelphia to the Center for Applied Genomics(USA)The Children's Hospital of Philadelphia Endowed Chair in Genomic Research(USA)to Hakon Hakonarson.
文摘This study employs data-driven approaches to analyze single-cell transcriptomic differences between male and female subjects in subpopulations of peripheral blood mononuclear cells(PBMCs).Applying a RandomForestRegressor,we observed consistent model performance across different samples.We reveal significant sex differences in PBMC subpopulations,most notably in four cell types:CD4^(+)Th2,CD8^(+)naïve T,CD4^(+)memory Treg,and CD4^(+)Th1/17 cells.
文摘In spite of continuous research efforts directed at early detection and treatment of pancreatic cancer, the outlook for patients affected by the disease remains dismal. With most cases still being diagnosed at advanced stages, no improvement in survival prognosis is achieved with current diagnostic imaging approaches. In the absence of a dominant precancerous condition, several risk factors have been identified including family history, chronic pancreatitis, smoking, diabetes mellitus, as well as certain genetic disorders such as hereditary pancreatitis, cystic fibrosis, familial atypical multiple mole melanoma, and Peutz-Jeghers and Lynch syn- dromes. Most pancreatic carcinomas, however, remain sporadic. Current progress in experimental molecular techniques has enabled detailed understanding of the molecular processes of pancreatic cancer development. According to the latest information, malignant pancre- atic transformation involves multiple oncogenes and tumor-suppressor genes that are involved in a variety of signaling pathways. The most characteristic aberrations （somatic point mutations and allelic losses） affect onco- genes and tumor-suppressor genes within RAS, AK-I- and Wnt signaling, and have a key role in transcription and proliferation, as well as systems that regulate the cell cycle （SMAD/DPC, CDKN2A/p16） and apoptosis （TP53）. Understanding of the underlying molecular mechanisms should promote development of new methodology for early diagnosis and facilitate improvement in current approaches for pancreatic cancer treatment.
文摘Genetic factors play an important role in the etiology of inflammatory bowel disease(IBD). The launch of genome-wide association study(GWAS) represents a landmark in the genetic study of human complex disease. Concurrently, computational methods have undergone rapid development during the past a few years, which led to the identification of numerous disease susceptibility loci. IBD is one of the successful examples of GWAS and related analyses. A total of 163 genetic loci and multiple signaling pathways have been identified to be associated with IBD. Pleiotropic effects were found for many of these loci; and risk prediction models were built based on a broad spectrum of genetic variants. Important gene-gene, gene-environment interactions and key contributions of gut microbiome are being discovered. Here we will review the different types of analyses that have been applied to IBD genetic study, discuss the computational methods for each type of analysis, and summarize the discoveries made in IBD research with the application of these methods.
基金Supported by A Senior Research Award from the Crohn’s to Cardinale CJColitis Foundation of America to Hakonarson Ha special purpose fund from the Edmunds Family Foundation for Ulcerative Colitis Studies to Baldassano RN
文摘Approaches to understanding the genetic contribution to inflammatory bowel disease(IBD)have continuously evolved from family-and population-based epidemiology,to linkage analysis,and most recently,to genome-wide association studies(GWAS).The next stage in this evolution seems to be the sequencing of the exome,that is,the regions of the human genome which encode proteins.The GWAS approach has been very fruitful in identifying at least 163 loci as being associated with IBD,and now,exome sequencing promises to take our genetic understanding to the next level.In this review we will discuss the possible contributions that can be made by an exome sequencing approach both at the individual patient level to aid with disease diagnosis and future therapies,as well as in advancing knowledge of the pathogenesis of IBD.
基金Institutional Development Funds Children's Hospital of Philadelphia The Children's Hospital of Philadelphia Endowed Chair in Genomic Research。
文摘Dear Editor:Central nervous system tumors in the brain or spine are the most common solid tumors in children,which accounts for about 25%of cancers in children younger than 15 years of age,and are the most common cause of cancer deaths in children[1].The 5-year survival rate for central nervous system neoplasms has increased dramatically to 74%for patients under 18 years old(97%for benign/borderline malignant tumors)in 2022,compared to 20%in the 1970s[1].Without cure treatments and specific medications for many brain cancers,the dramatic increase of survival rate is largely due to improved hospital care and availability of clinical resources.The length of hospitalization of pediatric patients with brain cancer is an important indicator of prognosis as it reflects the required medical effort needed to care for these patients.The length of hospitalization is also critical for the healthcare system as hospital admission is a part of the care trajectory of the respective patients,related to the cost of medical care[2,3].
文摘Childhood solid tumors represent a significant public health challenge worldwide,with approximately 15,000 new cases annually in the United States and an estimated 300,000 globally.Down syndrome(DS),a genetic disorder characterized by an extra full or partial copy of chromosome 21,results in distinctive developmental and physical features.Notably,individuals with DS exhibit a remarkable resilience against solid tumors compared to the general population,with an overall standardized incidence ratio(SIR)of 0.45,despite their increased susceptibility to hematologic malignancies[1].This paradoxical observation has spurred extensive research aimed at uncovering the biological underpinnings of this natural resistance to solid cancers.Current theories suggest that the overexpression of specific genes on chromosome 21 may confer protective benefits(e.g.RCAN1 contributes to antiangiogenic effects),and alterations in immune system function may enhance apoptosis and DNA repair pathways in individuals with trisomy 21 DS[2].
基金supported by the National Natural Science Foundation of China for Distinguished Young Scholars(31825020)the Outstanding Science and Technology Innovation Team Project in Jiangxi Province(20165BCB19001)+3 种基金the Project of Academic Leaders of the Major Disciplines in Jiangxi Province(20162BCB22008)the Young Key Project of Natural Science Foundation of Jiangxi Province(20171ACB21013)the Collaborative Project in Agriculture and Food Field between China and Canada(2017ZJGH0102001)the Research Project of State Key Laboratory of Food Science and Technology(SKLF-ZZA-201611)。
文摘Diabetes mellitus is a serious threat to human health.Cyclocarya paliurus(Batal.)Iljinskaja(C.paliurus)is one of the traditional herbal medicine and food in China for treating type 2 diabetes,and the C.paliurus polysaccharides(CP)were found to be one of its major functional constituents.This research aimed at investigating the hypoglycemic mechanism for CP.It was found that CP markedly attenuated the symptoms of diabetes,and inhibited the protein expression of Bax,improved the expression of Bcl-2 in pancreas of diabetic rats,normalized hormones secretion and controlled the inflammation which contributed to the regeneration of pancreaticβ-cell and insulin resistance.CP treatment increased the beneficial bacteria genus Ruminococcaceae UCG-005 which was reported to be a key genus for protecting against diabetes,and the fecal short-chain fatty acids levels were elevated.Uric metabolites analysis showed that CP treatment helped to protect with the diabetes by seven significantly improved pathways closely with the nutrition metabolism(amino acids and purine)and energy metabolism(TCA cycle),which could help to build up the intestinal epithelial cell defense for the inflammation associated with the diabetes.Our study highlights the specific mechanism of prebiotics to attenuate diabetes through multi-path of gut microbiota and host metabolism.
基金This study is supported by the National Natural Science Foundation of China(#81620108020 to DG and#81801574 to PH)Guangdong Province"Pearl River Talent Plan"Innovation and Entrepreneurship Team Project(2019ZT08Y464 to CL)+1 种基金Shenzhen Science and Technology Program(#JCYJ20200109142201695 and#KQTD20180411143323605 to DG and#JCYJ20190807161415336 to PH)DG is also supported by the Guangdong Zhujiang Talents Programme and the National Ten-thousand Talents Programme.
文摘DNA sensing and timely activation of interferon(IFN)-mediated innate immunity are crucial for the defense against DNA virus infections and the clearance of abnormal cells.However,overactivation of immune responses may lead to tissue damage and autoimmune diseases;therefore,these processes must be intricately regulated.STING is the key adaptor protein,which is activated by cyclic GMP-AMP,the second messenger derived from cGAS-mediated DNA sensing.Here,we report that CCDC50,a newly identified autophagy receptor,tunes STING-directed type I IFN signaling activity by delivering K63-polyubiquitinated STING to autolysosomes for degradation.Knockout of CCDC50 significantly increases herpes simplex virus 1(HSV-1)-or DNA ligand-induced production of type I IFN and proinflammatory cytokines.Ccdc50-deficient mice show increased production of IFN,decreased viral replication,reduced cell infiltration,and improved survival rates compared with their wild-type littermates when challenged with HSV-1.Remarkably,the expression of CCDC50 is downregulated in systemic lupus erythematosus(SLE),a chronic autoimmune disease.CCDC50 levels are negatively correlated with IFN signaling pathway activation and disease severity in human SLE patients.CCDC50 deficiency potentiates the cGAS-STING-mediated immune response triggered by SLE serum.Thus,our findings reveal the critical role of CCDC50 in the immune regulation of viral infections and autoimmune diseases and provide insights into the therapeutic implications of CCDC50 manipulation.
基金the China Postdoctoral Science Foundation (2016M602729 to B. B.)Health Technology Commission of Yunnan Province (2016NS235 to B.B.).
文摘To the Editor: Early infantile epileptic encephalopathy 23 (EIEE23;OMIM #615859) is a rare (<1/1,000,000 worldwide) kind of inherited autosomal recessive disorder. Patients with EIEE23 are characterized by in tractable seizures between 2 and 6 months of age.
基金This work was supported by the National Key Research and Development Program of China(2016YFC1300100)the CAMS Innovation Fund for Medical Sciences(2022-I2M-C&T-A-010 and 2022-I2M-C&T-A-011).
文摘Hypertension is a global problem that affects more than 1 billion people worldwide with the increased prevalence year by year[1,2].It contributes to major impacts on health including morbidity and all-cause mortality,as well as consumption of substantial health care expenses.Understanding the complex pathophysiology and risk factors involved in the development of elevated blood pressure can help treat the disease to better prevent life-threatening conditions and alleviate the socio-economic burden.The hereditary nature of hypertension relies on that up to 30%of blood pressure variation is due to genetics and an individual’s genetic predisposition to hypertensive disease ranges from 15%to 35%[3].
文摘The ongoing coronavirus disease(COVID-19)outbreak has posed an extraordinary threat to global public health.Patients with certain underlying medical conditions,such as obesity,hypertension,and diabetes are at increased risk for poor outcome in COVID-19.1 Given the high genetic heritability of the aforementioned conditions,their shared genetic factors may play a crucial role in the severity of COVID-19.Indeed,a recent genome-wide association study(GWAS)of COVID-19 has reported two genomic loci associated with severe COVID-19,indicating a strong genetic influence on the severity of COVID-19.
