Dysregulated interactions between host inflammation and gut microbiota over the course of life increase the risk of colorectal cancer(CRC).While environmental factors and socio-economic realities of race remain predom...Dysregulated interactions between host inflammation and gut microbiota over the course of life increase the risk of colorectal cancer(CRC).While environmental factors and socio-economic realities of race remain predominant contributors to CRC disparities in African-Americans(AAs),this review focuses on the biological mediators of CRC disparity,namely the under-appreciated influence of inherited ancestral genetic regulation on mucosal innate immunity and its interaction with the microbiome.There remains a poor understanding of mechanisms linking immune-related genetic polymorphisms and microbiome diversity that could influence chronic inflammation and exacerbate CRC disparities in AAs.A better understanding of the relationship between host genetics,bacteria,and CRC pathogenesis will improve the prediction of cancer risk across race/ethnicity groups overall.展开更多
Whole-exome sequencing(WES)data are frequently used for cancer diagnosis and genome-wide association studies(GWAS),based on high-coverage read mapping,informative variant calling,and high-quality reference genomes.The...Whole-exome sequencing(WES)data are frequently used for cancer diagnosis and genome-wide association studies(GWAS),based on high-coverage read mapping,informative variant calling,and high-quality reference genomes.The center position of the currently used genome assembly,GRCh38,is now challenged by two newly published telomere-to-telomere(T2T)genomes,T2T-CHM13 and T2T-YAO,and it becomes urgent to have a comparative study to test population specificity using the three reference genomes based on real case WES data.Here,we report our analysis along this line for 19 tumor samples collected from Chinese patients.The primary comparison of the exon regions among the three references reveals that the sequences in up to∼1%of target regions in T2T-YAO are widely diversified from GRCh38 and may lead to off-target in sequence capture.However,T2T-YAO still outperforms GRCh38 by obtaining 7.41%of more mapped reads.Due to more reliable read-mapping and closer phylogenetic relationship with the samples than GRCh38,T2T-YAO reduces half of variant calls of clinical significance which are mostly benign,while maintaining sensitivity in identifying pathogenic variants.T2T-YAO also outperforms T2T-CHM13 in reducing calls of Chinese-specific variants.Our findings highlight the critical need for employing population-specific reference genomes in genomic analysis to ensure accurate variant analysis and the significant benefits of tailoring these approaches to the unique genetic background of each ethnic group.展开更多
文摘Dysregulated interactions between host inflammation and gut microbiota over the course of life increase the risk of colorectal cancer(CRC).While environmental factors and socio-economic realities of race remain predominant contributors to CRC disparities in African-Americans(AAs),this review focuses on the biological mediators of CRC disparity,namely the under-appreciated influence of inherited ancestral genetic regulation on mucosal innate immunity and its interaction with the microbiome.There remains a poor understanding of mechanisms linking immune-related genetic polymorphisms and microbiome diversity that could influence chronic inflammation and exacerbate CRC disparities in AAs.A better understanding of the relationship between host genetics,bacteria,and CRC pathogenesis will improve the prediction of cancer risk across race/ethnicity groups overall.
基金supported by grants from the National Key R&DäProgram of China(Grant No.2021YFC 2301000)the National Science Foundation of China(Grant No.32371537)+2 种基金the Linfen Soft Science Research Project(Grant No.2126)the National and Provincial Key Clinical Specialty Capacity Building Project 2020(Department of the Respiratory Medicine)the Peking University People's Hospital Scientific Research Development Funds(Grant No.RDGS2022-11),China.
文摘Whole-exome sequencing(WES)data are frequently used for cancer diagnosis and genome-wide association studies(GWAS),based on high-coverage read mapping,informative variant calling,and high-quality reference genomes.The center position of the currently used genome assembly,GRCh38,is now challenged by two newly published telomere-to-telomere(T2T)genomes,T2T-CHM13 and T2T-YAO,and it becomes urgent to have a comparative study to test population specificity using the three reference genomes based on real case WES data.Here,we report our analysis along this line for 19 tumor samples collected from Chinese patients.The primary comparison of the exon regions among the three references reveals that the sequences in up to∼1%of target regions in T2T-YAO are widely diversified from GRCh38 and may lead to off-target in sequence capture.However,T2T-YAO still outperforms GRCh38 by obtaining 7.41%of more mapped reads.Due to more reliable read-mapping and closer phylogenetic relationship with the samples than GRCh38,T2T-YAO reduces half of variant calls of clinical significance which are mostly benign,while maintaining sensitivity in identifying pathogenic variants.T2T-YAO also outperforms T2T-CHM13 in reducing calls of Chinese-specific variants.Our findings highlight the critical need for employing population-specific reference genomes in genomic analysis to ensure accurate variant analysis and the significant benefits of tailoring these approaches to the unique genetic background of each ethnic group.
