Cell genomics最新文献_第9页

Functional and dynamic profiling of transcript isoforms reveals essential roles of alternative splicing in interferon response. 转录本异构体的功能和动态分析揭示了替代剪接在干扰素反应中的重要作用。

IF 11.1

Cell genomics Pub Date : 2024-10-09 Epub Date: 2024-09-16 DOI: 10.1016/j.xgen.2024.100654

Mahoko Takahashi Ueda, Jun Inamo, Fuyuki Miya, Mihoko Shimada, Kensuke Yamaguchi, Yuta Kochi

{"title":"Functional and dynamic profiling of transcript isoforms reveals essential roles of alternative splicing in interferon response.","authors":"Mahoko Takahashi Ueda, Jun Inamo, Fuyuki Miya, Mihoko Shimada, Kensuke Yamaguchi, Yuta Kochi","doi":"10.1016/j.xgen.2024.100654","DOIUrl":"10.1016/j.xgen.2024.100654","url":null,"abstract":"Type I interferon (IFN-I) plays an important role in the innate immune response through inducing IFN-I-stimulated genes (ISGs). However, how alternative splicing (AS) events, especially over time, affect their function remains poorly understood. We generated an annotation (113,843 transcripts) for IFN-I-stimulated human B cells called isoISG using high-accuracy long-read sequencing data from PacBio Sequel II/IIe. Transcript isoform profiling using isoISG revealed that isoform switching occurred in the early response to IFN-I so that ISGs would gain functional domains (e.g., C4B) or higher protein production (e.g., IRF3). Conversely, isoforms lacking functional domains increased during the late phase of IFN-I response, mainly due to intron retention events. This suggests that isoform switching both triggers and terminates IFN-I responses at the translation and protein levels. Furthermore, genetic variants influencing the isoform ratio of ISGs were associated with immunological and infectious diseases. AS has essential roles in regulating innate immune response and associated diseases.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100654"},"PeriodicalIF":11.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pooled endogenous protein tagging and recruitment for systematic profiling of protein function. 汇集内源蛋白质标记和招募，系统分析蛋白质功能。

IF 11.1

Cell genomics Pub Date : 2024-10-09 Epub Date: 2024-09-09 DOI: 10.1016/j.xgen.2024.100651

Yevgeniy V Serebrenik, Deepak Mani, Timothé Maujean, George M Burslem, Ophir Shalem

{"title":"Pooled endogenous protein tagging and recruitment for systematic profiling of protein function.","authors":"Yevgeniy V Serebrenik, Deepak Mani, Timothé Maujean, George M Burslem, Ophir Shalem","doi":"10.1016/j.xgen.2024.100651","DOIUrl":"10.1016/j.xgen.2024.100651","url":null,"abstract":"The emerging field of induced proximity therapeutics, which involves designing molecules to bring together an effector and target protein-typically to induce target degradation-is rapidly advancing. However, its progress is constrained by the lack of scalable and unbiased tools to explore effector-target protein interactions. We combine pooled endogenous gene tagging using a ligand-binding domain with generic small-molecule-based recruitment to screen for induction of protein proximity. We apply this methodology to identify effectors for degradation in two orthogonal screens: using fluorescence to monitor target levels and a cellular growth that depends on the degradation of an essential protein. Our screens revealed new effector proteins for degradation, including previously established examples, and converged on members of the C-terminal-to-LisH (CTLH) complex. We introduce a platform for pooled induction of endogenous protein-protein interactions to expand our toolset of effector proteins for protein degradation and other forms of induced proximity.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100651"},"PeriodicalIF":11.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Human milk variation is shaped by maternal genetics and impacts the infant gut microbiome. 母乳的变化受母体遗传学的影响，并对婴儿肠道微生物群产生影响。

IF 11.1

Cell genomics Pub Date : 2024-10-09 Epub Date: 2024-09-11 DOI: 10.1016/j.xgen.2024.100638

Kelsey E Johnson, Timothy Heisel, Mattea Allert, Annalee Fürst, Nikhila Yerabandi, Dan Knights, Katherine M Jacobs, Eric F Lock, Lars Bode, David A Fields, Michael C Rudolph, Cheryl A Gale, Frank W Albert, Ellen W Demerath, Ran Blekhman

{"title":"Human milk variation is shaped by maternal genetics and impacts the infant gut microbiome.","authors":"Kelsey E Johnson, Timothy Heisel, Mattea Allert, Annalee Fürst, Nikhila Yerabandi, Dan Knights, Katherine M Jacobs, Eric F Lock, Lars Bode, David A Fields, Michael C Rudolph, Cheryl A Gale, Frank W Albert, Ellen W Demerath, Ran Blekhman","doi":"10.1016/j.xgen.2024.100638","DOIUrl":"10.1016/j.xgen.2024.100638","url":null,"abstract":"Human milk is a complex mix of nutritional and bioactive components that provide complete nourishment for the infant. However, we lack a systematic knowledge of the factors shaping milk composition and how milk variation influences infant health. Here, we characterize relationships between maternal genetics, milk gene expression, milk composition, and the infant fecal microbiome in up to 310 exclusively breastfeeding mother-infant pairs. We identified 482 genetic loci associated with milk gene expression unique to the lactating mammary gland and link these loci to breast cancer risk and human milk oligosaccharide concentration. Integrative analyses uncovered connections between milk gene expression and infant gut microbiome, including an association between the expression of inflammation-related genes with milk interleukin-6 (IL-6) concentration and the abundance of Bifidobacterium and Escherichia in the infant gut. Our results show how an improved understanding of the genetics and genomics of human milk connects lactation biology with maternal and infant health.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100638"},"PeriodicalIF":11.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetic analyses of 104 phenotypes in 20,900 Chinese pregnant women reveal pregnancy-specific discoveries. 对 20900 名中国孕妇的 104 种表型进行基因分析，发现了与妊娠有关的特异性发现。

IF 11.1

Cell genomics Pub Date : 2024-10-09 DOI: 10.1016/j.xgen.2024.100633

Han Xiao, Linxuan Li, Meng Yang, Xinyi Zhang, Jieqiong Zhou, Jingyu Zeng, Yan Zhou, Xianmei Lan, Jiuying Liu, Ying Lin, Yuanyuan Zhong, Xiaoqian Zhang, Lin Wang, Zhongqiang Cao, Panhong Liu, Hong Mei, Mingzhi Cai, Xiaonan Cai, Ye Tao, Yunqing Zhu, Canqing Yu, Liqin Hu, Yu Wang, Yushan Huang, Fengxia Su, Ya Gao, Rui Zhou, Xun Xu, Huanming Yang, Jian Wang, Huanhuan Zhu, Aifen Zhou, Xin Jin

{"title":"Genetic analyses of 104 phenotypes in 20,900 Chinese pregnant women reveal pregnancy-specific discoveries.","authors":"Han Xiao, Linxuan Li, Meng Yang, Xinyi Zhang, Jieqiong Zhou, Jingyu Zeng, Yan Zhou, Xianmei Lan, Jiuying Liu, Ying Lin, Yuanyuan Zhong, Xiaoqian Zhang, Lin Wang, Zhongqiang Cao, Panhong Liu, Hong Mei, Mingzhi Cai, Xiaonan Cai, Ye Tao, Yunqing Zhu, Canqing Yu, Liqin Hu, Yu Wang, Yushan Huang, Fengxia Su, Ya Gao, Rui Zhou, Xun Xu, Huanming Yang, Jian Wang, Huanhuan Zhu, Aifen Zhou, Xin Jin","doi":"10.1016/j.xgen.2024.100633","DOIUrl":"10.1016/j.xgen.2024.100633","url":null,"abstract":"Monitoring biochemical phenotypes during pregnancy is vital for maternal and fetal health, allowing early detection and management of pregnancy-related conditions to ensure safety for both. Here, we conducted a genetic analysis of 104 pregnancy phenotypes in 20,900 Chinese women. The genome-wide association study (GWAS) identified a total of 410 trait-locus associations, with 71.71% reported previously. Among the 116 novel hits for 45 phenotypes, 83 were successfully replicated. Among them, 31 were defined as potentially pregnancy-specific associations, including creatine and HELLPAR and neutrophils and ESR1, with subsequent analysis revealing enrichments in estrogen-related pathways and female reproductive tissues. The partitioning heritability underscored the significant roles of fetal blood, embryoid bodies, and female reproductive organs in pregnancy hematology and birth outcomes. Pathway analysis confirmed the intricate interplay of hormone and immune regulation, metabolism, and cell cycle during pregnancy. This study contributes to the understanding of genetic influences on pregnancy phenotypes and their implications for maternal health.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":"4 10","pages":"100633"},"PeriodicalIF":11.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel insights into the genetic architecture of pregnancy glycemic traits from 14,744 Chinese maternities. 从 14,744 名中国孕产妇身上发现妊娠血糖特征遗传结构的新见解。

IF 11.1

Cell genomics Pub Date : 2024-10-09 DOI: 10.1016/j.xgen.2024.100631

Huanhuan Zhu, Han Xiao, Linxuan Li, Meng Yang, Ying Lin, Jieqiong Zhou, Xinyi Zhang, Yan Zhou, Xianmei Lan, Jiuying Liu, Jingyu Zeng, Lin Wang, Yuanyuan Zhong, Xiaobo Qian, Zhongqiang Cao, Panhong Liu, Hong Mei, Mingzhi Cai, Xiaonan Cai, Zhuangyuan Tang, Liqin Hu, Rui Zhou, Xun Xu, Huanming Yang, Jian Wang, Xin Jin, Aifen Zhou

{"title":"Novel insights into the genetic architecture of pregnancy glycemic traits from 14,744 Chinese maternities.","authors":"Huanhuan Zhu, Han Xiao, Linxuan Li, Meng Yang, Ying Lin, Jieqiong Zhou, Xinyi Zhang, Yan Zhou, Xianmei Lan, Jiuying Liu, Jingyu Zeng, Lin Wang, Yuanyuan Zhong, Xiaobo Qian, Zhongqiang Cao, Panhong Liu, Hong Mei, Mingzhi Cai, Xiaonan Cai, Zhuangyuan Tang, Liqin Hu, Rui Zhou, Xun Xu, Huanming Yang, Jian Wang, Xin Jin, Aifen Zhou","doi":"10.1016/j.xgen.2024.100631","DOIUrl":"10.1016/j.xgen.2024.100631","url":null,"abstract":"Glycemic traits are critical indicators of maternal and fetal health during pregnancy. We performed genetic analysis for five glycemic traits in 14,744 Chinese pregnant women. Our genome-wide association study identified 25 locus-trait associations, including established links between gestational diabetes mellitus (GDM) and the genes CDKAL1 and MTNR1B. Notably, we discovered a novel association between fasting glucose during pregnancy and the ESR1 gene (estrogen receptor), which was validated by an independent study in pregnant women. The ESR1-GDM link was recently reported by the FinnGen project. Our work enhances the findings in East Asian populations and highlights the need for independent studies. Further analyses, including genetic correlation, Mendelian randomization, and transcriptome-wide association studies, provided genetic insights into the relationship between pregnancy glycemic traits and hypertension. Overall, our findings advance the understanding of genetic architecture of pregnancy glycemic traits, especially in East Asian populations.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":"4 10","pages":"100631"},"PeriodicalIF":11.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advances in using non-invasive prenatal testing to study genomics related to maternity. 利用无创产前检测研究与孕产有关的基因组学的进展。

IF 11.1

Cell genomics Pub Date : 2024-10-09 DOI: 10.1016/j.xgen.2024.100677

Xin Jin, Xun Xu, Aifen Zhou, Huanhuan Zhu, Qiyuan Li, Siyang Liu, Siqi Liu, Shujia Huang, Jianguo Zhang, Ting Wang, Hankui Liu

引用次数: 0

Comparative modeling reveals the molecular determinants of aneuploidy fitness cost in a wild yeast model. 比较建模揭示了野生酵母模型中非整倍体健康成本的分子决定因素。

IF 11.1

Cell genomics Pub Date : 2024-10-09 Epub Date: 2024-09-23 DOI: 10.1016/j.xgen.2024.100656

Julie Rojas, James Hose, H Auguste Dutcher, Michael Place, John F Wolters, Chris Todd Hittinger, Audrey P Gasch

{"title":"Comparative modeling reveals the molecular determinants of aneuploidy fitness cost in a wild yeast model.","authors":"Julie Rojas, James Hose, H Auguste Dutcher, Michael Place, John F Wolters, Chris Todd Hittinger, Audrey P Gasch","doi":"10.1016/j.xgen.2024.100656","DOIUrl":"10.1016/j.xgen.2024.100656","url":null,"abstract":"Although implicated as deleterious in many organisms, aneuploidy can underlie rapid phenotypic evolution. However, aneuploidy will be maintained only if the benefit outweighs the cost, which remains incompletely understood. To quantify this cost and the molecular determinants behind it, we generated a panel of chromosome duplications in Saccharomyces cerevisiae and applied comparative modeling and molecular validation to understand aneuploidy toxicity. We show that 74%-94% of the variance in aneuploid strains' growth rates is explained by the cumulative cost of genes on each chromosome, measured for single-gene duplications using a genomic library, along with the deleterious contribution of small nucleolar RNAs (snoRNAs) and beneficial effects of tRNAs. Machine learning to identify properties of detrimental gene duplicates provided no support for the balance hypothesis of aneuploidy toxicity and instead identified gene length as the best predictor of toxicity. Our results present a generalized framework for the cost of aneuploidy with implications for disease biology and evolution.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100656"},"PeriodicalIF":11.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phenome-wide association study in 25,639 pregnant Chinese women reveals loci associated with maternal comorbidities and child health. 对 25 639 名中国孕妇进行的全表型关联研究揭示了与孕产妇合并症和儿童健康相关的基因位点。

IF 11.1

Cell genomics Pub Date : 2024-10-09 DOI: 10.1016/j.xgen.2024.100632

Jintao Guo, Qiwei Guo, Taoling Zhong, Chaoqun Xu, Zhongmin Xia, Hongkun Fang, Qinwei Chen, Ying Zhou, Jieqiong Xie, Dandan Jin, You Yang, Xin Wu, Huanhuan Zhu, Ailing Hour, Xin Jin, Yulin Zhou, Qiyuan Li

{"title":"Phenome-wide association study in 25,639 pregnant Chinese women reveals loci associated with maternal comorbidities and child health.","authors":"Jintao Guo, Qiwei Guo, Taoling Zhong, Chaoqun Xu, Zhongmin Xia, Hongkun Fang, Qinwei Chen, Ying Zhou, Jieqiong Xie, Dandan Jin, You Yang, Xin Wu, Huanhuan Zhu, Ailing Hour, Xin Jin, Yulin Zhou, Qiyuan Li","doi":"10.1016/j.xgen.2024.100632","DOIUrl":"10.1016/j.xgen.2024.100632","url":null,"abstract":"Phenome-wide association studies (PheWAS) have been less focused on maternal diseases and maternal-newborn comorbidities, especially in the Chinese population. To enhance our understanding of the genetic basis of these related diseases, we conducted a PheWAS on 25,639 pregnant women and 14,151 newborns in the Chinese Han population using ultra-low-coverage whole-genome sequence (ulcWGS). We identified 2,883 maternal trait-associated SNPs associated with 26 phenotypes, among which 99.5% were near established genome-wide association study (GWAS) loci. Further refinement delineated these SNPs to 442 unique trait-associated loci (TALs) predicated on linkage disequilibrium R2 > 0.8, revealing that 75.6% demonstrated pleiotropy and 50.9% were located in genes implicated in analogous phenotypes. Notably, we discovered 21 maternal SNPs associated with 35 neonatal phenotypes, including two SNPs associated with identical complications in both mothers and children. These findings underscore the importance of integrating ulcWGS data to enrich the discoveries derived from traditional PheWAS approaches.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":"4 10","pages":"100632"},"PeriodicalIF":11.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The loach haplotype-resolved genome and the identification of Mex3a involved in fish air breathing. 泥鳅单倍型基因组和参与鱼类空气呼吸的 Mex3a 的鉴定。

IF 11.1

Cell genomics Pub Date : 2024-10-09 DOI: 10.1016/j.xgen.2024.100670

Bing Sun, Qingshan Li, Xinxin Xiao, Jianwei Zhang, Ying Zhou, Yuwei Huang, Jian Gao, Xiaojuan Cao

{"title":"The loach haplotype-resolved genome and the identification of Mex3a involved in fish air breathing.","authors":"Bing Sun, Qingshan Li, Xinxin Xiao, Jianwei Zhang, Ying Zhou, Yuwei Huang, Jian Gao, Xiaojuan Cao","doi":"10.1016/j.xgen.2024.100670","DOIUrl":"10.1016/j.xgen.2024.100670","url":null,"abstract":"Fish air breathing is crucial for the transition of vertebrates from water to land. So far, the genes involved in fish air breathing have not been well identified. Here, we performed gene enrichment analysis of positively selected genes (PSGs) in loach (Misgurnus anguillicaudatus, an air-breathing fish) in comparison to Triplophysa tibetana (a non-air-breathing fish), haplotype-resolved genome assembly of the loach, and gene evolutionary analysis of air-breathing and non-air-breathing fishes and found that the PSG mex3a originated from ancient air-breathing fish species. Deletion of Mex3a impaired loach air-breathing capacity by inhibiting angiogenesis through its interaction with T-box transcription factor 20. Mex3a overexpression significantly promoted angiogenesis. Structural analysis and point mutation revealed the critical role of the 201st amino acid in loach Mex3a for angiogenesis. Our findings innovatively indicate that the ancient mex3a is a fish air-breathing gene, which holds significance for understanding fish air breathing and provides a valuable resource for cultivating hypoxia-tolerant fish varieties.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":"4 10","pages":"100670"},"PeriodicalIF":11.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Utilizing non-invasive prenatal test sequencing data for human genetic investigation. 将无创产前检测测序数据用于人类基因调查。

IF 11.1

Cell genomics Pub Date : 2024-10-09 DOI: 10.1016/j.xgen.2024.100669

Siyang Liu, Yanhong Liu, Yuqin Gu, Xingchen Lin, Huanhuan Zhu, Hankui Liu, Zhe Xu, Shiyao Cheng, Xianmei Lan, Linxuan Li, Mingxi Huang, Hao Li, Rasmus Nielsen, Robert W Davies, Anders Albrechtsen, Guo-Bo Chen, Xiu Qiu, Xin Jin, Shujia Huang

{"title":"Utilizing non-invasive prenatal test sequencing data for human genetic investigation.","authors":"Siyang Liu, Yanhong Liu, Yuqin Gu, Xingchen Lin, Huanhuan Zhu, Hankui Liu, Zhe Xu, Shiyao Cheng, Xianmei Lan, Linxuan Li, Mingxi Huang, Hao Li, Rasmus Nielsen, Robert W Davies, Anders Albrechtsen, Guo-Bo Chen, Xiu Qiu, Xin Jin, Shujia Huang","doi":"10.1016/j.xgen.2024.100669","DOIUrl":"10.1016/j.xgen.2024.100669","url":null,"abstract":"Non-invasive prenatal testing (NIPT) employs ultra-low-pass sequencing of maternal plasma cell-free DNA to detect fetal trisomy. Its global adoption has established NIPT as a large human genetic resource for exploring genetic variations and their associations with phenotypes. Here, we present methods for analyzing large-scale, low-depth NIPT data, including customized algorithms and software for genetic variant detection, genotype imputation, family relatedness, population structure inference, and genome-wide association analysis of maternal genomes. Our results demonstrate accurate allele frequency estimation and high genotype imputation accuracy (R2>0.84) for NIPT sequencing depths from 0.1× to 0.3×. We also achieve effective classification of duplicates and first-degree relatives, along with robust principal-component analysis. Additionally, we obtain an R2>0.81 for estimating genetic effect sizes across genotyping and sequencing platforms with adequate sample sizes. These methods offer a robust theoretical and practical foundation for utilizing NIPT data in medical genetic research.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":"4 10","pages":"100669"},"PeriodicalIF":11.1,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0