Cell genomics最新文献_第10页

Rhesus macaque as a model for sex-biased neurological diseases. 将猕猴作为研究性神经疾病的模型。

IF 11.1

Cell genomics Pub Date : 2024-07-10 Epub Date: 2024-06-27 DOI: 10.1016/j.xgen.2024.100585

Leticia Rodríguez-Montes, Henrik Kaessmann

引用次数: 0

Exome-wide evidence of compound heterozygous effects across common phenotypes in the UK Biobank. 英国生物库中常见表型的复合杂合效应的全外显子证据。

IF 11.1

Cell genomics Pub Date : 2024-07-10 Epub Date: 2024-06-28 DOI: 10.1016/j.xgen.2024.100602

Frederik H Lassen, Samvida S Venkatesh, Nikolas Baya, Barney Hill, Wei Zhou, Alex Bloemendal, Benjamin M Neale, Benedikt M Kessler, Nicola Whiffin, Cecilia M Lindgren, Duncan S Palmer

{"title":"Exome-wide evidence of compound heterozygous effects across common phenotypes in the UK Biobank.","authors":"Frederik H Lassen, Samvida S Venkatesh, Nikolas Baya, Barney Hill, Wei Zhou, Alex Bloemendal, Benjamin M Neale, Benedikt M Kessler, Nicola Whiffin, Cecilia M Lindgren, Duncan S Palmer","doi":"10.1016/j.xgen.2024.100602","DOIUrl":"10.1016/j.xgen.2024.100602","url":null,"abstract":"The phenotypic impact of compound heterozygous (CH) variation has not been investigated at the population scale. We phased rare variants (MAF ∼0.001%) in the UK Biobank (UKBB) exome-sequencing data to characterize recessive effects in 175,587 individuals across 311 common diseases. A total of 6.5% of individuals carry putatively damaging CH variants, 90% of which are only identifiable upon phasing rare variants (MAF < 0.38%). We identify six recessive gene-trait associations (p < 1.68 × 10-7) after accounting for relatedness, polygenicity, nearby common variants, and rare variant burden. Of these, just one is discovered when considering homozygosity alone. Using longitudinal health records, we additionally identify and replicate a novel association between bi-allelic variation in ATP2C2 and an earlier age at onset of chronic obstructive pulmonary disease (COPD) (p < 3.58 × 10-8). Genetic phase contributes to disease risk for gene-trait pairs: ATP2C2-COPD (p = 0.000238), FLG-asthma (p = 0.00205), and USH2A-visual impairment (p = 0.0084). We demonstrate the power of phasing large-scale genetic cohorts to discover phenome-wide consequences of compound heterozygosity.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100602"},"PeriodicalIF":11.1,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473139","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

Inverted triplications formed by iterative template switches generate structural variant diversity at genomic disorder loci. 迭代模板切换形成的反向三联体在基因组紊乱位点产生结构变异多样性。

IF 11.1

Cell genomics Pub Date : 2024-07-10 Epub Date: 2024-06-21 DOI: 10.1016/j.xgen.2024.100590

Christopher M Grochowski, Jesse D Bengtsson, Haowei Du, Mira Gandhi, Ming Yin Lun, Michele G Mehaffey, KyungHee Park, Wolfram Höps, Eva Benito, Patrick Hasenfeld, Jan O Korbel, Medhat Mahmoud, Luis F Paulin, Shalini N Jhangiani, James Paul Hwang, Sravya V Bhamidipati, Donna M Muzny, Jawid M Fatih, Richard A Gibbs, Matthew Pendleton, Eoghan Harrington, Sissel Juul, Anna Lindstrand, Fritz J Sedlazeck, Davut Pehlivan, James R Lupski, Claudia M B Carvalho

{"title":"Inverted triplications formed by iterative template switches generate structural variant diversity at genomic disorder loci.","authors":"Christopher M Grochowski, Jesse D Bengtsson, Haowei Du, Mira Gandhi, Ming Yin Lun, Michele G Mehaffey, KyungHee Park, Wolfram Höps, Eva Benito, Patrick Hasenfeld, Jan O Korbel, Medhat Mahmoud, Luis F Paulin, Shalini N Jhangiani, James Paul Hwang, Sravya V Bhamidipati, Donna M Muzny, Jawid M Fatih, Richard A Gibbs, Matthew Pendleton, Eoghan Harrington, Sissel Juul, Anna Lindstrand, Fritz J Sedlazeck, Davut Pehlivan, James R Lupski, Claudia M B Carvalho","doi":"10.1016/j.xgen.2024.100590","DOIUrl":"10.1016/j.xgen.2024.100590","url":null,"abstract":"The duplication-triplication/inverted-duplication (DUP-TRP/INV-DUP) structure is a complex genomic rearrangement (CGR). Although it has been identified as an important pathogenic DNA mutation signature in genomic disorders and cancer genomes, its architecture remains unresolved. Here, we studied the genomic architecture of DUP-TRP/INV-DUP by investigating the DNA of 24 patients identified by array comparative genomic hybridization (aCGH) on whom we found evidence for the existence of 4 out of 4 predicted structural variant (SV) haplotypes. Using a combination of short-read genome sequencing (GS), long-read GS, optical genome mapping, and single-cell DNA template strand sequencing (strand-seq), the haplotype structure was resolved in 18 samples. The point of template switching in 4 samples was shown to be a segment of ∼2.2-5.5 kb of 100% nucleotide similarity within inverted repeat pairs. These data provide experimental evidence that inverted low-copy repeats act as recombinant substrates. This type of CGR can result in multiple conformers generating diverse SV haplotypes in susceptible dosage-sensitive loci.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100590"},"PeriodicalIF":11.1,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141441185","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

Sepsis research: Heterogeneity as a foundation rather than an afterthought. 败血症研究：异质性是基础而非事后考虑。

IF 11.1

Cell genomics Pub Date : 2024-07-10 DOI: 10.1016/j.xgen.2024.100608

Timothy H Ciesielski

引用次数: 0

Mudskipper detects combinatorial RNA binding protein interactions in multiplexed CLIP data. Mudskipper 在多重 CLIP 数据中检测组合 RNA 结合蛋白的相互作用。

IF 11.1

Cell genomics Pub Date : 2024-07-10 Epub Date: 2024-07-01 DOI: 10.1016/j.xgen.2024.100603

Hsuanlin Her, Katherine L Rothamel, Grady G Nguyen, Evan A Boyle, Gene W Yeo

引用次数: 0

Gene-environment interactions within a precision environmental health framework. 精准环境健康框架下的基因-环境相互作用。

IF 11.1

Cell genomics Pub Date : 2024-07-10 Epub Date: 2024-06-25 DOI: 10.1016/j.xgen.2024.100591

Alison A Motsinger-Reif, David M Reif, Farida S Akhtari, John S House, C Ryan Campbell, Kyle P Messier, David C Fargo, Tiffany A Bowen, Srikanth S Nadadur, Charles P Schmitt, Kristianna G Pettibone, David M Balshaw, Cindy P Lawler, Shelia A Newton, Gwen W Collman, Aubrey K Miller, B Alex Merrick, Yuxia Cui, Benedict Anchang, Quaker E Harmon, Kimberly A McAllister, Rick Woychik

{"title":"Gene-environment interactions within a precision environmental health framework.","authors":"Alison A Motsinger-Reif, David M Reif, Farida S Akhtari, John S House, C Ryan Campbell, Kyle P Messier, David C Fargo, Tiffany A Bowen, Srikanth S Nadadur, Charles P Schmitt, Kristianna G Pettibone, David M Balshaw, Cindy P Lawler, Shelia A Newton, Gwen W Collman, Aubrey K Miller, B Alex Merrick, Yuxia Cui, Benedict Anchang, Quaker E Harmon, Kimberly A McAllister, Rick Woychik","doi":"10.1016/j.xgen.2024.100591","DOIUrl":"10.1016/j.xgen.2024.100591","url":null,"abstract":"Understanding the complex interplay of genetic and environmental factors in disease etiology and the role of gene-environment interactions (GEIs) across human development stages is important. We review the state of GEI research, including challenges in measuring environmental factors and advantages of GEI analysis in understanding disease mechanisms. We discuss the evolution of GEI studies from candidate gene-environment studies to genome-wide interaction studies (GWISs) and the role of multi-omics in mediating GEI effects. We review advancements in GEI analysis methods and the importance of large-scale datasets. We also address the translation of GEI findings into precision environmental health (PEH), showcasing real-world applications in healthcare and disease prevention. Additionally, we highlight societal considerations in GEI research, including environmental justice, the return of results to participants, and data privacy. Overall, we underscore the significance of GEI for disease prediction and prevention and advocate for integrating the exposome into PEH omics studies.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100591"},"PeriodicalIF":11.1,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141461133","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

Synthetic DNA barcodes identify singlets in scRNA-seq datasets and evaluate doublet algorithms. 合成 DNA 条形码识别 scRNA-seq 数据集中的单体并评估双体算法。

IF 11.1

Cell genomics Pub Date : 2024-07-10 Epub Date: 2024-06-25 DOI: 10.1016/j.xgen.2024.100592

Ziyang Zhang, Madeline E Melzer, Keerthana M Arun, Hanxiao Sun, Carl-Johan Eriksson, Itai Fabian, Sagi Shaashua, Karun Kiani, Yaara Oren, Yogesh Goyal

{"title":"Synthetic DNA barcodes identify singlets in scRNA-seq datasets and evaluate doublet algorithms.","authors":"Ziyang Zhang, Madeline E Melzer, Keerthana M Arun, Hanxiao Sun, Carl-Johan Eriksson, Itai Fabian, Sagi Shaashua, Karun Kiani, Yaara Oren, Yogesh Goyal","doi":"10.1016/j.xgen.2024.100592","DOIUrl":"10.1016/j.xgen.2024.100592","url":null,"abstract":"Single-cell RNA sequencing (scRNA-seq) datasets contain true single cells, or singlets, in addition to cells that coalesce during the protocol, or doublets. Identifying singlets with high fidelity in scRNA-seq is necessary to avoid false negative and false positive discoveries. Although several methodologies have been proposed, they are typically tested on highly heterogeneous datasets and lack a priori knowledge of true singlets. Here, we leveraged datasets with synthetically introduced DNA barcodes for a hitherto unexplored application: to extract ground-truth singlets. We demonstrated the feasibility of our framework, \"singletCode,\" to evaluate existing doublet detection methods across a range of contexts. We also leveraged our ground-truth singlets to train a proof-of-concept machine learning classifier, which outperformed other doublet detection algorithms. Our integrative framework can identify ground-truth singlets and enable robust doublet detection in non-barcoded datasets.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100592"},"PeriodicalIF":11.1,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141461134","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

Evolutionary and biomedical implications of sex differences in the primate brain transcriptome. 灵长类动物大脑转录组性别差异对进化和生物医学的影响。

IF 11.1

Cell genomics Pub Date : 2024-07-10 Epub Date: 2024-06-27 DOI: 10.1016/j.xgen.2024.100589

Alex R DeCasien, Kenneth L Chiou, Camille Testard, Arianne Mercer, Josué E Negrón-Del Valle, Samuel E Bauman Surratt, Olga González, Michala K Stock, Angelina V Ruiz-Lambides, Melween I Martínez, Susan C Antón, Christopher S Walker, Jérôme Sallet, Melissa A Wilson, Lauren J N Brent, Michael J Montague, Chet C Sherwood, Michael L Platt, James P Higham, Noah Snyder-Mackler

{"title":"Evolutionary and biomedical implications of sex differences in the primate brain transcriptome.","authors":"Alex R DeCasien, Kenneth L Chiou, Camille Testard, Arianne Mercer, Josué E Negrón-Del Valle, Samuel E Bauman Surratt, Olga González, Michala K Stock, Angelina V Ruiz-Lambides, Melween I Martínez, Susan C Antón, Christopher S Walker, Jérôme Sallet, Melissa A Wilson, Lauren J N Brent, Michael J Montague, Chet C Sherwood, Michael L Platt, James P Higham, Noah Snyder-Mackler","doi":"10.1016/j.xgen.2024.100589","DOIUrl":"10.1016/j.xgen.2024.100589","url":null,"abstract":"Humans exhibit sex differences in the prevalence of many neurodevelopmental disorders and neurodegenerative diseases. Here, we generated one of the largest multi-brain-region bulk transcriptional datasets for the rhesus macaque and characterized sex-biased gene expression patterns to investigate the translatability of this species for sex-biased neurological conditions. We identify patterns similar to those in humans, which are associated with overlapping regulatory mechanisms, biological processes, and genes implicated in sex-biased human disorders, including autism. We also show that sex-biased genes exhibit greater genetic variance for expression and more tissue-specific expression patterns, which may facilitate rapid evolution of sex-biased genes. Our findings provide insights into the biological mechanisms underlying sex-biased disease and support the rhesus macaque model for the translational study of these conditions.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100589"},"PeriodicalIF":11.1,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473138","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

Extreme overall mushroom genome expansion in Mycena s.s. irrespective of plant hosts or substrate specializations. 无论植物寄主或基质特异性如何，真菌的蘑菇基因组总体都在极度扩张。

IF 11.1

Cell genomics Pub Date : 2024-07-10 Epub Date: 2024-06-27 DOI: 10.1016/j.xgen.2024.100586

Christoffer Bugge Harder, Shingo Miyauchi, Máté Virágh, Alan Kuo, Ella Thoen, Bill Andreopoulos, Dabao Lu, Inger Skrede, Elodie Drula, Bernard Henrissat, Emmanuelle Morin, Annegret Kohler, Kerrie Barry, Kurt LaButti, Asaf Salamov, Anna Lipzen, Zsolt Merényi, Botond Hegedüs, Petr Baldrian, Martina Stursova, Hedda Weitz, Andy Taylor, Maxim Koriabine, Emily Savage, Igor V Grigoriev, László G Nagy, Francis Martin, Håvard Kauserud

{"title":"Extreme overall mushroom genome expansion in Mycena s.s. irrespective of plant hosts or substrate specializations.","authors":"Christoffer Bugge Harder, Shingo Miyauchi, Máté Virágh, Alan Kuo, Ella Thoen, Bill Andreopoulos, Dabao Lu, Inger Skrede, Elodie Drula, Bernard Henrissat, Emmanuelle Morin, Annegret Kohler, Kerrie Barry, Kurt LaButti, Asaf Salamov, Anna Lipzen, Zsolt Merényi, Botond Hegedüs, Petr Baldrian, Martina Stursova, Hedda Weitz, Andy Taylor, Maxim Koriabine, Emily Savage, Igor V Grigoriev, László G Nagy, Francis Martin, Håvard Kauserud","doi":"10.1016/j.xgen.2024.100586","DOIUrl":"10.1016/j.xgen.2024.100586","url":null,"abstract":"Mycena s.s. is a ubiquitous mushroom genus whose members degrade multiple dead plant substrates and opportunistically invade living plant roots. Having sequenced the nuclear genomes of 24 Mycena species, we find them to defy the expected patterns for fungi based on both their traditionally perceived saprotrophic ecology and substrate specializations. Mycena displayed massive genome expansions overall affecting all gene families, driven by novel gene family emergence, gene duplications, enlarged secretomes encoding polysaccharide degradation enzymes, transposable element (TE) proliferation, and horizontal gene transfers. Mainly due to TE proliferation, Arctic Mycena species display genomes of up to 502 Mbp (2-8× the temperate Mycena), the largest among mushroom-forming Agaricomycetes, indicating a possible evolutionary convergence to genomic expansions sometimes seen in Arctic plants. Overall, Mycena show highly unusual, varied mosaic-like genomic structures adaptable to multiple lifestyles, providing genomic illustration for the growing realization that fungal niche adaptations can be far more fluid than traditionally believed.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100586"},"PeriodicalIF":11.1,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473195","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

SpRY-mediated screens facilitate functional dissection of non-coding sequences at single-base resolution. SpRY 介导的筛选有助于以单碱基分辨率对非编码序列进行功能分析。

IF 11.1

Cell genomics Pub Date : 2024-07-10 Epub Date: 2024-06-17 DOI: 10.1016/j.xgen.2024.100583

Yao Yao, Zhiwei Zhou, Xiaoling Wang, Zhirui Liu, Yixin Zhai, Xiaolin Chi, Jingyi Du, Liheng Luo, Zhigang Zhao, Xiaoyue Wang, Chaoyou Xue, Shuquan Rao

{"title":"SpRY-mediated screens facilitate functional dissection of non-coding sequences at single-base resolution.","authors":"Yao Yao, Zhiwei Zhou, Xiaoling Wang, Zhirui Liu, Yixin Zhai, Xiaolin Chi, Jingyi Du, Liheng Luo, Zhigang Zhao, Xiaoyue Wang, Chaoyou Xue, Shuquan Rao","doi":"10.1016/j.xgen.2024.100583","DOIUrl":"10.1016/j.xgen.2024.100583","url":null,"abstract":"CRISPR mutagenesis screens conducted with SpCas9 and other nucleases have identified certain cis-regulatory elements and genetic variants but at a limited resolution due to the absence of protospacer adjacent motif (PAM) sequences. Here, leveraging the broad targeting scope of the near-PAMless SpRY variant, we have demonstrated that saturated SpRY mutagenesis and base editing screens can faithfully identify functional regulatory elements and essential genetic variants for target gene expression at single-base resolution. We further extended this methodology to investigate a genome-wide association study (GWAS) locus at 10q22.1 associated with a red blood cell trait, where we identified potential enhancers regulating HK1 gene expression, despite not all of these enhancers exhibiting typical chromatin signatures. More importantly, our saturated base editing screens pinpoint multiple causal variants within this locus that would otherwise be missed by Bayesian statistical fine-mapping. Our approach is generally applicable to functional interrogation of all non-coding genomic elements while complementing other high-coverage CRISPR screens.","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100583"},"PeriodicalIF":11.1,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141422072","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