Pub Date : 2024-07-10Epub Date: 2024-06-24DOI: 10.1016/j.xgen.2024.100588
Kar-Tong Tan, Michael K Slevin, Mitchell L Leibowitz, Max Garrity-Janger, Jidong Shan, Heng Li, Matthew Meyerson
Alterations in the structure and location of telomeres are pivotal in cancer genome evolution. Here, we applied both long-read and short-read genome sequencing to assess telomere repeat-containing structures in cancers and cancer cell lines. Using long-read genome sequences that span telomeric repeats, we defined four types of telomere repeat variations in cancer cells: neotelomeres where telomere addition heals chromosome breaks, chromosomal arm fusions spanning telomere repeats, fusions of neotelomeres, and peri-centromeric fusions with adjoined telomere and centromere repeats. These results provide a framework for the systematic study of telomeric repeats in cancer genomes, which could serve as a model for understanding the somatic evolution of other repetitive genomic elements.
{"title":"Neotelomeres and telomere-spanning chromosomal arm fusions in cancer genomes revealed by long-read sequencing.","authors":"Kar-Tong Tan, Michael K Slevin, Mitchell L Leibowitz, Max Garrity-Janger, Jidong Shan, Heng Li, Matthew Meyerson","doi":"10.1016/j.xgen.2024.100588","DOIUrl":"10.1016/j.xgen.2024.100588","url":null,"abstract":"<p><p>Alterations in the structure and location of telomeres are pivotal in cancer genome evolution. Here, we applied both long-read and short-read genome sequencing to assess telomere repeat-containing structures in cancers and cancer cell lines. Using long-read genome sequences that span telomeric repeats, we defined four types of telomere repeat variations in cancer cells: neotelomeres where telomere addition heals chromosome breaks, chromosomal arm fusions spanning telomere repeats, fusions of neotelomeres, and peri-centromeric fusions with adjoined telomere and centromere repeats. These results provide a framework for the systematic study of telomeric repeats in cancer genomes, which could serve as a model for understanding the somatic evolution of other repetitive genomic elements.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141452260","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}
Pub Date : 2024-07-10Epub Date: 2024-06-27DOI: 10.1016/j.xgen.2024.100585
Leticia Rodríguez-Montes, Henrik Kaessmann
Sexual dimorphism, differences between males and females of the same species, is widespread in mammals. However, good animal models to study human sexually dimorphic phenotypes are currently lacking. In this issue, DeCasien et al.1 explore the potential of rhesus macaque as a model for investigating sexually dimorphic traits in the human brain.
{"title":"Rhesus macaque as a model for sex-biased neurological diseases.","authors":"Leticia Rodríguez-Montes, Henrik Kaessmann","doi":"10.1016/j.xgen.2024.100585","DOIUrl":"10.1016/j.xgen.2024.100585","url":null,"abstract":"<p><p>Sexual dimorphism, differences between males and females of the same species, is widespread in mammals. However, good animal models to study human sexually dimorphic phenotypes are currently lacking. In this issue, DeCasien et al.<sup>1</sup> explore the potential of rhesus macaque as a model for investigating sexually dimorphic traits in the human brain.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473196","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}
Pub Date : 2024-07-10Epub Date: 2024-06-28DOI: 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
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.
{"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":"<p><p>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<sup>-7</sup>) 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<sup>-8</sup>). 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.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"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}
Pub Date : 2024-07-10DOI: 10.1016/j.xgen.2024.100608
Timothy H Ciesielski
Our understanding of sepsis has been hampered by the implicit assumption that sepsis is a homogeneous disease. In this issue of Cell Genomics, Burnham et al.1 have started to characterize the genetic variants and regulatory networks that underlie variations in the individual response to sepsis; this may eventually enable targeted intervention development.
{"title":"Sepsis research: Heterogeneity as a foundation rather than an afterthought.","authors":"Timothy H Ciesielski","doi":"10.1016/j.xgen.2024.100608","DOIUrl":"10.1016/j.xgen.2024.100608","url":null,"abstract":"<p><p>Our understanding of sepsis has been hampered by the implicit assumption that sepsis is a homogeneous disease. In this issue of Cell Genomics, Burnham et al.<sup>1</sup> have started to characterize the genetic variants and regulatory networks that underlie variations in the individual response to sepsis; this may eventually enable targeted intervention development.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141592263","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}
Pub Date : 2024-07-10Epub Date: 2024-06-21DOI: 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
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.
{"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":"<p><p>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.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"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}
Pub Date : 2024-07-10Epub Date: 2024-07-01DOI: 10.1016/j.xgen.2024.100603
Hsuanlin Her, Katherine L Rothamel, Grady G Nguyen, Evan A Boyle, Gene W Yeo
The uncovering of protein-RNA interactions enables a deeper understanding of RNA processing. Recent multiplexed crosslinking and immunoprecipitation (CLIP) technologies such as antibody-barcoded eCLIP (ABC) dramatically increase the throughput of mapping RNA binding protein (RBP) binding sites. However, multiplex CLIP datasets are multivariate, and each RBP suffers non-uniform signal-to-noise ratio. To address this, we developed Mudskipper, a versatile computational suite comprising two components: a Dirichlet multinomial mixture model to account for the multivariate nature of ABC datasets and a softmasking approach that identifies and removes non-specific protein-RNA interactions in RBPs with low signal-to-noise ratio. Mudskipper demonstrates superior precision and recall over existing tools on multiplex datasets and supports analysis of repetitive elements and small non-coding RNAs. Our findings unravel splicing outcomes and variant-associated disruptions, enabling higher-throughput investigations into diseases and regulation mediated by RBPs.
{"title":"Mudskipper detects combinatorial RNA binding protein interactions in multiplexed CLIP data.","authors":"Hsuanlin Her, Katherine L Rothamel, Grady G Nguyen, Evan A Boyle, Gene W Yeo","doi":"10.1016/j.xgen.2024.100603","DOIUrl":"10.1016/j.xgen.2024.100603","url":null,"abstract":"<p><p>The uncovering of protein-RNA interactions enables a deeper understanding of RNA processing. Recent multiplexed crosslinking and immunoprecipitation (CLIP) technologies such as antibody-barcoded eCLIP (ABC) dramatically increase the throughput of mapping RNA binding protein (RBP) binding sites. However, multiplex CLIP datasets are multivariate, and each RBP suffers non-uniform signal-to-noise ratio. To address this, we developed Mudskipper, a versatile computational suite comprising two components: a Dirichlet multinomial mixture model to account for the multivariate nature of ABC datasets and a softmasking approach that identifies and removes non-specific protein-RNA interactions in RBPs with low signal-to-noise ratio. Mudskipper demonstrates superior precision and recall over existing tools on multiplex datasets and supports analysis of repetitive elements and small non-coding RNAs. Our findings unravel splicing outcomes and variant-associated disruptions, enabling higher-throughput investigations into diseases and regulation mediated by RBPs.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"PeriodicalIF":11.1,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141494447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-10Epub Date: 2024-06-25DOI: 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
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.
{"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":"<p><p>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.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"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}
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.
单细胞 RNA 测序(scRNA-seq)数据集除了包含真正的单细胞(或称单细胞)外,还包含在测序过程中聚合的细胞(或称双细胞)。在 scRNA-seq 中高保真地识别单细胞是避免假阴性和假阳性发现的必要条件。虽然已经提出了几种方法,但它们通常都是在高度异构的数据集上进行测试,缺乏对真正单体的先验知识。在这里,我们利用带有合成引入的 DNA 条形码的数据集进行了一项迄今为止尚未探索过的应用:提取地面真实单体。我们展示了我们的框架 "singletCode "的可行性,以评估各种情况下的现有双码检测方法。我们还利用我们的地面实况单点来训练一个概念验证机器学习分类器,该分类器的性能优于其他双重检测算法。我们的综合框架可以识别地面实况单字,并在非条码数据集中实现稳健的双字检测。
{"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":"<p><p>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.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"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}
Pub Date : 2024-07-10Epub Date: 2024-06-27DOI: 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
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.
{"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":"<p><p>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.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"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}
Pub Date : 2024-07-10Epub Date: 2024-06-27DOI: 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
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.
{"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":"<p><p>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.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":null,"pages":null},"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}