Genetics最新文献_第8页

CDH-3/Cadherin, YAP-1/YAP and EGL-44/TEAD promote SYX-2/Syntaxin and EFF-1 fusogen-mediated phagosome closure. CDH-3/Cadherin、YAP-1/YAP和EGL-44/TEAD促进SYX-2/Syntaxin和ef -1融合原介导的吞噬体关闭。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-03 DOI: 10.1093/genetics/iyaf182

Alec Whited, Aladin Elkhalil, Ginger Clark, Piya Ghose

{"title":"CDH-3/Cadherin, YAP-1/YAP and EGL-44/TEAD promote SYX-2/Syntaxin and EFF-1 fusogen-mediated phagosome closure.","authors":"Alec Whited, Aladin Elkhalil, Ginger Clark, Piya Ghose","doi":"10.1093/genetics/iyaf182","DOIUrl":"10.1093/genetics/iyaf182","url":null,"abstract":"Physical interactions between cells can profoundly impact cell fate. A vital cell fate for normal development and homeostasis is programmed cell death. Cells fated to die must be efficiently cleared via phagocytosis, with defects associated with a variety of diseases. How cell-cell physical associations affect programmed cell elimination is not fully understood. Here we describe, in vivo, a cell-cell adhesion-driven signaling pathway that ensures compartment-specific cell clearance. We previously described the specialized cell death program \"Compartmentalized Cell Elimination\" (CCE) in the C. elegans embryo. During CCE, the tail-spike scaffolding cell (TSC), a polarized epithelial cell with a posteriorly-directed process, is eliminated via an ordered death sequence. The TSC scaffolds the tail tip, formed by the hyp10 epithelial cell, which in turn serves as the phagocyte for the dying TSC process. We have previously provided mechanistic insights into the poorly understood step of phagocytosis, phagosome sealing, reporting that the fusogen EFF-1 helps clear the TSC process specifically. We identify here a genetic pathway that promotes the translocation of EFF-1 to sealing sites. We identify an upstream role for cell-cell physical association and signaling via the cadherin CDH-3, followed by new roles for the transcription factors YAP-1/YAP and EGL-44/TEAD in promoting the localization of SYX-2/Syntaxin around the dying TSC remnant. Moreover, we find that SYX-2, known to promote EFF-1's role in wound healing, also promotes EFF-1 translocation to sites of phagosome closure. Our work sheds additional light on phagosome sealing and implicates cell-cell adhesive forces and signaling as important in cell uptake.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144975524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phospholipid biogenesis maintains neuronal integrity during aging and axon regeneration. 磷脂生物发生在衰老和轴突再生过程中维持神经元的完整性。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-03 DOI: 10.1093/genetics/iyaf122

Seungmee Park, Yishi Jin, Andrew D Chisholm

{"title":"Phospholipid biogenesis maintains neuronal integrity during aging and axon regeneration.","authors":"Seungmee Park, Yishi Jin, Andrew D Chisholm","doi":"10.1093/genetics/iyaf122","DOIUrl":"10.1093/genetics/iyaf122","url":null,"abstract":"Neurons maintain their morphology over prolonged periods of adult life with limited regenerative capacity. Among the various factors that shape neuronal morphology, lipids function as membrane components, signaling molecules, and regulators of synaptic plasticity. Here, we tested genes involved in phospholipid biosynthesis and identified their roles in axon regrowth and maintenance. CEPT-2 and EPT-1 are enzymes catalyzing the final steps in the de novo phospholipid synthesis (Kennedy) pathway. Loss of function mutants of cept-2 or ept-1 show reduced axon regrowth and failure to maintain axon morphology. We demonstrate that CEPT-2 is required cell-autonomously to prevent age-related axonal morphology defects. We further investigated genetic interactions of cept-2 or ept-1 with dip-2, a conserved regulator of lipid metabolism that affects axon morphology maintenance and regrowth after injury. Loss-of-function in dip-2 led to suppression of axon regrowth defects observed in either cept-2 or ept-2 mutants, suggesting that DIP-2 acts to counterbalance phospholipid synthesis. Our findings reveal the genetic regulation of lipid metabolism as critical for axon maintenance following injury and during aging.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144486746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","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 deubiquitinase USP36 funtions through catalytic-dependent and catalytic-independent mechanisms in Drosophila. 果蝇去泛素酶USP36通过催化依赖性和催化非依赖性机制发挥作用。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-03 DOI: 10.1093/genetics/iyaf131

Carmen Coirry, Julie Manessier, Charlène Clot, Magda Mortier, Marie-Odile Fauvarque, Emmanuel Taillebourg

{"title":"The deubiquitinase USP36 funtions through catalytic-dependent and catalytic-independent mechanisms in Drosophila.","authors":"Carmen Coirry, Julie Manessier, Charlène Clot, Magda Mortier, Marie-Odile Fauvarque, Emmanuel Taillebourg","doi":"10.1093/genetics/iyaf131","DOIUrl":"10.1093/genetics/iyaf131","url":null,"abstract":"Deubiquitinases (DUBs) form a specific class of proteases removing ubiquitin from target proteins. They are involved in the regulation of many cellular processes including cell growth and proliferation. Among them, USP36 is a key regulator of the oncogenic transcription factor c-Myc, preventing its degradation by the proteasome. These 2 proteins form an evolutionary conserved complex providing the opportunity to investigate USP36 mechanisms of action in vivo in a genetically tractable model such as Drosophila melanogaster. Null mutants of dUsp36 die early during larval development and exhibit severe growth defects. Strikingly, we report here that flies expressing a catalytically inactive version of dUSP36 produced by CRISPR/Cas9 gene editing survive to adulthood with only minor growth defects, yet males are infertile. This finding indicates that dUSP36 deubiquitinating activity is dispensable for cell growth but essential for spermatogenesis. Our results thus reveal that dUSP36 functions through both catalytic-dependent and catalytic-independent mechanisms, highlighting a dual mode of action with implications for the understanding of DUBs mechanism of action.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144620967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","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 MeCP2 binds to promoters and inhibits transcription in an unmethylated yeast genome. 在未甲基化的酵母基因组中，人类MeCP2与启动子结合并抑制转录。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-03 DOI: 10.1093/genetics/iyaf043

Joshua A R Brown, Maggie Y M Ling, Juan Ausió, LeAnn J Howe

{"title":"Human MeCP2 binds to promoters and inhibits transcription in an unmethylated yeast genome.","authors":"Joshua A R Brown, Maggie Y M Ling, Juan Ausió, LeAnn J Howe","doi":"10.1093/genetics/iyaf043","DOIUrl":"10.1093/genetics/iyaf043","url":null,"abstract":"MeCP2 is a DNA-binding transcriptional regulator that is present at near-histone levels in mammalian cortical neurons. Originally identified as a DNA methylation reader, MeCP2 has been proposed to repress transcription by recruiting corepressors to methylated DNA. While some genome-wide occupancy studies support a preference for methylated DNA, others suggest that MeCP2 binding is more influenced by DNA sequence and accessibility than methylation status. Moreover, multiple studies also suggest a role for MeCP2 in gene activation. To clarify its function, we expressed MeCP2 in Saccharomyces cerevisiae, which lacks DNA methylation and known MeCP2 corepressors. We find that MeCP2 is toxic to yeast and globally inhibits transcription, indicating that MeCP2 can have significant functional impacts without DNA methylation or mammalian corepressors. A subset of MeCP2 mutations that cause the neurodevelopmental disorder Rett syndrome, particularly those that map to the DNA-binding domain, alleviate the toxicity of MeCP2 in yeast. Consistent with the importance of DNA binding for growth inhibition, we show that MeCP2 binds to the yeast genome, with increased occupancy at GC-rich, nucleosome-depleted sequences. These findings present yeast as a useful tool for analyzing MeCP2 and reveal MeCP2 properties that are not strictly dependent on DNA methylation or mammalian corepressors.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of inbreeding on balancing selection: insights from Fisher's geometric model. 近交对平衡选择的影响：来自Fisher几何模型的见解。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-03 DOI: 10.1093/genetics/iyaf128

Colin Olito, Tim Connallon

{"title":"Effects of inbreeding on balancing selection: insights from Fisher's geometric model.","authors":"Colin Olito, Tim Connallon","doi":"10.1093/genetics/iyaf128","DOIUrl":"10.1093/genetics/iyaf128","url":null,"abstract":"Balancing selection is a potentially important factor in the maintenance of genetic variation for fitness and, alongside recessive deleterious mutations, the genetic basis of inbreeding depression. Classic population genetics theory predicts that inbreeding restricts the range of conditions leading to balancing selection. For example, in models of heterozygote advantage, the classic theory shows that inbreeding reduces the parameter conditions for balancing selection by a factor of 1-F, where F is Wright's inbreeding coefficient. However, without a model for the distribution of fitness effects of mutations or genotypes, this classic theory tells us little about the actual probability that new or segregating mutations meet criteria for balancing selection. Here, we develop an extension of Fisher's geometric model with which we explore how inbreeding affects the probability of balancing selection due to heterozygote advantage and its contribution to genetic variance for fitness. When taking the distribution of fitness effects among new, adaptive, and established mutations into account, we find that the prevalence of balancing selection is consistently, and often substantially, below the 1-F baseline implied by classic theory provided that most mutations have phenotypic effects that are small. The reduction is consistently greater for established mutations relative to adaptive mutations, which reinforces the idea that balanced genetic polymorphisms are far more likely to occur in outbred than inbred species. We discuss the implications of our results for studies of genetic variation for fitness and genome scans for signals of balancing selection.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chromosomal translocations are a significant driver of hybrid sterility in rice. 染色体易位是水稻杂交不育的重要驱动因素。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-03 DOI: 10.1093/genetics/iyaf126

Zhenwei Xie, Hai Zheng, Siqi Cheng, Hao Yu, Xiaowen Yu, Chaolong Wang, Jian Wang, Bowen Yao, Xiaokang Jiang, Yang Hu, Anqi Jian, Xiaodong He, Junwen Gao, Minrui Chen, Yun Chen, Yuantao Zhu, Yulong Ren, Zhijun Cheng, Cailin Lei, Qibing Lin, Xin Wang, Xiuping Guo, Yunlu Tian, Shijia Liu, Xi Liu, Ling Jiang, Chuanyin Wu, Shanshan Zhu, Zhigang Zhao, Jianmin Wan

{"title":"Chromosomal translocations are a significant driver of hybrid sterility in rice.","authors":"Zhenwei Xie, Hai Zheng, Siqi Cheng, Hao Yu, Xiaowen Yu, Chaolong Wang, Jian Wang, Bowen Yao, Xiaokang Jiang, Yang Hu, Anqi Jian, Xiaodong He, Junwen Gao, Minrui Chen, Yun Chen, Yuantao Zhu, Yulong Ren, Zhijun Cheng, Cailin Lei, Qibing Lin, Xin Wang, Xiuping Guo, Yunlu Tian, Shijia Liu, Xi Liu, Ling Jiang, Chuanyin Wu, Shanshan Zhu, Zhigang Zhao, Jianmin Wan","doi":"10.1093/genetics/iyaf126","DOIUrl":"10.1093/genetics/iyaf126","url":null,"abstract":"Hybrid sterility is a major barrier in exploiting hybrid vigor in rice grains produced by crossing distantly related parents. While genetic mechanisms such as the killer-protector system have been extensively studied, novel systems underlying hybrid sterility remain poorly characterized. Here, a novel hybrid sterility system governed by two tightly pseudolinked loci SGA1 (on chromosome 1) and SGA2 (on chromosome 2) is reported, which induces semi-sterility in male and female gametes during hybridization between the indica and japonica subspecies. Chromosomal translocations were proposed as the basis for pseudolinkage and unbiased segregation, supported by cytological evidence of meiotic quadrivalent configurations and translocation breakpoint sequences. Gametophytic sterility was identified as the primary driver of dual male-female semi-sterility in translocated heterozygotes. Furthermore, large-segment chromosomal translocations are found to be widespread in rice. Analysis of 120 pangenomic rice accessions revealed that chromosomal translocations are prevalent among cultivars, with one-third exhibiting large translocations (>500 kb). Translocation breakpoints were mainly localized in intergenic and intronic regions, and the disrupted genes were identified as predominantly transposons and retrotransposons. Besides, large translocations were validated through sequence analysis and phenotypic assays. Overall, this study establishes chromosomal translocations as a critical driver of hybrid sterility and provides new insights into heterosis constraints.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144545722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Low mutation rate but high male-bias in the germline of a short-lived opossum. 短寿负鼠种系的低突变率但高雄性偏倚。

IF 5.1 3区生物学

Genetics Pub Date : 2025-09-01 DOI: 10.1093/genetics/iyaf177

Yadira Peña-Garcia, Richard J Wang, Muthuswamy Raveendran, R Alan Harris, Paul B Samollow, Jeffrey Rogers, Matthew W Hahn

{"title":"Low mutation rate but high male-bias in the germline of a short-lived opossum.","authors":"Yadira Peña-Garcia, Richard J Wang, Muthuswamy Raveendran, R Alan Harris, Paul B Samollow, Jeffrey Rogers, Matthew W Hahn","doi":"10.1093/genetics/iyaf177","DOIUrl":"10.1093/genetics/iyaf177","url":null,"abstract":"Age and sex have been found to be important determinants of the mutation rate per generation in mammals, but the mechanisms underlying these factors are still unclear. One approach to distinguishing between alternative mechanisms is to study species that reproduce at very young ages, as competing hypotheses make different predictions about patterns of mutation in these organisms. Here, we study the germline mutation rate in the gray short-tailed opossum, Monodelphis domestica, a laboratory model species that becomes reproductively mature at less than six months of age. Whole-genome sequencing of 22 trios reveals one of the lowest mutation rates per generation found in mammals thus far (0.252 × 10-8 per base pair per generation at an average parental age of 313 days), which is expected given their early reproduction. We also examine the mutation spectrum and find fewer mutations at CpG sites in opossums than in humans, consistent with the lower CpG content in the opossum genome. We observe that two-thirds of mutations are inherited from the male parent in opossums, slightly lower than the degree of male bias observed in organisms that reproduce at much older ages. Nevertheless, the very young age at reproduction in opossums suggests that ongoing spermatogonial divisions in males after puberty are not the primary driver of the observed male mutation bias. These findings contribute to a growing body of evidence that the differences between male and female germline mutation may arise from mechanisms other than cell division post-puberty.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144975497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

AMPK alters proteasome phosphorylation status and prevents persistent proteasome condensates. AMPK改变蛋白酶体磷酸化状态，防止蛋白酶体持续凝聚。

IF 5.1 3区生物学

Genetics Pub Date : 2025-08-29 DOI: 10.1093/genetics/iyaf179

Jianhui Li, Conner Butcher, Kyle VanderVen, Meredith Fitz-Enz, Mark Hochstrasser

{"title":"AMPK alters proteasome phosphorylation status and prevents persistent proteasome condensates.","authors":"Jianhui Li, Conner Butcher, Kyle VanderVen, Meredith Fitz-Enz, Mark Hochstrasser","doi":"10.1093/genetics/iyaf179","DOIUrl":"10.1093/genetics/iyaf179","url":null,"abstract":"Proteasomes are large multiprotein complexes required for selective intracellular protein degradation, regulating numerous cellular processes and maintaining protein homeostasis and organismal health. In the budding yeast Saccharomyces cerevisiae grown under different glucose conditions, proteasomes undergo dynamic phase transitions between free and condensate states concomitant with nucleocytoplasmic translocation. Low glucose-induced cytoplasmic proteasome condensates are usually reversible but become persistent in the absence of AMP-activated protein kinase (AMPK). AMPK is important for proteasome condensate dissolution and proteasome nuclear reimport upon glucose refeeding of quiescent cells. Here we found that AMPK activities and the AMPK signaling pathway affect proteasome subunit phosphorylation, which correlates with the solubility and reversibility of proteasome condensates. Nuclear and cytoplasmic AMPK functions redundantly in proteasome condensate dissolution. AMPK interacts with the proteasome regulatory particle in an AMPK activity-independent manner. At least 50 kinases and phosphatases have been found to associate with the AMPK complex. Therefore, the prevention of persistent proteasome condensate formation by AMPK likely results from regulating the antagonistic effects of downstream kinases and phosphatases on proteasome phosphorylation. A mechanistic understanding of the downstream effector proteins of AMPK that directly regulate proteasome subunit phosphorylation will provide insights into how proteasome phosphorylation is linked to proteasome condensate regulation.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144975512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genotype-by-environment interactions shape ubiquitin-proteasome system activity. 基因型与环境的相互作用形成泛素-蛋白酶体系统活性。

IF 5.1 3区生物学

Genetics Pub Date : 2025-08-29 DOI: 10.1093/genetics/iyaf180

Randi R Avery, Mahlon A Collins, Frank W Albert

{"title":"Genotype-by-environment interactions shape ubiquitin-proteasome system activity.","authors":"Randi R Avery, Mahlon A Collins, Frank W Albert","doi":"10.1093/genetics/iyaf180","DOIUrl":"10.1093/genetics/iyaf180","url":null,"abstract":"In genotype-by-environment interactions (GxE), the effect of a genetic variant on a trait depends on the environment. GxE influences numerous organismal traits. However, we have limited understanding of how GxE shapes molecular processes. Here, we characterized how GxE shapes protein degradation, an essential molecular process that affects cellular and organismal physiology. Using two isolates of the yeast Saccharomyces cerevisiae, we profiled GxE in the ubiquitin-proteasome system (UPS), the primary protein degradation system in eukaryotes. By measuring UPS degradation activity towards six substrates that engage multiple distinct UPS pathways across eight diverse environments, we discovered extensive GxE in the genetics of the UPS. The effects of all environments, including environments previously reported to affect UPS activity, differed between isolates and UPS substrates. To identify genomic regions underlying GxE for UPS activity, we mapped genetic influences on all our environment-UPS substrate combinations. Hundreds of locus effects varied depending on the environment. Most of these corresponded to loci that were present in one environment but not another (\"presence/absence\" GxE), while a smaller number of loci had opposing effects in different environments (\"sign change\" GxE). The number, genomic location, and type of GxE (presence/absence or sign change) of loci exhibiting GxE varied across UPS substrates. Loci exhibiting GxE were clustered at genomic regions that contain core UPS genes and at regions containing variation that affects the expression of thousands of genes, suggesting indirect contributions to UPS activity. Our results reveal complex interactions between the environment and the genetics of protein degradation.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144975453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reflection Knockoffs via Householder Reflection: Applications in Proteomics and Genetic Fine Mapping. 通过户主反射的反射仿制品：在蛋白质组学和遗传精细定位中的应用。

IF 5.1 3区生物学

Genetics Pub Date : 2025-08-29 DOI: 10.1093/genetics/iyaf178

Yongtao Guan, Daniel Levy

{"title":"Reflection Knockoffs via Householder Reflection: Applications in Proteomics and Genetic Fine Mapping.","authors":"Yongtao Guan, Daniel Levy","doi":"10.1093/genetics/iyaf178","DOIUrl":"10.1093/genetics/iyaf178","url":null,"abstract":"We present a novel knockoff construction method, and demonstrate its superior performance in two applications: identifying proteomic signatures of age and genetic fine mapping. Both applications involve datasets of highly correlated features, but they differ in the abundance of driver associations. Our primary contribution is the invention of the reflection knockoff, which is constructed from mirror images - obtained via Householder reflection - of the original features. The reflection knockoffs substantially outperform Model-X knockoffs in feature selection, particularly when features are highly correlated. Our secondary contribution is a simple method to aggregate multiple sets of identically distributed knockoff statistics to improve the consistency of knockoff filters. In the study of proteomic signatures of age, single feature tests showed overly abundant proteomic association with age. Knockoff filters using reflection knockoffs and aggregation, however, revealed that a majority of these associations are hitchhikers instead of drivers. When applied to genetic fine mapping, knockoff filters using reflection knockoffs and aggregation outperform a state-of-the-art method. We discuss a potentially exciting application of reflection knockoffs: sharing genetic data without raising concerns about privacy and regulatory violations.","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144975576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0