首页 > 最新文献

Nature genetics最新文献

英文 中文
Genetic architecture reconciles linkage and association studies of complex traits 遗传结构调和了复杂性状的关联研究和相关研究
IF 31.7 1区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2024-10-07 DOI: 10.1038/s41588-024-01940-2
Julia Sidorenko, Baptiste Couvy-Duchesne, Kathryn E. Kemper, Gunn-Helen Moen, Laxmi Bhatta, Bjørn Olav Åsvold, Reedik Mägi, Estonian Biobank Research Team, Alireza Ani, Rujia Wang, Ilja M. Nolte, Lifelines Cohort Study, Scott Gordon, Caroline Hayward, Archie Campbell, Daniel J. Benjamin, David Cesarini, David M. Evans, Michael E. Goddard, Chris S. Haley, David Porteous, Sarah E. Medland, Nicholas G. Martin, Harold Snieder, Andres Metspalu, Kristian Hveem, Ben Brumpton, Peter M. Visscher, Loic Yengo
Linkage studies have successfully mapped loci underlying monogenic disorders, but mostly failed when applied to common diseases. Conversely, genome-wide association studies (GWASs) have identified replicable associations between thousands of SNPs and complex traits, yet capture less than half of the total heritability. In the present study we reconcile these two approaches by showing that linkage signals of height and body mass index (BMI) from 119,000 sibling pairs colocalize with GWAS-identified loci. Concordant with polygenicity, we observed the following: a genome-wide inflation of linkage test statistics; that GWAS results predict linkage signals; and that adjusting phenotypes for polygenic scores reduces linkage signals. Finally, we developed a method using recombination rate-stratified, identity-by-descent sharing between siblings to unbiasedly estimate heritability of height (0.76 ± 0.05) and BMI (0.55 ± 0.07). Our results imply that substantial heritability remains unaccounted for by GWAS-identified loci and this residual genetic variation is polygenic and enriched near these loci. Analyses of height and body mass index in 119,000 sibling pairs show that linkage and genome-wide association signals colocalize. Further analyses suggest that family-based linkage signals are fully consistent with a highly polygenic architecture.
连锁研究成功地绘制了单基因遗传病的基因位点图,但在应用于常见疾病时却大多失败。相反,全基因组关联研究(GWAS)发现了数千个 SNP 与复杂性状之间可复制的关联,但只捕捉到不到一半的总遗传率。在本研究中,我们对这两种方法进行了调和,表明来自 119,000 对同胞的身高和体重指数(BMI)的关联信号与全基因组关联研究(GWAS)确定的位点具有共定位性。与多基因性一致,我们观察到以下几点:全基因组范围内的关联检验统计量膨胀;GWAS 结果可预测关联信号;根据多基因评分调整表型可减少关联信号。最后,我们开发了一种方法,利用同胞间的重组率分层、同源共享来无偏估计身高(0.76 ± 0.05)和体重指数(0.55 ± 0.07)的遗传率。我们的研究结果表明,GWAS 确定的基因位点仍有很大的遗传率没有考虑在内,而这种残余遗传变异是多基因的,并且富集在这些基因位点附近。
{"title":"Genetic architecture reconciles linkage and association studies of complex traits","authors":"Julia Sidorenko, Baptiste Couvy-Duchesne, Kathryn E. Kemper, Gunn-Helen Moen, Laxmi Bhatta, Bjørn Olav Åsvold, Reedik Mägi, Estonian Biobank Research Team, Alireza Ani, Rujia Wang, Ilja M. Nolte, Lifelines Cohort Study, Scott Gordon, Caroline Hayward, Archie Campbell, Daniel J. Benjamin, David Cesarini, David M. Evans, Michael E. Goddard, Chris S. Haley, David Porteous, Sarah E. Medland, Nicholas G. Martin, Harold Snieder, Andres Metspalu, Kristian Hveem, Ben Brumpton, Peter M. Visscher, Loic Yengo","doi":"10.1038/s41588-024-01940-2","DOIUrl":"10.1038/s41588-024-01940-2","url":null,"abstract":"Linkage studies have successfully mapped loci underlying monogenic disorders, but mostly failed when applied to common diseases. Conversely, genome-wide association studies (GWASs) have identified replicable associations between thousands of SNPs and complex traits, yet capture less than half of the total heritability. In the present study we reconcile these two approaches by showing that linkage signals of height and body mass index (BMI) from 119,000 sibling pairs colocalize with GWAS-identified loci. Concordant with polygenicity, we observed the following: a genome-wide inflation of linkage test statistics; that GWAS results predict linkage signals; and that adjusting phenotypes for polygenic scores reduces linkage signals. Finally, we developed a method using recombination rate-stratified, identity-by-descent sharing between siblings to unbiasedly estimate heritability of height (0.76 ± 0.05) and BMI (0.55 ± 0.07). Our results imply that substantial heritability remains unaccounted for by GWAS-identified loci and this residual genetic variation is polygenic and enriched near these loci. Analyses of height and body mass index in 119,000 sibling pairs show that linkage and genome-wide association signals colocalize. Further analyses suggest that family-based linkage signals are fully consistent with a highly polygenic architecture.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"56 11","pages":"2352-2360"},"PeriodicalIF":31.7,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142383640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Multiomic profiling identifies predictors of survival in African American patients with acute myeloid leukemia 多基因组分析确定非裔美国人急性髓性白血病患者的生存预测指标
IF 31.7 1区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2024-10-04 DOI: 10.1038/s41588-024-01929-x
Andrew Stiff, Maarten Fornerod, Bailee N. Kain, Deedra Nicolet, Benjamin J. Kelly, Katherine E. Miller, Krzysztof Mrózek, Isaiah Boateng, Audrey Bollas, Elizabeth A. R. Garfinkle, Omolegho Momoh, Foluke A. Fasola, Hannah O. Olawumi, Nuria Mencia-Trinchant, Jean F. Kloppers, Anne-Cecilia van Marle, Eileen Hu, Saranga Wijeratne, Gregory Wheeler, Christopher J. Walker, Jill Buss, Adrienne Heyrosa, Helee Desai, Andrea Laganson, Ethan Hamp, Yazan Abu-Shihab, Hasan Abaza, Parker Kronen, Sidharth Sen, Megan E. Johnstone, Kate Quinn, Ben Wronowski, Erin Hertlein, Linde A. Miles, Alice S. Mims, Christopher C. Oakes, James S. Blachly, Karilyn T. Larkin, Bethany Mundy-Bosse, Andrew J. Carroll, Bayard L. Powell, Jonathan E. Kolitz, Richard M. Stone, Cassandra Duarte, Diana Abbott, Maria L. Amaya, Craig T. Jordan, Geoffrey L. Uy, Wendy Stock, Kellie J. Archer, Electra D. Paskett, Monica L. Guzman, Ross L. Levine, Kamal Menghrajani, Debyani Chakravarty, Michael F. Berger, Daniel Bottomly, Shannon K. McWeeney, Jeffrey W. Tyner, John C. Byrd, Nathan Salomonis, H. Leighton Grimes, Elaine R. Mardis, Ann-Kathrin Eisfeld
Genomic profiles and prognostic biomarkers in patients with acute myeloid leukemia (AML) from ancestry-diverse populations are underexplored. We analyzed the exomes and transcriptomes of 100 patients with AML with genomically confirmed African ancestry (Black; Alliance) and compared their somatic mutation frequencies with those of 323 self-reported white patients with AML, 55% of whom had genomically confirmed European ancestry (white; BeatAML). Here we find that 73% of 162 gene mutations recurrent in Black patients, including a hitherto unreported PHIP alteration detected in 7% of patients, were found in one white patient or not detected. Black patients with myelodysplasia-related AML were younger than white patients suggesting intrinsic and/or extrinsic dysplasia-causing stressors. On multivariable analyses of Black patients, NPM1 and NRAS mutations were associated with inferior disease-free and IDH1 and IDH2 mutations with reduced overall survival. Inflammatory profiles, cell type distributions and transcriptional profiles differed between Black and white patients with NPM1 mutations. Incorporation of ancestry-specific risk markers into the 2022 European LeukemiaNet genetic risk stratification changed risk group assignment for one-third of Black patients and improved their outcome prediction. Analysis of exomes and transcriptomes from 100 African American patients with acute myeloid leukemia identifies ancestry-related variation in mutation profiles and survival. Refined risk classification suggests clinical relevance of these ancestry-associated differences.
对来自不同血统人群的急性髓性白血病(AML)患者的基因组图谱和预后生物标志物的研究还很不够。我们分析了 100 名经基因组学证实具有非洲血统(黑人;Alliance)的急性髓性白血病患者的外显子组和转录组,并将他们的体细胞突变频率与 323 名自我报告的白人急性髓性白血病患者的体细胞突变频率进行了比较,其中 55% 的患者经基因组学证实具有欧洲血统(白人;BeatAML)。我们在此发现,在黑人患者中复发的 162 个基因突变中,73%(包括在 7% 患者中检测到的迄今未报道的 PHIP 变异)在一名白人患者中发现或未检测到。骨髓增生异常相关急性髓细胞白血病的黑人患者比白人患者年轻,这表明有内在和/或外在导致增生异常的压力因素。对黑人患者进行多变量分析后发现,NPM1和NRAS突变与无病生存率降低有关,而IDH1和IDH2突变与总生存率降低有关。NPM1突变的黑人和白人患者的炎症特征、细胞类型分布和转录特征各不相同。在2022年欧洲白血病网络遗传风险分层中纳入血统特异性风险标记,改变了三分之一黑人患者的风险组别分配,并改善了他们的预后。
{"title":"Multiomic profiling identifies predictors of survival in African American patients with acute myeloid leukemia","authors":"Andrew Stiff, Maarten Fornerod, Bailee N. Kain, Deedra Nicolet, Benjamin J. Kelly, Katherine E. Miller, Krzysztof Mrózek, Isaiah Boateng, Audrey Bollas, Elizabeth A. R. Garfinkle, Omolegho Momoh, Foluke A. Fasola, Hannah O. Olawumi, Nuria Mencia-Trinchant, Jean F. Kloppers, Anne-Cecilia van Marle, Eileen Hu, Saranga Wijeratne, Gregory Wheeler, Christopher J. Walker, Jill Buss, Adrienne Heyrosa, Helee Desai, Andrea Laganson, Ethan Hamp, Yazan Abu-Shihab, Hasan Abaza, Parker Kronen, Sidharth Sen, Megan E. Johnstone, Kate Quinn, Ben Wronowski, Erin Hertlein, Linde A. Miles, Alice S. Mims, Christopher C. Oakes, James S. Blachly, Karilyn T. Larkin, Bethany Mundy-Bosse, Andrew J. Carroll, Bayard L. Powell, Jonathan E. Kolitz, Richard M. Stone, Cassandra Duarte, Diana Abbott, Maria L. Amaya, Craig T. Jordan, Geoffrey L. Uy, Wendy Stock, Kellie J. Archer, Electra D. Paskett, Monica L. Guzman, Ross L. Levine, Kamal Menghrajani, Debyani Chakravarty, Michael F. Berger, Daniel Bottomly, Shannon K. McWeeney, Jeffrey W. Tyner, John C. Byrd, Nathan Salomonis, H. Leighton Grimes, Elaine R. Mardis, Ann-Kathrin Eisfeld","doi":"10.1038/s41588-024-01929-x","DOIUrl":"10.1038/s41588-024-01929-x","url":null,"abstract":"Genomic profiles and prognostic biomarkers in patients with acute myeloid leukemia (AML) from ancestry-diverse populations are underexplored. We analyzed the exomes and transcriptomes of 100 patients with AML with genomically confirmed African ancestry (Black; Alliance) and compared their somatic mutation frequencies with those of 323 self-reported white patients with AML, 55% of whom had genomically confirmed European ancestry (white; BeatAML). Here we find that 73% of 162 gene mutations recurrent in Black patients, including a hitherto unreported PHIP alteration detected in 7% of patients, were found in one white patient or not detected. Black patients with myelodysplasia-related AML were younger than white patients suggesting intrinsic and/or extrinsic dysplasia-causing stressors. On multivariable analyses of Black patients, NPM1 and NRAS mutations were associated with inferior disease-free and IDH1 and IDH2 mutations with reduced overall survival. Inflammatory profiles, cell type distributions and transcriptional profiles differed between Black and white patients with NPM1 mutations. Incorporation of ancestry-specific risk markers into the 2022 European LeukemiaNet genetic risk stratification changed risk group assignment for one-third of Black patients and improved their outcome prediction. Analysis of exomes and transcriptomes from 100 African American patients with acute myeloid leukemia identifies ancestry-related variation in mutation profiles and survival. Refined risk classification suggests clinical relevance of these ancestry-associated differences.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"56 11","pages":"2434-2446"},"PeriodicalIF":31.7,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41588-024-01929-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142369986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Genetic African ancestry modifies the biology of acute myeloid leukemia 非洲裔遗传改变了急性髓性白血病的生物学特性
IF 31.7 1区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2024-10-04 DOI: 10.1038/s41588-024-01869-6
Evelyn M. Jiagge
African American patients were under-represented in the studies that led to the current patient classification system for acute myeloid leukemia (AML). A new in-depth analysis of the genetics of AML in African Americans suggests that this omission has implications for patient care.
非裔美国人患者在研究中的代表性不足,而这些研究促成了目前的急性髓性白血病(AML)患者分类系统。一项关于非裔美国人急性髓性白血病遗传学的新的深入分析表明,这种遗漏对病人护理有影响。
{"title":"Genetic African ancestry modifies the biology of acute myeloid leukemia","authors":"Evelyn M. Jiagge","doi":"10.1038/s41588-024-01869-6","DOIUrl":"10.1038/s41588-024-01869-6","url":null,"abstract":"African American patients were under-represented in the studies that led to the current patient classification system for acute myeloid leukemia (AML). A new in-depth analysis of the genetics of AML in African Americans suggests that this omission has implications for patient care.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"56 11","pages":"2299-2301"},"PeriodicalIF":31.7,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142369985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Population-specific putative causal variants shape quantitative traits 种群特异性推定因果变异塑造数量性状
IF 31.7 1区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2024-10-03 DOI: 10.1038/s41588-024-01913-5
Satoshi Koyama, Xiaoxi Liu, Yoshinao Koike, Keiko Hikino, Masaru Koido, Wei Li, Kotaro Akaki, Kohei Tomizuka, Shuji Ito, Nao Otomo, Hiroyuki Suetsugu, Soichiro Yoshino, Masato Akiyama, Kohei Saito, Yuki Ishikawa, Christian Benner, Pradeep Natarajan, Patrick T. Ellinor, Taisei Mushiroda, Momoko Horikoshi, Masashi Ikeda, Nakao Iwata, Koichi Matsuda, Biobank Japan Project, Shumpei Niida, Kouichi Ozaki, Yukihide Momozawa, Shiro Ikegawa, Osamu Takeuchi, Kaoru Ito, Chikashi Terao
Human genetic variants are associated with many traits through largely unknown mechanisms. Here, combining approximately 260,000 Japanese study participants, a Japanese-specific genotype reference panel and statistical fine-mapping, we identified 4,423 significant loci across 63 quantitative traits, among which 601 were new, and 9,406 putatively causal variants. New associations included Japanese-specific coding, splicing and noncoding variants, exemplified by a damaging missense variant rs730881101 in TNNT2 associated with lower heart function and increased risk for heart failure (P = 1.4 × 10−15 and odds ratio = 4.5, 95% confidence interval = 3.1–6.5). Putative causal noncoding variants were supported by state-of-art in silico functional assays and had comparable effect sizes to coding variants. A plausible example of new mechanisms of causal variants is an enrichment of causal variants in 3′ untranslated regions (UTRs), including the Japanese-specific rs13306436 in IL6 associated with pro-inflammatory traits and protection against tuberculosis. We experimentally showed that transcripts with rs13306436 are resistant to mRNA degradation by regnase-1, an RNA-binding protein. Our study provides a list of fine-mapped causal variants to be tested for functionality and underscores the importance of sequencing, genotyping and association efforts in diverse populations. Genome-wide association and fine-mapping analyses in approximately 260,000 Japanese individuals combined with a newly constructed Japanese-specific genotype reference panel identify hundreds of new loci and putative causal variants for 63 quantitative traits.
人类基因变异与许多性状相关,其机制在很大程度上是未知的。在这里,我们结合约 26 万名日本研究参与者、日本特异性基因型参考面板和统计精细图谱,在 63 个数量性状中发现了 4423 个重要位点,其中 601 个为新位点,9406 个为推测因果变异。新的关联包括日本特异性编码变异、剪接变异和非编码变异,例如 TNNT2 中的一个破坏性错义变异 rs730881101 与心脏功能降低和心力衰竭风险增加有关(P = 1.4 × 10-15 和几率比 = 4.5,95% 置信区间 = 3.1-6.5)。推定的非编码因果变异得到了最先进的硅学功能测试的支持,其效应大小与编码变异相当。因果变异新机制的一个可信例子是,3′非翻译区(UTR)中的因果变异富集,包括日本特异的 IL6 rs13306436,它与促炎症特征和结核病保护相关。我们的实验表明,带有rs13306436的转录本能抵抗RNA结合蛋白regnase-1对mRNA的降解。我们的研究提供了一份待测试功能的精细映射因果变异体列表,并强调了在不同人群中进行测序、基因分型和关联工作的重要性。
{"title":"Population-specific putative causal variants shape quantitative traits","authors":"Satoshi Koyama, Xiaoxi Liu, Yoshinao Koike, Keiko Hikino, Masaru Koido, Wei Li, Kotaro Akaki, Kohei Tomizuka, Shuji Ito, Nao Otomo, Hiroyuki Suetsugu, Soichiro Yoshino, Masato Akiyama, Kohei Saito, Yuki Ishikawa, Christian Benner, Pradeep Natarajan, Patrick T. Ellinor, Taisei Mushiroda, Momoko Horikoshi, Masashi Ikeda, Nakao Iwata, Koichi Matsuda, Biobank Japan Project, Shumpei Niida, Kouichi Ozaki, Yukihide Momozawa, Shiro Ikegawa, Osamu Takeuchi, Kaoru Ito, Chikashi Terao","doi":"10.1038/s41588-024-01913-5","DOIUrl":"10.1038/s41588-024-01913-5","url":null,"abstract":"Human genetic variants are associated with many traits through largely unknown mechanisms. Here, combining approximately 260,000 Japanese study participants, a Japanese-specific genotype reference panel and statistical fine-mapping, we identified 4,423 significant loci across 63 quantitative traits, among which 601 were new, and 9,406 putatively causal variants. New associations included Japanese-specific coding, splicing and noncoding variants, exemplified by a damaging missense variant rs730881101 in TNNT2 associated with lower heart function and increased risk for heart failure (P = 1.4 × 10−15 and odds ratio = 4.5, 95% confidence interval = 3.1–6.5). Putative causal noncoding variants were supported by state-of-art in silico functional assays and had comparable effect sizes to coding variants. A plausible example of new mechanisms of causal variants is an enrichment of causal variants in 3′ untranslated regions (UTRs), including the Japanese-specific rs13306436 in IL6 associated with pro-inflammatory traits and protection against tuberculosis. We experimentally showed that transcripts with rs13306436 are resistant to mRNA degradation by regnase-1, an RNA-binding protein. Our study provides a list of fine-mapped causal variants to be tested for functionality and underscores the importance of sequencing, genotyping and association efforts in diverse populations. Genome-wide association and fine-mapping analyses in approximately 260,000 Japanese individuals combined with a newly constructed Japanese-specific genotype reference panel identify hundreds of new loci and putative causal variants for 63 quantitative traits.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"56 10","pages":"2027-2035"},"PeriodicalIF":31.7,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41588-024-01913-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142368959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Context transcription factors establish cooperative environments and mediate enhancer communication 内涵转录因子建立合作环境并介导增强子交流
IF 31.7 1区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2024-10-03 DOI: 10.1038/s41588-024-01892-7
Judith F. Kribelbauer-Swietek, Olga Pushkarev, Vincent Gardeux, Katerina Faltejskova, Julie Russeil, Guido van Mierlo, Bart Deplancke
Many enhancers control gene expression by assembling regulatory factor clusters, also referred to as condensates. This process is vital for facilitating enhancer communication and establishing cellular identity. However, how DNA sequence and transcription factor (TF) binding instruct the formation of high regulatory factor environments remains poorly understood. Here we developed a new approach leveraging enhancer-centric chromatin accessibility quantitative trait loci (caQTLs) to nominate regulatory factor clusters genome-wide. By analyzing TF-binding signatures within the context of caQTLs and comparing episomal versus endogenous enhancer activities, we discovered a class of regulators, ‘context-only’ TFs, that amplify the activity of cell type-specific caQTL-binding TFs, that is, ‘context-initiator’ TFs. Similar to super-enhancers, enhancers enriched for context-only TF-binding sites display high coactivator binding and sensitivity to bromodomain-inhibiting molecules. We further show that binding sites for context-only and context-initiator TFs underlie enhancer coordination, providing a mechanistic rationale for how a loose TF syntax confers regulatory specificity. This study identifies context-only transcription factors (TFs), a TF class that enhances DNA accessibility initiated by cell type-specific TFs and establishes cooperative environments. Enhancers enriched with motifs of both TF classes show high coactivator binding, enhanced coordination and sensitivity to bromodomain inhibitors.
许多增强子通过组装调控因子簇(也称为凝聚体)来控制基因表达。这一过程对于促进增强子交流和建立细胞特性至关重要。然而,人们对DNA序列和转录因子(TF)结合如何指导高调控因子环境的形成仍然知之甚少。在这里,我们开发了一种新方法,利用以增强子为中心的染色质可及性定量性状位点(caQTLs)在全基因组范围内提名调控因子群。通过分析caQTLs背景下的TF结合特征并比较外显子与内生增强子的活性,我们发现了一类调控因子--"纯背景 "TFs,它们能放大细胞类型特异性caQTL结合TFs(即 "背景启动子 "TFs)的活性。与超级增强子类似,富集了纯上下文TF结合位点的增强子也显示出很高的辅激活子结合率和对溴化链抑制分子的敏感性。我们进一步表明,纯上下文 TF 和上下文启动子 TF 的结合位点是增强子协调的基础,这为松散的 TF 句法如何赋予调控特异性提供了机理依据。
{"title":"Context transcription factors establish cooperative environments and mediate enhancer communication","authors":"Judith F. Kribelbauer-Swietek, Olga Pushkarev, Vincent Gardeux, Katerina Faltejskova, Julie Russeil, Guido van Mierlo, Bart Deplancke","doi":"10.1038/s41588-024-01892-7","DOIUrl":"10.1038/s41588-024-01892-7","url":null,"abstract":"Many enhancers control gene expression by assembling regulatory factor clusters, also referred to as condensates. This process is vital for facilitating enhancer communication and establishing cellular identity. However, how DNA sequence and transcription factor (TF) binding instruct the formation of high regulatory factor environments remains poorly understood. Here we developed a new approach leveraging enhancer-centric chromatin accessibility quantitative trait loci (caQTLs) to nominate regulatory factor clusters genome-wide. By analyzing TF-binding signatures within the context of caQTLs and comparing episomal versus endogenous enhancer activities, we discovered a class of regulators, ‘context-only’ TFs, that amplify the activity of cell type-specific caQTL-binding TFs, that is, ‘context-initiator’ TFs. Similar to super-enhancers, enhancers enriched for context-only TF-binding sites display high coactivator binding and sensitivity to bromodomain-inhibiting molecules. We further show that binding sites for context-only and context-initiator TFs underlie enhancer coordination, providing a mechanistic rationale for how a loose TF syntax confers regulatory specificity. This study identifies context-only transcription factors (TFs), a TF class that enhances DNA accessibility initiated by cell type-specific TFs and establishes cooperative environments. Enhancers enriched with motifs of both TF classes show high coactivator binding, enhanced coordination and sensitivity to bromodomain inhibitors.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"56 10","pages":"2199-2212"},"PeriodicalIF":31.7,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41588-024-01892-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142368958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Pan-African analysis identifies genetic differences in prostate cancer risk 泛非分析确定了前列腺癌风险的基因差异
IF 31.7 1区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2024-10-03 DOI: 10.1038/s41588-024-01932-2
To understand the genetic basis of disease, it is essential to study diverse populations. We conducted the largest study to date of African men to evaluate the evolutionary genetics and causes of prostate cancer. Our findings reveal novel genetic associations, including those that were not observed in studies of non-African populations.
要了解疾病的遗传基础,必须对不同人群进行研究。我们对非洲男性进行了迄今为止最大规模的研究,以评估前列腺癌的进化遗传学和病因。我们的研究结果揭示了新的遗传关联,包括那些在非非洲人群研究中未观察到的关联。
{"title":"Pan-African analysis identifies genetic differences in prostate cancer risk","authors":"","doi":"10.1038/s41588-024-01932-2","DOIUrl":"10.1038/s41588-024-01932-2","url":null,"abstract":"To understand the genetic basis of disease, it is essential to study diverse populations. We conducted the largest study to date of African men to evaluate the evolutionary genetics and causes of prostate cancer. Our findings reveal novel genetic associations, including those that were not observed in studies of non-African populations.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"56 10","pages":"2006-2007"},"PeriodicalIF":31.7,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142369924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Standardizing variant naming in literature with VariantValidator to increase diagnostic rates 利用 VariantValidator 规范文献中的变体命名,提高诊断率
IF 31.7 1区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2024-10-02 DOI: 10.1038/s41588-024-01938-w
Peter J. Freeman, John F. Wagstaff, Ivo F. A. C. Fokkema, Garry R. Cutting, Heidi L. Rehm, Angela C. Davies, Johan T. den Dunnen, Liam J. Gretton, Raymond Dalgleish
Accurate naming of genetic variants is essential to identify clinical data that interpret the consequences of such variants. In partnership with the Human Genome Organization, we advocate for integration of VariantValidator in publishing of journals and databases, to improve the quality of shared genetic data and ultimately patient outcomes.
基因变异的准确命名对于识别解释此类变异后果的临床数据至关重要。我们与人类基因组组织(Human Genome Organization)合作,倡导将 VariantValidator 集成到期刊和数据库的出版中,以提高共享基因数据的质量,最终改善患者的治疗效果。
{"title":"Standardizing variant naming in literature with VariantValidator to increase diagnostic rates","authors":"Peter J. Freeman, John F. Wagstaff, Ivo F. A. C. Fokkema, Garry R. Cutting, Heidi L. Rehm, Angela C. Davies, Johan T. den Dunnen, Liam J. Gretton, Raymond Dalgleish","doi":"10.1038/s41588-024-01938-w","DOIUrl":"10.1038/s41588-024-01938-w","url":null,"abstract":"Accurate naming of genetic variants is essential to identify clinical data that interpret the consequences of such variants. In partnership with the Human Genome Organization, we advocate for integration of VariantValidator in publishing of journals and databases, to improve the quality of shared genetic data and ultimately patient outcomes.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"56 11","pages":"2284-2286"},"PeriodicalIF":31.7,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
MHC Hammer reveals genetic and non-genetic HLA disruption in cancer evolution MHC Hammer 揭示了癌症进化过程中的遗传和非遗传 HLA 干扰
IF 31.7 1区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2024-10-02 DOI: 10.1038/s41588-024-01883-8
Clare Puttick, Thomas P. Jones, Michelle M. Leung, Felipe Galvez-Cancino, Jiali Liu, Manuel Varas-Godoy, Andrew Rowan, Oriol Pich, Carlos Martinez-Ruiz, Robert Bentham, Krijn K. Dijkstra, James R. M. Black, Rachel Rosenthal, Nnennaya Kanu, Kevin Litchfield, Roberto Salgado, David A. Moore, Peter Van Loo, Mariam Jamal-Hanjani, Sergio A. Quezada, TRACERx Consortium, Charles Swanton, Nicholas McGranahan
Disruption of the class I human leukocyte antigen (HLA) molecules has important implications for immune evasion and tumor evolution. We developed major histocompatibility complex loss of heterozygosity (LOH), allele-specific mutation and measurement of expression and repression (MHC Hammer). We identified extensive variability in HLA allelic expression and pervasive HLA alternative splicing in normal lung and breast tissue. In lung TRACERx and lung and breast TCGA cohorts, 61% of lung adenocarcinoma (LUAD), 76% of lung squamous cell carcinoma (LUSC) and 35% of estrogen receptor-positive (ER+) cancers harbored class I HLA transcriptional repression, while HLA tumor-enriched alternative splicing occurred in 31%, 11% and 15% of LUAD, LUSC and ER+ cancers. Consistent with the importance of HLA dysfunction in tumor evolution, in LUADs, HLA LOH was associated with metastasis and LUAD primary tumor regions seeding a metastasis had a lower effective neoantigen burden than non-seeding regions. These data highlight the extent and importance of HLA transcriptomic disruption, including repression and alternative splicing in cancer evolution. Major histocompatibility complex (MHC) loss of heterozygosity, allele-specific mutation and measurement of expression and repression (MHC Hammer) detects disruption to human leukocyte antigens due to mutations, loss of heterogeneity, altered gene expression or alternative splicing. Applied to lung and breast cancer datasets, the tool shows that these aberrations are common across cancer and can have clinical implications.
一类人类白细胞抗原(HLA)分子的破坏对免疫逃避和肿瘤进化有重要影响。我们开发了主要组织相容性复合体杂合性缺失(LOH)、等位基因特异性突变以及表达和抑制测量(MHC Hammer)。我们在正常肺部和乳腺组织中发现了 HLA 等位基因表达的广泛变异性和普遍存在的 HLA 替代剪接。在肺TRACERx和肺及乳腺TCGA队列中,61%的肺腺癌(LUAD)、76%的肺鳞癌(LUSC)和35%的雌激素受体阳性(ER+)癌症存在I类HLA转录抑制,而31%、11%和15%的LUAD、LUSC和ER+癌症存在HLA肿瘤丰富替代剪接。与HLA功能障碍在肿瘤演化中的重要性相一致的是,在LUAD中,HLA LOH与转移相关,而播种转移的LUAD原发肿瘤区域的有效新抗原负荷低于非播种区域。这些数据凸显了HLA转录组破坏的程度和重要性,包括抑制和替代剪接在癌症进化中的作用。
{"title":"MHC Hammer reveals genetic and non-genetic HLA disruption in cancer evolution","authors":"Clare Puttick, Thomas P. Jones, Michelle M. Leung, Felipe Galvez-Cancino, Jiali Liu, Manuel Varas-Godoy, Andrew Rowan, Oriol Pich, Carlos Martinez-Ruiz, Robert Bentham, Krijn K. Dijkstra, James R. M. Black, Rachel Rosenthal, Nnennaya Kanu, Kevin Litchfield, Roberto Salgado, David A. Moore, Peter Van Loo, Mariam Jamal-Hanjani, Sergio A. Quezada, TRACERx Consortium, Charles Swanton, Nicholas McGranahan","doi":"10.1038/s41588-024-01883-8","DOIUrl":"10.1038/s41588-024-01883-8","url":null,"abstract":"Disruption of the class I human leukocyte antigen (HLA) molecules has important implications for immune evasion and tumor evolution. We developed major histocompatibility complex loss of heterozygosity (LOH), allele-specific mutation and measurement of expression and repression (MHC Hammer). We identified extensive variability in HLA allelic expression and pervasive HLA alternative splicing in normal lung and breast tissue. In lung TRACERx and lung and breast TCGA cohorts, 61% of lung adenocarcinoma (LUAD), 76% of lung squamous cell carcinoma (LUSC) and 35% of estrogen receptor-positive (ER+) cancers harbored class I HLA transcriptional repression, while HLA tumor-enriched alternative splicing occurred in 31%, 11% and 15% of LUAD, LUSC and ER+ cancers. Consistent with the importance of HLA dysfunction in tumor evolution, in LUADs, HLA LOH was associated with metastasis and LUAD primary tumor regions seeding a metastasis had a lower effective neoantigen burden than non-seeding regions. These data highlight the extent and importance of HLA transcriptomic disruption, including repression and alternative splicing in cancer evolution. Major histocompatibility complex (MHC) loss of heterozygosity, allele-specific mutation and measurement of expression and repression (MHC Hammer) detects disruption to human leukocyte antigens due to mutations, loss of heterogeneity, altered gene expression or alternative splicing. Applied to lung and breast cancer datasets, the tool shows that these aberrations are common across cancer and can have clinical implications.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"56 10","pages":"2121-2131"},"PeriodicalIF":31.7,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41588-024-01883-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Heterogeneous genetic architectures of prostate cancer susceptibility in sub-Saharan Africa 撒哈拉以南非洲地区前列腺癌易感性的异质遗传结构
IF 31.7 1区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2024-10-02 DOI: 10.1038/s41588-024-01931-3
Rohini Janivara, Wenlong C. Chen, Ujani Hazra, Shakuntala Baichoo, Ilir Agalliu, Paidamoyo Kachambwa, Corrine N. Simonti, Lyda M. Brown, Saanika P. Tambe, Michelle S. Kim, Maxine Harlemon, Mohamed Jalloh, Dillon Muzondiwa, Daphne Naidoo, Olabode O. Ajayi, Nana Yaa Snyper, Lamine Niang, Halimatou Diop, Medina Ndoye, James E. Mensah, Afua O. D. Abrahams, Richard Biritwum, Andrew A. Adjei, Akindele O. Adebiyi, Olayiwola Shittu, Olufemi Ogunbiyi, Sikiru Adebayo, Maxwell M. Nwegbu, Hafees O. Ajibola, Olabode P. Oluwole, Mustapha A. Jamda, Audrey Pentz, Christopher A. Haiman, Petrus V. Spies, André van der Merwe, Michael B. Cook, Stephen J. Chanock, Sonja I. Berndt, Stephen Watya, Alexander Lubwama, Mazvita Muchengeti, Sean Doherty, Natalie Smyth, David Lounsbury, Brian Fortier, Thomas E. Rohan, Judith S. Jacobson, Alfred I. Neugut, Ann W. Hsing, Alexander Gusev, Oseremen I. Aisuodionoe-Shadrach, Maureen Joffe, Ben Adusei, Serigne M. Gueye, Pedro W. Fernandez, Jo McBride, Caroline Andrews, Lindsay N. Petersen, Joseph Lachance, Timothy R. Rebbeck
Men of African descent have the highest prostate cancer incidence and mortality rates, yet the genetic basis of prostate cancer in African men has been understudied. We used genomic data from 3,963 cases and 3,509 controls from Ghana, Nigeria, Senegal, South Africa and Uganda to infer ancestry-specific genetic architectures and fine-map disease associations. Fifteen independent associations at 8q24.21, 6q22.1 and 11q13.3 reached genome-wide significance, including four new associations. Intriguingly, multiple lead associations are private alleles, a pattern arising from recent mutations and the out-of-Africa bottleneck. These African-specific alleles contribute to haplotypes with odds ratios above 2.4. We found that the genetic architecture of prostate cancer differs across Africa, with effect size differences contributing more to this heterogeneity than allele frequency differences. Population genetic analyses reveal that African prostate cancer associations are largely governed by neutral evolution. Collectively, our findings emphasize the utility of conducting genetic studies that use diverse populations. Genome-wide association analyses of prostate cancer in men from sub-Saharan Africa identify population-specific risk variants and regional differences in effect sizes. Founder effects contribute to continental differences in the genetic architecture of prostate cancer.
非洲裔男性的前列腺癌发病率和死亡率都是最高的,但对非洲男性前列腺癌的遗传基础却研究不足。我们利用来自加纳、尼日利亚、塞内加尔、南非和乌干达的 3,963 例病例和 3,509 例对照的基因组数据,推断了特定祖先的基因结构,并绘制了疾病相关的精细图谱。8q24.21、6q22.1和11q13.3的15个独立关联达到了全基因组意义,其中包括4个新关联。耐人寻味的是,多个主要关联是私有等位基因,这种模式产生于最近的突变和非洲以外的瓶颈。这些非洲特异性等位基因导致单倍型的几率比超过 2.4。我们发现,前列腺癌的遗传结构在非洲各地有所不同,效应大小差异比等位基因频率差异对这种异质性的影响更大。人群遗传分析表明,非洲前列腺癌的关联在很大程度上受中性进化的影响。总之,我们的研究结果强调了利用不同人群进行遗传研究的实用性。
{"title":"Heterogeneous genetic architectures of prostate cancer susceptibility in sub-Saharan Africa","authors":"Rohini Janivara, Wenlong C. Chen, Ujani Hazra, Shakuntala Baichoo, Ilir Agalliu, Paidamoyo Kachambwa, Corrine N. Simonti, Lyda M. Brown, Saanika P. Tambe, Michelle S. Kim, Maxine Harlemon, Mohamed Jalloh, Dillon Muzondiwa, Daphne Naidoo, Olabode O. Ajayi, Nana Yaa Snyper, Lamine Niang, Halimatou Diop, Medina Ndoye, James E. Mensah, Afua O. D. Abrahams, Richard Biritwum, Andrew A. Adjei, Akindele O. Adebiyi, Olayiwola Shittu, Olufemi Ogunbiyi, Sikiru Adebayo, Maxwell M. Nwegbu, Hafees O. Ajibola, Olabode P. Oluwole, Mustapha A. Jamda, Audrey Pentz, Christopher A. Haiman, Petrus V. Spies, André van der Merwe, Michael B. Cook, Stephen J. Chanock, Sonja I. Berndt, Stephen Watya, Alexander Lubwama, Mazvita Muchengeti, Sean Doherty, Natalie Smyth, David Lounsbury, Brian Fortier, Thomas E. Rohan, Judith S. Jacobson, Alfred I. Neugut, Ann W. Hsing, Alexander Gusev, Oseremen I. Aisuodionoe-Shadrach, Maureen Joffe, Ben Adusei, Serigne M. Gueye, Pedro W. Fernandez, Jo McBride, Caroline Andrews, Lindsay N. Petersen, Joseph Lachance, Timothy R. Rebbeck","doi":"10.1038/s41588-024-01931-3","DOIUrl":"10.1038/s41588-024-01931-3","url":null,"abstract":"Men of African descent have the highest prostate cancer incidence and mortality rates, yet the genetic basis of prostate cancer in African men has been understudied. We used genomic data from 3,963 cases and 3,509 controls from Ghana, Nigeria, Senegal, South Africa and Uganda to infer ancestry-specific genetic architectures and fine-map disease associations. Fifteen independent associations at 8q24.21, 6q22.1 and 11q13.3 reached genome-wide significance, including four new associations. Intriguingly, multiple lead associations are private alleles, a pattern arising from recent mutations and the out-of-Africa bottleneck. These African-specific alleles contribute to haplotypes with odds ratios above 2.4. We found that the genetic architecture of prostate cancer differs across Africa, with effect size differences contributing more to this heterogeneity than allele frequency differences. Population genetic analyses reveal that African prostate cancer associations are largely governed by neutral evolution. Collectively, our findings emphasize the utility of conducting genetic studies that use diverse populations. Genome-wide association analyses of prostate cancer in men from sub-Saharan Africa identify population-specific risk variants and regional differences in effect sizes. Founder effects contribute to continental differences in the genetic architecture of prostate cancer.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"56 10","pages":"2093-2103"},"PeriodicalIF":31.7,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Aneuploidy as a driver of human cancer 非整倍体是人类癌症的驱动因素
IF 31.7 1区 生物学 Q1 GENETICS & HEREDITY Pub Date : 2024-10-02 DOI: 10.1038/s41588-024-01916-2
Eran Sdeor, Hajime Okada, Ron Saad, Tal Ben-Yishay, Uri Ben-David
Aneuploidy, an abnormal chromosome composition, is a major contributor to cancer development and progression and an important determinant of cancer therapeutic responses and clinical outcomes. Despite being recognized as a hallmark of human cancer, the exact role of aneuploidy as a ‘driver’ of cancer is still largely unknown. Identifying the specific genetic elements that underlie the recurrence of common aneuploidies remains a major challenge of cancer genetics. In this Review, we discuss recurrent aneuploidies and their function as drivers of tumor development. We then delve into the context-dependent identification and functional characterization of the driver genes underlying driver aneuploidies and examine emerging strategies to uncover these driver genes using cancer genomics data and cancer models. Lastly, we explore opportunities for targeting driver aneuploidies in cancer by leveraging the functional consequences of these common genetic alterations. This Review discusses recurrent aneuploidies driving human cancer, methods to identify them and strategies to uncover underlying driver genes. It highlights genomic and experimental approaches to study and ultimately target driver aneuploidies.
非整倍体(染色体组成异常)是癌症发生和发展的主要因素,也是癌症治疗反应和临床结果的重要决定因素。尽管非整倍体被认为是人类癌症的标志,但其作为癌症 "驱动因素 "的确切作用在很大程度上仍不为人所知。确定导致常见非整倍体复发的特定遗传因素仍是癌症遗传学的一大挑战。在本综述中,我们将讨论复发性非整倍体及其作为肿瘤发生驱动因素的功能。然后,我们深入探讨了驱动非整倍体的驱动基因的识别和功能特征,并研究了利用癌症基因组学数据和癌症模型发现这些驱动基因的新策略。最后,我们探讨了利用这些常见基因改变的功能性后果来靶向治疗癌症驱动非整倍体的机会。
{"title":"Aneuploidy as a driver of human cancer","authors":"Eran Sdeor, Hajime Okada, Ron Saad, Tal Ben-Yishay, Uri Ben-David","doi":"10.1038/s41588-024-01916-2","DOIUrl":"10.1038/s41588-024-01916-2","url":null,"abstract":"Aneuploidy, an abnormal chromosome composition, is a major contributor to cancer development and progression and an important determinant of cancer therapeutic responses and clinical outcomes. Despite being recognized as a hallmark of human cancer, the exact role of aneuploidy as a ‘driver’ of cancer is still largely unknown. Identifying the specific genetic elements that underlie the recurrence of common aneuploidies remains a major challenge of cancer genetics. In this Review, we discuss recurrent aneuploidies and their function as drivers of tumor development. We then delve into the context-dependent identification and functional characterization of the driver genes underlying driver aneuploidies and examine emerging strategies to uncover these driver genes using cancer genomics data and cancer models. Lastly, we explore opportunities for targeting driver aneuploidies in cancer by leveraging the functional consequences of these common genetic alterations. This Review discusses recurrent aneuploidies driving human cancer, methods to identify them and strategies to uncover underlying driver genes. It highlights genomic and experimental approaches to study and ultimately target driver aneuploidies.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"56 10","pages":"2014-2026"},"PeriodicalIF":31.7,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
期刊
Nature genetics
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1