Pub Date : 2023-11-17DOI: 10.1101/2023.08.02.551517
Ian Hoskins, Shilpa Rao, Charisma Tante, Can Cenik
Multiplexed assays of variant effect are powerful methods to profile the consequences of rare variants on gene expression and organismal fitness. Yet, few studies have integrated several multiplexed assays to map variant effects on gene expression in coding sequences. Here, we pioneered a multiplexed assay based on polysome profiling to measure variant effects on translation at scale, uncovering single-nucleotide variants that increase and decrease ribosome load. By combining high-throughput ribosome load data with multiplexed mRNA and protein abundance readouts, we mapped the cis-regulatory landscape of thousands of catechol-O-methyltransferase (COMT) variants from RNA to protein and found numerous coding variants that alter COMT expression. Finally, we trained machine learning models to map signatures of variant effects on COMT gene expression and uncovered both directional and divergent impacts across expression layers. Our analyses reveal expression phenotypes for thousands of variants in COMT and highlight variant effects on both single and multiple layers of expression. Our findings prompt future studies that integrate several multiplexed assays for the readout of gene expression.
变异效应的多重分析是分析罕见变异对基因表达和机体适应性影响的有力方法。然而，很少有研究整合了几种多重分析来绘制编码序列中基因表达的变异效应。在这里，我们开创了一种基于多聚体分析的多重分析方法，以大规模测量变异对翻译的影响，揭示单核苷酸变异增加和减少核糖体负荷。通过将高通量核糖体负载数据与多路mRNA和蛋白质丰度读数相结合，我们绘制了数千种儿茶酚- o -甲基转移酶(COMT)从RNA到蛋白质的顺式调控图景，并发现了许多改变COMT表达的编码变体。最后，我们训练了机器学习模型来绘制COMT基因表达变异效应的特征，并揭示了跨表达层的方向性和发散性影响。我们的分析揭示了COMT中数千种变异的表达表型，并强调了变异对单层和多层表达的影响。我们的发现促进了未来的研究，整合了几种多重检测来读取基因表达。
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{"title":"The wolf.","authors":"R. K. Greenbank","doi":"10.2307/j.ctt1j5dfrf.17","DOIUrl":"https://doi.org/10.2307/j.ctt1j5dfrf.17","url":null,"abstract":"","PeriodicalId":14793,"journal":{"name":"Journal of abnormal psychology","volume":"54 3 1","pages":"417-9"},"PeriodicalIF":4.6,"publicationDate":"2023-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49167355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Supplemental Material for Self-Esteem and Psychosis in Daily Life: An Experience Sampling Study","authors":"","doi":"10.1037/abn0000722.supp","DOIUrl":"https://doi.org/10.1037/abn0000722.supp","url":null,"abstract":"","PeriodicalId":14793,"journal":{"name":"Journal of abnormal psychology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2021-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49042133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Supplemental Material for Longitudinal Group and Individual Networks of Eating Disorder Symptoms in Individuals Diagnosed With an Eating Disorder","authors":"","doi":"10.1037/abn0000727.supp","DOIUrl":"https://doi.org/10.1037/abn0000727.supp","url":null,"abstract":"","PeriodicalId":14793,"journal":{"name":"Journal of abnormal psychology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2021-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48930747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Supplemental Material for The Impact of Punishment on Cognitive Control in a Clinical Population Characterized by Heightened Punishment Sensitivity","authors":"","doi":"10.1037/abn0000713.supp","DOIUrl":"https://doi.org/10.1037/abn0000713.supp","url":null,"abstract":"","PeriodicalId":14793,"journal":{"name":"Journal of abnormal psychology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2021-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47215569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Supplemental Material for Multimethod Assessment of Pubertal Timing and Associations With Internalizing Psychopathology in Early Adolescent Girls","authors":"","doi":"10.1037/abn0000721.supp","DOIUrl":"https://doi.org/10.1037/abn0000721.supp","url":null,"abstract":"","PeriodicalId":14793,"journal":{"name":"Journal of abnormal psychology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2021-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43376121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Supplemental Material for Analyzing Dynamic Change in Children’s Socioemotional Development Using the Strengths and Difficulties Questionnaire in a Large United Kingdom Longitudinal Study","authors":"","doi":"10.1037/abn0000714.supp","DOIUrl":"https://doi.org/10.1037/abn0000714.supp","url":null,"abstract":"","PeriodicalId":14793,"journal":{"name":"Journal of abnormal psychology","volume":"236 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2021-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"57651610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Supplemental Material for Estimating the Symptom Structure of Bipolar Disorder via Network Analysis: Energy Dysregulation as a Central Symptom","authors":"","doi":"10.1037/abn0000715.supp","DOIUrl":"https://doi.org/10.1037/abn0000715.supp","url":null,"abstract":"","PeriodicalId":14793,"journal":{"name":"Journal of abnormal psychology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2021-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41621042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Supplemental Material for All by Myself: Loneliness in Social Anxiety Disorder","authors":"","doi":"10.1037/abn0000705.supp","DOIUrl":"https://doi.org/10.1037/abn0000705.supp","url":null,"abstract":"","PeriodicalId":14793,"journal":{"name":"Journal of abnormal psychology","volume":"1 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2021-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41501925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adela-Maria Isvoranu, Sacha Epskamp, Mike W-L Cheung
Posttraumatic stress disorder (PTSD) researchers have increasingly used psychological network models to investigate PTSD symptom interactions, as well as to identify central driver symptoms. It is unclear, however, how generalizable such results are. We have developed a meta-analytic framework for aggregating network studies while taking between-study heterogeneity into account and applied this framework in the first-ever meta-analytic study of PTSD symptom networks. We analyzed the correlational structures of 52 different samples with a total sample size of n = 29,561 and estimated a single pooled network model underlying the data sets, investigated the scope of between-study heterogeneity, and assessed the performance of network models estimated from single studies. Our main findings are that: (a) We identified large between-study heterogeneity, indicating that it should be expected for networks of single studies to not perfectly align with one-another, and meta-analytic approaches are vital for the study of PTSD networks. (b) While several clear symptom-links, interpretable clusters, and significant differences between strength of edges and centrality of nodes can be identified in the network, no single or small set of nodes that clearly played a more central role than other nodes could be pinpointed, except for the symptom "amnesia" that was clearly the least central symptom. (c) Despite large between-study heterogeneity, we found that network models estimated from single samples can lead to similar network structures as the pooled network model. We discuss the implications of these findings for both the PTSD literature as well as methodological literature on network psychometrics. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
创伤后应激障碍(PTSD)研究人员越来越多地使用心理网络模型来研究PTSD症状的相互作用，以及识别中心驱动症状。然而，目前尚不清楚这些结果有多普遍。我们开发了一个综合网络研究的元分析框架，同时考虑了研究间的异质性，并将该框架应用于首次PTSD症状网络的元分析研究。我们分析了52个不同样本的相关结构，总样本量为n = 29,561，并估计了数据集背后的单一汇集网络模型，调查了研究间异质性的范围，并评估了从单个研究中估计的网络模型的性能。我们的主要发现是:(a)我们发现了很大的研究间异质性，这表明单个研究的网络之间并不完全一致，元分析方法对于PTSD网络的研究至关重要。(b)虽然可以在网络中识别出几个明确的症状链接、可解释的集群以及边缘强度和节点中心性之间的显著差异，但除了“失忆”症状显然是最不重要的症状外，没有一个或一小组节点明显比其他节点发挥更重要的作用。(c)尽管研究之间存在很大的异质性，但我们发现，从单个样本估计的网络模型可以导致与池化网络模型相似的网络结构。我们将讨论这些发现对PTSD文献以及网络心理测量学方法学文献的影响。(PsycInfo Database Record (c) 2021 APA，版权所有)。
{"title":"Network models of posttraumatic stress disorder: A meta-analysis.","authors":"Adela-Maria Isvoranu, Sacha Epskamp, Mike W-L Cheung","doi":"10.1037/abn0000704","DOIUrl":"https://doi.org/10.1037/abn0000704","url":null,"abstract":"<p><p>Posttraumatic stress disorder (PTSD) researchers have increasingly used psychological network models to investigate PTSD symptom interactions, as well as to identify central driver symptoms. It is unclear, however, how generalizable such results are. We have developed a meta-analytic framework for aggregating network studies while taking between-study heterogeneity into account and applied this framework in the first-ever meta-analytic study of PTSD symptom networks. We analyzed the correlational structures of 52 different samples with a total sample size of n = 29,561 and estimated a single pooled network model underlying the data sets, investigated the scope of between-study heterogeneity, and assessed the performance of network models estimated from single studies. Our main findings are that: (a) We identified large between-study heterogeneity, indicating that it should be expected for networks of single studies to not perfectly align with one-another, and meta-analytic approaches are vital for the study of PTSD networks. (b) While several clear symptom-links, interpretable clusters, and significant differences between strength of edges and centrality of nodes can be identified in the network, no single or small set of nodes that clearly played a more central role than other nodes could be pinpointed, except for the symptom \"amnesia\" that was clearly the least central symptom. (c) Despite large between-study heterogeneity, we found that network models estimated from single samples can lead to similar network structures as the pooled network model. We discuss the implications of these findings for both the PTSD literature as well as methodological literature on network psychometrics. (PsycInfo Database Record (c) 2021 APA, all rights reserved).</p>","PeriodicalId":14793,"journal":{"name":"Journal of abnormal psychology","volume":"130 8","pages":"841-861"},"PeriodicalIF":4.6,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39676558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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