iPhemap: an atlas of phenotype to genotype relationships of human iPSC models of neurological diseases.
iPhemap: an atlas of phenotype to genotype relationships of human iPSC models of neurological diseases.
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DOI：
10.15252/emmm.201708191
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发表时间：
2017-12
影响因子：
11.1
通讯作者：
Imitola J
中科院分区：
文献类型：
--
作者：
Hollingsworth EW;Vaughn JE;Orack JC;Skinner C;Khouri J;Lizarraga SB;Hester ME;Watanabe F;Kosik KS;Imitola J
使用诱导多能干细胞（iPSC）的疾病建模正在创造大量的表型信息，这些信息已经变得难以遵循和解释。在这里，我们报告了93篇已发表文章中神经系统疾病模型的研究实践和报告偏倚的系统分析。我们发现目前的研究实践中存在异质性，并且对某些疾病存在报告偏倚。此外，我们从243名患者和214名对照中鉴定了663种中枢神经系统细胞来源的表型，这些表型因体外突变类型和发育阶段而异。我们将这些表型聚类到一个分类系统中，并描述这些表型-基因型关系，以生成一个表型遗传图谱，揭示以前不相关基因之间的新相关性。我们还发现，与细胞表型相关的患者来源的分子谱的改变，以及失调的基因在具有病理学的脑区域中显示出主要表达。最后，我们开发了iPS细胞表型遗传图谱项目图谱（iPhemap），这是一个开放的在线数据库，用于不断对疾病表型进行分类。总的来说，我们的研究结果为iPSC衍生模型的表型遗传学提供了新的见解，而我们的网络工具为研究人员提供了一个查询和存款神经系统疾病表型信息的平台。
Disease modeling with induced pluripotent stem cells (iPSCs) is creating an abundance of phenotypic information that has become difficult to follow and interpret. Here, we report a systematic analysis of research practices and reporting bias in neurological disease models from 93 published articles. We find heterogeneity in current research practices and a reporting bias toward certain diseases. Moreover, we identified 663 CNS cell‐derived phenotypes from 243 patients and 214 controls, which varied by mutation type and developmental stage in vitro. We clustered these phenotypes into a taxonomy and characterized these phenotype–genotype relationships to generate a phenogenetic map that revealed novel correlations among previously unrelated genes. We also find that alterations in patient‐derived molecular profiles associated with cellular phenotypes, and dysregulated genes show predominant expression in brain regions with pathology. Last, we developed the iPS cell phenogenetic map project atlas (iPhemap), an open submission, online database to continually catalog disease phenotypes. Overall, our findings offer new insights into the phenogenetics of iPSC‐derived models while our web tool provides a platform for researchers to query and deposit phenotypic information of neurological diseases.