Open AccessiPhemap: an atlas of phenotype to genotype relationships of human iPSC models of neurological diseases
Author(s) -
Hollingsworth Ethan W,
Vaughn Jacob E,
Orack Josh C,
Skinner Chelsea,
Khouri Jamil,
Lizarraga Sofia B,
Hester Mark E,
Watanabe Fumihiro,
Kosik Kenneth S,
Imitola Jaime
Publication year - 2017
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201708191
Subject(s) - neuroimmunology , neurogenetics , neuroscience , neuroeconomics , neural stem cell , library science , neurology , gerontology , psychology , medicine , biology , stem cell , computer science , genetics , disease , central nervous system
Abstract Disease modeling with induced pluripotent stem cells (i PSC s) 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 i PS 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 i PSC ‐derived models while our web tool provides a platform for researchers to query and deposit phenotypic information of neurological diseases.