iPhemap: an atlas of phenotype to genotype relationships of human iPSC models of neurological diseases

EMBO Mol Med. 2017 Dec;9(12):1742-1762. doi: 10.15252/emmm.201708191.


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.

Keywords: Alzheimer's disease; iPSCs; neurogenetics; neurological diseases; phenogenetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation
  • Cluster Analysis
  • Databases, Factual
  • Genetic Association Studies
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / metabolism*
  • Meta-Analysis as Topic
  • Models, Biological
  • Nervous System Diseases / genetics
  • Nervous System Diseases / pathology*
  • Transcriptome
  • User-Computer Interface*