Window of Susceptibility for Zika-Induced Microcephaly Identified by Temporal Gene Analysis

Abstract

Increased understanding of developmental disorders of the brain has shown that genetic mutations, environmental toxins and biological insults typically act during developmental windows of susceptibility. Through analysis of developmental time-course gene expression data derived from human pluripotent stem cells, with disease association, pathway, and protein interaction databases, we identify windows of developmental time that appear most vulnerable to a specific insult, and therefore, the time periods for productive interventions. The results are displayed as interactive Susceptibility Windows Ontological Transcriptome (SWOT) Clocks illustrating disease susceptibility over developmental time. Using this method, we determine the likely windows of susceptibility for multiple neurological disorders, including Zika-induced microcephaly. We find that genes impacted by Zika infection are most active in the earliest stages of neural development, prior to cerebral cortex layer formation.