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Transcriptomic atlas regulators of human organogenesis and causes of human congenital disorders

Principal components analysis (PCA) See also Nature - An atlas of embryogenesis

LgPCA points to master regulators of human organogenesis and the causes of human congenital disorders.

(a) Predicted regulation by iRegulon (Janky et al., 2014) of the most extreme 1000 genes for different PCs identifies known and unexpected transcription factors regulating human organogenesis. In several examples, individual transcription factors (e.g. REST, NR5A1, HNF4A, FOXA1 and SRF) were predicted to regulate nearly half of the most extreme 1000 genes.

(b) Transcription factors at the extremes of individual PCs in the LgPCA are responsible for a diverse range of congenital disorders (red names in the ovals for heart and testis). To validate the utility of these data, we conservatively selected some of the earliest critical regions for these disorders (two ‘Proven’ examples on the left; all 53 listed in Supplementary file 1H). LgPCA frequently isolated the correct transcription factor from an average of 111 genes across >10 Mb, shown for NKX2-5 in congenital heart disease and SOX9 in campomelic dysplasia. Beyond this validation LgPCA similarly predicts causative transcription factors (blue) for many unresolved congenital disorders such as developmental heart abnormalities in Chr1p36 deletion syndrome and sex reversal / disorders of sex differentiation (DSD) (all 13 examples in Supplementary file 1H).

Reference

<pubmed>27557446</pubmed>

elife

Copyright

© 2016, Gerrard et al This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

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