5/5: This work was made possible by an incredible team including Dr. Fregoso, Manith Atapattu, LuLu Callies, Deja Monet, Amy Leonardson, Lindsay Clark, and Stella Xu. With support from the Hydrocephalus Association and NIH training awards. #NeurodevelopmentalDisorders #SeattleChildrens

4/5: Loss of miR-9-2 causes widespread disruption of gene networks in vascular, choroid plexus, and neuronal cell types of the developing mouse brain. This suggests MIR-9-2 may play an equally important role in human brain development and in the etiology of neurodevelopmental disorders. #SingleCell

3/5: A role for MIR-9-2 in this disorder has been underappreciated because it was thought to be redundant. We show loss of even just one copy of miR-9-2 causes early hemorrhages, enlarged ventricles, and disrupted development in the mouse brain, mirroring features of 5q14.3 Microdeletion Syndrome.

2/5: The microRNA MIR-9-2 is often deleted along with other genes in human 5q14.3 Microdeletion Syndrome, a rare but severe neurodevelopmental disorder with developmental delay, disrupted speech, epilepsy, and frequently with disrupted blood vessels and enlarged brain ventricles.

5/5: This work was made possible by an incredible team including Dr. Fregoso, Manith Atapattu, LuLu Callies, Deja Monet, Amy Leonardson, Lindsay Clark, and Stella Xu. With support from the Hydrocephalus Association and NIH training awards. #NeurodevelopmentalDisorders #SeattleChildrens

4/5: Loss of miR-9-2 causes widespread disruption of gene networks in vascular, choroid plexus, and neuronal cell types of the developing mouse brain. This suggests MIR-9-2 may play an equally important role in human brain development and in the etiology of neurodevelopmental disorders. #SingleCell

3/5: A role for MIR-9-2 in this disorder has been underappreciated because it was thought to be redundant. We show loss of even just one copy of miR-9-2 causes early hemorrhages, enlarged ventricles, and disrupted development in the mouse brain, mirroring features of 5q14.3 Microdeletion Syndrome.

2/5: The microRNA MIR-9-2 is often deleted along with other genes in human 5q14.3 Microdeletion Syndrome, a rare but severe neurodevelopmental disorder with developmental delay, disrupted speech, epilepsy, and frequently with disrupted blood vessels and enlarged brain ventricles.

I feel compelled to say that this powerful resource that Leah has provided for our field would not have been possible without the High Performance Computing cluster at Seattle Children's supported in part by....Indirect Costs!

I couldn't be more proud of Leah and the contributions that she made to retinal disease variant interpretation while in our lab! Congratulations Leah on your new adventures as a Research Scientist III in the Pavel-Dinu Lab at Seattle Children's!

Take home points:
1) Interpretable models trained on scATAC are accurate and cell-class-specific.
2) Models identify emergent features of enhancers such as putative TF binding motifs.
3) Variant Impact Prediction scores allow quick prioritization of retinal disease associated regulatory variants.

Leah's excellent manuscript describing these analyses is now live: www.biorxiv.org/content/10.1....