Tooth development and disease

Welcome!

Thank you for visiting our site profiling our work on the developing tooth! This work includes ChIP-seq data we generated for the E13.5 incisor (GSE197645), single cell transcriptomic data from  GSE142201 , bulk transcriptomic data from SRP308455, and GWAS data from the GWAS catalog. Detailed scripts for this project can be found at our github page.

This project also included the functional annotation (18 state chromatin segmentation) of all ENCODE mouse ChIP-seq datasets (performed by Alexis Hardy), which are available here.

To further explore our single cell transcriptomics analyses, please check out our Shiny Server! This allows you to explore expression of your favorite genes, scores of our custom modules, gene ontology classifications, cluster makeup percentages, and more.

Please check out our preprint of all analysis on biorxiv.

Please check out our preprint of our detailed work on the single cell transcriptomics data on biorxiv.

Integration of Multimodal Data To Prioritize Candidate Dental Disease Genes

By integrating the datasets mentioned above and outlined in detail in the following sections, we generated a prioritized gene list which can be explored in the following dropdown menu.

We validated AGAP1, a high-priority novel candidate gene which had previously been assayed as a loss of function whole-body knockout by the Knockout Mouse Project.

Exploration of Prioritized Dental Disease Genes

AGAP1 is a likely dental disease gene

AGAP1 is a likely dental disease gene

Conserved Craniofacial Enhancers Contribute to Dental Development and Disease Risk

Conserved Craniofacial Enhancers Contribute to Dental Development and Disease Risk

A. Scatterplot of GREGOR (genomic regulatory elements and Gwas overlap algoRithm) analysis of enrichment of “Odontogenesis” -associated SNPs from GWAS Catalog in active enhancers annotated by 18 state chromatin segmentations genome-wide for samples from Wilderman et al 2018 (orange circles), Roadmap Epigenome (grey circles), and our own 18 state segmentations from Mouse ENCODE craniofacial (orange triangles) and other mouse tissue samples (grey triangles). B. GREGOR analysis of “Caries”-associated SNPs from GWAS Catalog as in A. C. Visualization of the locus surrounding rs12229918 (chr5:134509987, hg19) and nearby fine-mapped variants associated with decreased tooth number and delayed tooth eruption by [54]. Mouse craniofacial 18 state segmentations were generated as described in Methods from publicly available data from ENCODE [60]. Human craniofacial 18 state segmentation and composite H3K27ac, H3K4me2, and H3K4me3 p-value signal tracks were obtained from [37]. In situ hybridization images of Wif1 and HMGB2 were obtained from GenePaint [62]. Enhancer assay images were obtained from VISTA [63].

Hg19 Conserved Tooth Enhancer Explorer

Please find here an interactive UCSC genome browser session (hg19) of our human craniofacial 18 state chromatin segmentation tracks alongside our novel E13.5 mouse incisor enhancer calls.

Mm10 Conserved Tooth Enhancer Explorer

Please find here an interactive UCSC genome browser session (mm10) of our 18 state chromatin segmentation tracks of all mouse ENCODE alongside our novel E13.5 mouse incisor enhancer calls.

Exploration of VISTA-Validated Tooth Specific Enhancers

Single Cell Transcriptomics Identifies the Putative Enamel Knot

Single Cell Transcriptomics Identifies the Putative Enamel Knot

Single Cell Transcriptomics Identifies the Putative Enamel Knot

Single Cell Transcriptomics Identifies the Putative Enamel Knot

Exploration of the Putative Enamel Knot Transcriptomic Signature