FaceBase Resources for Fetal Alcohol Spectrum Disorders Researchers Steve Scholnick, Ph.D. NIDCR/NIH

What is FaceBase? Both a consortium working collaboratively on craniofacial development/birth defects and a website (www.facebase.org) for disseminating those data to the wider research community Current focus is on the midface and clefting Goal is to be a community resource, generating and disseminating large datasets that might be difficult or inefficient for individual labs to generate on their own developmental stage-specific gene expression profiles, genome-wide genotypes, etc. tools to search or analyze these data frees those individual labs from having to generate the data themselves and allows them to more easily generate novel hypotheses

FaceBase organization Coordinating hub Murray/Marazita (U Iowa, U Pittsburgh) Clouthier, Artinger, Postlethwait (U Colorado, U Oregon) miRNAs (zebrafish mouse) Beaty (Hopkins) CNVs/GWAS confirmation (human) Shapiro (U Washington) Shape-based image retrieval (human) Weinberg, Marazita (U Pittsburgh) 3D Facial Norms database (human) Spritz (U Colorado) Genome-wide QTL Morphometry (mouse & human) Donahue, S. Murray (Jackson Lab) New conditional clefting models (mouse) Visel (LBNL) ChIP-seq screen for craniofacial enhancers (mouse) Chai (USC) Mutant models/microCT/MRI (mouse) Potter (CCHMC) Gene expression atlas (mouse) Fraser (Caltech/USC) Developmental atlases (MRI, optical, in situ) (quail & mouse) Steering Committee (project PIs) NIDCR program Scientific Leadership Group Animal models Humans Both tools data

FaceBase spoke projects – data types Project name Data types Oral Clefts: Moving from Genome Wide Studies Toward Functional Genomics Genome-wide CNV scan, DNA sequence data Research On Functional Genomics, Image Analysis And Rescue Of Cleft Palate Mouse microCT, gene expression data Identification of miRNAs involved midfacial development and clefting miRNA microarray and RNA-seq data Genetic Tools and Resources for Orofacial Clefting Research Novel Cre-driver lines Functional analysis of neural crest & palate: Imaging craniofacial development microMRI, lightsheet microscopy, ISH 3D Analysis of Facial Variation: Data Repository and Genetics 3D normative facial shape database & GWAS Global Gene Expression Atlas of Craniofacial Development Microarray & RNA-seq data across development Shape-Based Retrieval of 3D Craniofacial Data Software for image analysis/retrieval & ontology Genetic Determinants of Orofacial Shape and Relationship to Cleft Lip/Palate GWAS of normal facial shape in children Genome-Wide Atlas of Craniofacial Transcriptional Enhancers ChIP-seq enhancer screen & RNA-seq data

Data display/presentation

Data available – browse or search

Data available – an example

Available data formats A good deal of what’s available on FaceBase consists of global gene expression data . Depending on the project, data may be available as Excel spreadsheets .cel files That’s great if you’re experienced in global analyses of gene expression and want the raw data But what about the rest of us?

Custom version of UCSC genome browser Craniofacial tracks: enhancer elements, expression data… Enhancers and gene expression near mouse Irf6 gene

Custom version of UCSC genome browser Craniofacial tracks: enhancer elements, expression data… CNVs near human chromosome 7 Hox gene cluster

Resource & Tool creation

FaceBase mouse repository PIs: Leah Rae Donahue and Steve Murray at Jackson Lab A community resource for distributing FaceBase generated strains and useful strains donated by the wider community maintained at Jackson Labs http://www.jax.org/facebase/index.html http://jaxmice.jax.org/list/fbmodels.html https://www.facebase.org/resources/jax-strains many mouse lines Cre driver strains mutant models

FaceBase mouse repository Users can follow the progress towards strains of interest on the FaceBase site

FaceBase biorepository –human specimens Run by Jeff Murray’s group at U of Iowa Cases and related controls 26 different syndromes plus nonsyndromic cases (samples from 590 individuals as of 10/2012) DNA samples, family histories, environmental exposure records, etc.

Other FaceBase resources Developmental atlases FishFace (from Chuck Kimmel’s lab), https://www.facebase.org/fishface/home Ontology of Craniofacial Development and Malformation (OCDM) https://www.facebase.org/content/ocdm Gene Wiki

Of particular interest to FASD researcherS…

3D Facial Norms Database PIs: Seth Weinberg & Mary Marazita, U of Pittsburgh Goal is to obtain morphometry from males and females 3 - 40 years of age (cross-sectional study design) all normal individuals without family history of craniofacial dysmorphology All U.S. Caucasians Recruiting goal of ~3500 individuals. ~1500 recruited as of August, 2012 quantitative morphometric data obtained from facial surface images taken obtained by 3dMD camera system (some caliper measurements as well) saliva also collected for DNA to be used in future genetic analysis of variation in normal facial shape Summary data from a subset of subjects are now available online and individual level data can be requested also available: detailed protocols, pre-computed analyses, Z-score calculator tool for comparison of individual data to norms

3D Facial Norms Database entry page

3D Facial Norms Database summary stats

3D Facial Norms Database summary stats

3D Facial Norms Database search

3D Facial Norms Database results

3D Facial Norms Database Z-score Z-score calculator for comparing data from an individual to the database Both Caliper Facial Measurements and 3D Facial Measurements available

PI: Rich Spritz, U of Colorado, Denver Genetic Determinants of Orofacial Shape and Relationship to Cleft Lip/Palate PI: Rich Spritz, U of Colorado, Denver Use of the mouse “Collaborative Cross” to identify QTL involved in determining facial shape Quantitative 3D morphometry of all of the viable CC mouse lines using micro-CT imaging Both the raw micro-CT data and morphometric data will be available on the FaceBase site. GWAS of facial shape in humans 3D facial morphometry of Tanzanian children (n >~5700)(all Bantu) 3D mesh images, morphometric data, and genotypes will be available through FaceBase. Will be incorporated in the 3D Facial Norms database format Data will be available from smaller numbers of U.S. children of European Caucasian, Hispanic, and Asian backgrounds as well as Masai children from Tanzania More limited (deidentified) data will also be available through dbGaP

Data available – an example

Shape-Based Retrieval of 3D Craniofacial Data PI: Linda Shapiro, U of Washington https://www.facebase.org/node/159 “development of computational techniques to represent, quantify, and analyze variants of biological morphology from imaging sources, such as CT scans, MRI scans, and stereo cameras” For analysis of 3D mesh images: 2D Azimuth-Elevation Histogram local Features 2D Longitude-Latitude Signature Map pose Normalization automatic Cranial Image Generation Web-based access to these tools using “CranioGUI” java app

How do I get data from FaceBase? Model system and summary human data Easy! These data are considered “open access” all you need is an account on the site request an account on the site at https://www.facebase.org/user/register download data Individual level human data (genotypes, 3D facial mesh images, etc.) a little more involved access controlled by FaceBase Data Access Committee process described on the “official documents” page Home page > Resources > Official documents https://www.facebase.org/content/official-documents

Future developments More data coming Enhanced data integration and search features Gene specific pages gathering all FaceBase data about a particular gene + outside links Dissemination of donated datasets Planning for the next iteration of the consortium NIDCR Home  > Grants & Funding  > See Funding Opportunities Sorted by...  > Concept Clearances (Future Research Directions)  > Concept Clearances

Questions about FaceBase At NIDCR Dr. Steve Scholnick Scholnis@nidcr.nih.gov 301-594-3977 Contact any of the FaceBase PIs