Using ClinGenDB for Curation

Sharon E. Plon, MD, PhD, FACMG

ClinGenDB Disease Area Curation Tool

ClinVar/ClinGen System Interactions

OMIM

Patient Registries

EHR Interface

Expert Curation of Genes and Variants by Clinical Domain and Disease Area Workgroups

dbGaP

LSDBs

Labs Labs

Labs (Genotypes & Phenotypes)

Gene Resource

(Medical Exome, Actionability)

CNV Curation

Tool (JIRA)

Application Interface

External Informatics Activities Enabled

Expert Curated Variants

Case-level Data

Variant-level Data ClinVar

Disease WGs

Clinical Domain WGs

Data

Crowd- sourced Curation

Controlled Access

Public Access

Private

Pharm GKB

Machine Learning Algorithms

Population Datasets

Medical Lit

Portal for the Public

ClinGenDB

Design and Implementation Team

Aleksandar Milosavljevic, PhD Bioinformatics Research Laboratory (BRL)

BCM Contributors: Hailin Chen, Xin Feng,

Andrew R. Jackson, Sameer Paithankar, Sharon Plon Stanford Contributors: Tam Sneddon, Mike Cherry,

Carlos Bustamante

ClinGenDB Design and Implementation 1. Curation Tools and Interfaces 2. Application Programming Interfaces (APIs) 3. Database Features and Document Models 4. Data Import From and Export Into ClinVar 5. Data Linking / Import from Other Sources

ClinGenDB – Data Entry – MYO6

Edit documents determined by user’s role.

• i.e. in the Genboree group containing the knowledgebase.

Search (initially) by document/ variant name.

Aleks Milosavljevic and colleagues

ClinGenDB – Literature extraction - PTEN

Comprehensive records, with facts extracted into sub-properties.

“Literature Curation Evidence” is an open-ended list of 0+ “publicationTitle” sub-properties. • Can add many many more.

Data Linking / Import from Open Sources Accomplished • Identified computer/API-accessible LSDBs for 56 ACMG

genes • Identified unique variants not covered by ClinVar (Xin

and Steven) • Annotation of imported variants using population data (dbSNP, 1000 genomes, ESP6500)

In Progress • Implement links to LSDB records from variant entries in ClinGenDB to facilitate variant curation • Assessing the quality of LSDBs (Steven)

• Amount of curation, submission type, phenotype information, etc.

Future • Design and implement methods for data linking or import from LSDBs and other sources

ClinGenDB linking to external databases

Data Import From and Export Into ClinVar Accomplished • Import of data from the ClinVar VCF file

In Progress

• Import of data from the ClinVar XML file • Issues being populated in JIRA

• Export of data into ClinVar • Now working on the ClinVar “minimal-submission”

process • Document the details of data-flow between ClinGen and

ClinVar Future • Make modifications to support the new data model under

development by the Data Model WG • Implement an ID system for variants in ClinGen

Curation Tools and Interfaces Accomplished • Working prototype of interface implemented and tested with a single user (Tam Sneddon) • First cycle of feedback collected using ticketing system and used to improve the interface

In Progress • Tool that automatically generates and justifies preliminary pathogenicity assertion based on ACMG guidelines

Future • Implement new ACMG variant classification guidelines

upon their official approval • Update document to be consistent with new data model • Support a curation jamboree

Questions?