Informatics & Analysis

The Informatics Working Group aims to coordinate the acquisition, analysis, and dissemination of ClinGen resource data.


  1. Finalize system map for ClinGen informatics activities
  2. Design and develop user-facing tools for accessing ClinGenDB and related data sources. Select and implement existing curation tools as recommended by expert curators.
  3. Establish process/tools for extracting data from ClinVar and other sources for use in ClinGenDB
  4. Implement agreed-upon data access levels and requirements within ClinGenDB
  5. Develop novel methods for data analysis
  6. Develop a database to house case-level and individual level data

Projects & Initiatives

  • Gene-Level Modeling

    MotivationVariants in coding and regulatory regions of genes are likely to be the most relevant for disease association. While many bioinformatics tools have been developed for predicting the effect of missense mutations, their accuracy is still far from ideal, reaching about 80% for the best-performing tools. We are attempting here to improve the performance of existing computational methods when applied to specific genes, including the ACMG genes. ApproachIncorrect protein folding and decreased stability are the major consequences of pathogenic missense mutations that lead to diseases. Our...
  • Genome-Wide Modeling

    MotivationInterpreting the clinical significance of rare and novel genetic variants identified in whole-genome sequencing studies remains a critical challenge for patient care. Methods to predict the clinical significance of genetic variants that lie outside of protein coding sequences are particularly under-studied. We aim to develop predictive algorithms that apply to noncoding, intronic, and synonymous variants to complement available approaches for protein-altering missense variants.ApproachOne important mechanism by which genetic variants can achieve clinical significance is thro...
  • Experimental Validation

    MotivationValidation of computational predictions of the clinical significance of genetic variants is an essential step in determining the clinical utility of these approaches. For many variants, experimental functional studies will play an important role in complementing limited available clinical data on pathogenicity.ApproachWe are using a number of molecular tools to experimentally validate the predicted functional effects of genetic variants. These include CRISPR/Cas9-based genome editing to introduce mutations in relevant cell types, as well as the development of high-throughput assays ...

Leadership & Members

Carlos Bustamante, PhD
Principal Investigator, U01 HG007436 grant