Clinical and Translational Informatics Solutions for Pediatric Genomic Medicine
When the Human Genome Project was completed in 2003, Francis Collins predicted that a variety of maladies including Alzheimer’s, Parkinson’s, diabetes and cancer would all be cured by virtue of our detailed knowledge of the human genome. While this has not happened, the genetic basis for a growing number of rare, monogenic diseases has been discovered, powered in part by the rapidly falling cost of sequencing. Despite this, it can still take several years for children with rare genetic diseases to obtain a definitive diagnosis and longer still for this diagnosis to influence care.
The Chaudhari Lab is interested in developing, implementing and evaluating strategies to improve the integration of timely genetic diagnosis into clinical care, emphasizing that pediatric genomic medicine is a vital component of a learning health system. Its team uses techniques from a variety of disciplines including data science, natural language processing, machine learning, user centered design, psychometrics and statistical process control to integrate genomic medicine into clinical care and study the impact of this paradigm shift in clinical care.
Areas of Research
The Chaudhari Lab conducts rapid genome sequencing (with or without transcriptomics and metagenomics) on samples from patients identified by clinical geneticists as likely to benefit from obtaining a molecular diagnosis in days rather than weeks (typically patients in intensive care units or those being considered for transplantation).
In addition to assessing test performance characteristics and tracking outcomes, opportunities exist for ancillary studies seeking follow-up with clinicians and/or patients and families as well as gene discovery in selected cases.
While the cost and time required to conduct whole genome sequencing has fallen rapidly, phenotyping remains a largely manual exercise.
The Chaudhari Lab develops, evaluates and implements tools and approaches to automated phenotyping with a focus on performance in scenarios relevant to the practice of pediatric rare disease genomic medicine.
Only 30% of patients referred for whole exome or genome sequencing for suspected rare monogenic disease will obtain a diagnosis at the time of initial assessment with these technologies. Recent research suggests, however, that another 10% can be subsequently diagnosed on reanalysis.
Current practices support reanalysis primarily at the request of a clinician. This research focuses on developing, implementing and evaluating informatics approaches to prioritizing selected cases for laboratory-initiated reanalysis.
The current practice of pediatric genomic medicine for rare diseases is focused on resequencing with short read technologies because this approach is very cost effective. Underpinning this approach is the use of population allele frequency data and the rare disease-rare variant hypothesis to rapidly exclude large number of variants as not being plausible causes of rare disease.
While it has long been known that genomic diversity is significantly higher in populations of African ancestry as compared to populations of European or other non-African ancestry, individuals of African ancestry remain underrepresented in the databases of human genetic variation used. The functional consequence is that when individuals of African ancestry participate in pediatric genomic medicine, they have significantly more variants for the lab to review (slowing interpretation) and more variants of uncertain significance are reported increasing the complexity of post-test genetic counseling, decreasing patient and family satisfaction and making it harder to get other families from similar communities to participate in pediatric genomic medicine research and/or clinical care.
Central Ohio has one of the world’s largest Somali diaspora communities. This research seeks to find culturally competent ways to engage this community in pediatric genomic medicine research and ultimately to sequence enough Somali individuals to accurately assess the allele frequencies of genetic variants in this underserved population.
While pediatric genomic medicine was historically delivered in medical genetics clinics, making this approach to care more accessible will require non-geneticists to become more engaged with specific aspects of this approach. Some basic knowledge of clinical genomics will be vital for almost all members of the health care team.
This research seeks to develop a validated instrument which measures genomic medicine knowledge amongst members of pediatric healthcare teams.
Join the IGM Team
The team at the Institute for Genomic Medicine is growing. Click the link below to view current job listings and to learn more about careers at Nationwide Children's Hospital.
