Open source: How data scientist Liz Worthey is bringing precision medicine to the people
Elizabeth “Liz” Worthey joined UAB this summer to help open up genetic insights as a routine part of clinical care. “You have to actually have a health care system to put [genomic diagnostics] into health care,” Worthey said. “That’s why I’m at UAB.”
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VarSight: prioritizing clinically reported variants with binary classification algorithms
When applying genomic medicine to a rare disease patient, the primary goal is to identify one or more genomic variants that may explain the patient’s phenotypes. Typically, this is done through annotation, filtering, and then prioritization of variants for manual curation. However, prioritization of variants in rare disease patients remains a challenging task due to the high degree of variability in phenotype presentation and molecular source of disease. Thus, methods that can identify and/or prioritize variants to be clinically reported in the presence of such variability are of critical importance.
We tested the application of classification algorithms that ingest variant annotations along with phenotype information for predicting whether a variant will ultimately be clinically reported and returned to a patient. To test the classifiers, we performed a retrospective study on variants that were clinically reported to 237 patients in the Undiagnosed Diseases Network.
We treated the classifiers as variant prioritization systems and compared them to four variant prioritization algorithms and two single-measure controls. We showed that the trained classifiers outperformed all other tested methods with the best classifiers ranking 72% of all reported variants and 94% of reported pathogenic variants in the top 20.
We demonstrated how freely available binary classification algorithms can be used to prioritize variants even in the presence of real-world variability. Furthermore, these classifiers outperformed all other tested methods, suggesting that they may be well suited for working with real rare disease patient datasets.
Worthey appointed to pediatric and pathology director positions
Elizabeth Worthey, Ph.D., has joined the University of Alabama at Birmingham’s Department of Pediatrics as the director for the Center for Genomic Data Sciences. Additionally, she will serve in the Department of Pathology as the director of the Bioinformatics Section in the Division of Genomics Diagnostics and Bioinformatics. She is also the new associate director for the Hugh Kaul Precision Medicine Institute.
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Liz Worthey to join Precision Medicine Institute
Liz Worthey to join as an Associate Director in the Hugh Kaul Precision Medicine InstituteSchool of Medicine.
Risk-factors Associated With Poor Outcomes in VEO-IBD Secondary to XIAP Deficiency: A Case Report and Literature Review
Very early onset inflammatory bowel disease (VEO-IBD) represents a diagnostic and treatment challenge. Here we present a case of VEO-IBD secondary to a mutation in BIRC4 gene, which encodes X-linked inhibitor of apoptosis protein (XIAP), in a 17-month-old boy with severe failure to thrive, intractable diarrhea, and hepatosplenomegaly. Endoscopy and histology identified only mild duodenitis and ileitis, but severe pancolitis with crypt abscesses and epithelium apoptosis. Minimal improvement in symptoms was achieved with total parenteral nutrition (TPN), intravenous (IV) corticosteroids, and tacrolimus, whereas induction and maintenance therapy with adalimumab led to complete remission. After 6 months, the patient developed hemophagocytic lymphohistiocytosis and eventually died due to multisystem organ failure. A review of the literature revealed that some patients with VEO-IBD secondary to XIAP deficiency develop symptoms that are refractory to medical and surgical management, while initial reports suggest that allogeneic hematopoietic stem cell transplantation (HSCT), with reduced intensity conditioning, can successfully induce long-lasting remission and may even be curative. We propose that in patients with XIAP deficiency a constellation of symptoms including colitis at an early age, severe failure to thrive, and splenomegaly/hepatosplenomegaly can identify a subgroup of patients at high risk of experiencing medically refractory IBD phenotype and increased mortality. Hematopoietic stem cell transplant should be considered early in these high-risk patients, as it may resolve both their intestinal inflammation and a risk of developing life threatening hemophagocytic lymphohistiocytosis .
Dr. Worthey to join Department of Pediatrics as Director of Center for Genomic Data Sciences
We are excited for Dr. Worthey to bring her expertise in diagnostics, genome informatics and data science to UAB and the Departments of Pediatrics and Pathology and look forward to her leadership in expanding our informatics and precision medicine goals to improve the clinical care of the children of Alabama.
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Whole Genome Sequencing and Analysis of ME/CFS
Check out Dr. Worthey’s presentation on ME/CFS in a webinar hosted by SolveCFS.