Team RICO (Risk of COVID-19), mentored by Dr. Liz Worthey, won 3rd place in UAB COVID Hackathon

Third prize went to the RICO (RIsk of COvid) team, which adapted credit scorecard models used in the financial industry to create a functioning web app that advises users whether or not they should be tested for COVID-19 based on their symptoms. (Watch the RICO team’s presentation.) Team members were: Tarun Mamidi, doctoral trainee in Genetics, Genomics and Bioinformatics; Thi Tran-Nguyen, Ph.D., committee chair and data scientist for UAB’s U-BRITE/COVID-19 Knowledge Curation Taskforce and a graduate of the doctoral program in immunology; Ryan Melvin, Ph.D., assistant professor of anesthesiology and perioperative medicine; and mentor Elizabeth Worthey, Ph.D., associate professor of pediatric hematology and oncology.

Animation from the RICO team depicting part of their functioning web app for alerting members of the public if they should seek a COVID-19 test. Watch the full presentation here.

More about this news to be found in “The Reporter|UAB”

Elizabeth A. Worthey, Ph.D., was appointed the inaugural holder of the Endowed Professorship in Pediatrics in the Department of Pediatrics

Buildings from below

The University of Alabama System Board of Trustees appointed Mona Fouad, M.D., the inaugural holder of the Edward E. Partridge, M.D., Endowed Chair for Cancer Disparity Research during its June 4 meeting. Matthew Macaluso, D.O., was appointed the first holder of the Bee McWane Reid Endowed Chair in Psychiatry and Neurobiology in the Department of Psychiatry and Behavioral Neurobiology.

Elizabeth A. Worthey, Ph.D., was appointed the inaugural holder of the Endowed Professorship in Pediatrics in the Department of Pediatrics, and Charles Blakely Simpson, M.D., was appointed the first holder of the Abroms Endowed Professorship in the Department of Otolaryngology.

More details to be found here.

CGDS ClinVar Submissions Update

The Center for Computational Genomics and Data Science (CGDS) at the University of Alabama recently submitted updates to ClinVar, highlighting its ongoing contributions to genomic research and variant interpretation.

GeneSubmissionsLast Updated
ENO31Jun 9, 2020
EPHX11Dec 18, 2019
HFE1Dec 18, 2019
LOC1087836451Dec 18, 2019
MBL21Dec 18, 2019
PLG1Dec 18, 2019
SERPINA11Dec 18, 2019

More details about the submission are here.

Applying whole-genome sequencing in relation to phenotype and outcomes in siblings with cystic fibrosis

Abstract

Variations in disease onset and/or severity have often been observed in siblings with cystic fibrosis (CF), despite the same CFTR genotype and environment. We postulated that genomic variation (modifier and/or pharmacogenomic variants) might explain these clinical discordances. From a cohort of patients included in the Wisconsin randomized clinical trial (RCT) of newborn screening (NBS) for CF, we identified two brothers who showed discordant lung disease courses as children, with one milder and the other more severe than average, and a third, eldest brother, who also has severe lung disease. Leukocytes were harvested as the source of DNA, and whole-genome sequencing (WGS) was performed. Variants were identified and analyzed using in-house-developed informatics tools. Lung disease onset and severity were quantitatively different between brothers during childhood. The youngest, less severely affected brother is homozygous for HFE p.H63D. He also has a very rare PLG p.D238N variant that may influence host–pathogen interaction during chronic lung infection. Other variants of interest were found differentially between the siblings. Pharmacogenomics findings were consistent with the middle, most severely affected brother having poor outcomes to common CF treatments. We conclude that genomic variation between siblings with CF is expected. Variable lung disease severity may be associated with differences acting as genetic modifiers and/or pharmacogenomic factors, but large cohort studies are needed to assess this hypothesis.

More about the article at this link

Genome Sequencing for Early-Onset or Atypical Dementia: High Diagnostic Yield and Frequent Observation of Multiple Contributory Alleles

We assessed the results of genome sequencing for early-onset dementia. Participants were selected from a memory disorders clinic. Genome sequencing was performed along with C9orf72 repeat expansion testing. All returned sequencing results were Sanger-validated. Prior clinical diagnoses included Alzheimer’s disease, frontotemporal dementia, and unspecified dementia. The mean age of onset was 54 (41-76). Fifty percent of patients had a strong family history, 37.5% had some, and 12.5% had no known family history. Nine of 32 patients (28%) had a variant defined as pathogenic or likely pathogenic (P/LP) by American College of Medical Genetics and Genomics standards, including variants in APP, C9orf72, CSF1R, and MAPT Nine patients (including three with P/LP variants) harbored established risk alleles with moderate penetrance (odds ratios of ∼2-5) in ABCA7, AKAP9, GBA, PLD3, SORL1, and TREM2 All six patients harboring these moderate penetrance variants but not P/LP variants also had one or two APOE ε4 alleles. One patient had two APOE ε4 alleles with no other established contributors. In total, 16 patients (50%) harbored one or more genetic variants likely to explain symptoms. We identified variants of uncertain significance (VUSs) in ABI3, ADAM10, ARSA, GRID2IP, MME, NOTCH3, PLCD1, PSEN1, TM2D3, TNK1, TTC3, and VPS13C, also often along with other variants. In summary, genome sequencing for early-onset dementia frequently identified multiple established or possible contributory alleles. These observations add support for an oligogenic model for early-onset dementia.

More about the article.