Browsing by Author "McCabe, Sean D."

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    ACTOR: a latent Dirichlet model to compare expressed isoform proportions to a reference panel
    (Oxford University Press, 2023) McCabe, Sean D.; Nobel, Andrew B.; Love, Michael I.; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
    The relative proportion of RNA isoforms expressed for a given gene has been associated with disease states in cancer, retinal diseases, and neurological disorders. Examination of relative isoform proportions can help determine biological mechanisms, but such analyses often require a per-gene investigation of splicing patterns. Leveraging large public data sets produced by genomic consortia as a reference, one can compare splicing patterns in a data set of interest with those of a reference panel in which samples are divided into distinct groups, such as tissue of origin, or disease status. We propose A latent Dirichlet model to Compare expressed isoform proportions TO a Reference panel (ACTOR), a latent Dirichlet model with Dirichlet Multinomial observations to compare expressed isoform proportions in a data set to an independent reference panel. We use a variational Bayes procedure to estimate posterior distributions for the group membership of one or more samples. Using the Genotype-Tissue Expression project as a reference data set, we evaluate ACTOR on simulated and real RNA-seq data sets to determine tissue-type classifications of genes. ACTOR is publicly available as an R package at https://github.com/mccabes292/actor.
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    Coronary Artery Calcifications and Cardiac Risk after Radiotherapy for Stage III Lung Cancer
    (Elsevier, 2022) Wang, Kyle; Malkin, Hayley E.; Patchett, Nicholas D.; Pearlstein, Kevin A.; Heiling, Hillary M.; McCabe, Sean D.; Deal, Allison M.; Mavroidis, Panayiotis; Oakey, Mary; Fenoli, Jeffrey; Lee, Carrie B.; Klein, J. Larry; Jensen, Brian C.; Stinchcombe, Thomas E.; Marks, Lawrence B.; Weiner, Ashley A.; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
    Purpose: Heart dose and heart disease increase the risk for cardiac toxicity associated with radiation therapy. We hypothesized that computed tomography (CT) coronary calcifications are associated with cardiac toxicity and may help ascertain baseline heart disease. Methods and materials: We analyzed the cumulative incidence of cardiac events in patients with stage III non-small cell lung cancer receiving median 74 Gy on prospective dose-escalation trials. Events were defined as symptomatic effusion, pericarditis, unstable angina, infarction, significant arrhythmia, and/or heart failure. Coronary calcifications were delineated on simulation CTs using radiation software program (130 HU threshold). Calcifications were defined as "none," "low," and "high," with median volume dividing low and high. Results: Of 109 patients, 26 had cardiac events at median 26 months (range, 1-84 months) after radiation therapy. Median follow-up in surviving patients was 8.8 years (range, 2.3-17.3). On simulation CTs, 64 patients (59%) had coronary calcifications with median volume 0.2 cm3 (range, 0.01-8.3). Only 16 patients (15%) had baseline coronary artery disease. Cardiac events occurred in 7% (3 of 45), 29% (9 of 31), and 42% (14 of 33) of patients with no, low, and high calcifications, respectively. Calcification burden was associated with cardiac toxicity on univariate (low vs none: hazard ratio [HR] 5.0, P = .015; high vs none: HR 8.1, P < .001) and multivariate analyses (low vs none: HR 7.0, P = .005, high vs none: HR 10.6, P < .001, heart mean dose: HR 1.1/Gy, P < .001). Four-year competing risk-adjusted event rates for no, low, and high calcifications were 4%, 23%, and 34%, respectively. Conclusions: The presence of coronary calcifications is a cardiac risk factor that can identify high-risk patients for medical referral and help guide clinicians before potentially cardiotoxic cancer treatments.