Bayesian variable selection in clustering via dirichlet process mixture models

The increased collection of high-dimensional data in various fields has raised a strong interest in clustering algorithms and variable selection procedures. In this disserta- tion, I propose a model-based method that addresses the two problems simultane- ously. I use Dirichlet process mixture models to define the cluster structure and to introduce in the model a latent binary vector to identify discriminating variables. I update the variable selection index using a Metropolis algorithm and obtain inference on the cluster structure via a split-merge Markov chain Monte Carlo technique. I evaluate the method on simulated data and illustrate an application with a DNA microarray study. I also show that the methodology can be adapted to the problem of clustering functional high-dimensional data. There I employ wavelet thresholding methods in order to reduce the dimension of the data and to remove noise from the observed curves. I then apply variable selection and sample clustering methods in the wavelet domain. Thus my methodology is wavelet-based and aims at clustering the curves while identifying wavelet coefficients describing discriminating local features. I exemplify the method on high-dimensional and high-frequency tidal volume traces measured under an induced panic attack model in normal humans

Analysis of protein complexes through model‐based biclustering of label‐free quantitative AP‐MS data

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102630/1/msb201041.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102630/2/msb201041-sup-0001.pd

The consideration of post-exercise impact on SCAT3 scores in athletes immediately following a head injury

Examine effects of high-intensity exercise and physical impacts during rugby match on self-report symptoms in The Sport Concussion Assessment Tool (SCAT3), and its ability to differentiate head-injured players from controls. Methods: Symptoms were assessed immediately following completion of a rugby match (median 60 minutes). Players removed from the match for assessment due to a head hit were classified as head injured. Controls completed match without head hit. Results: 209 players (67 female; 33 ± 13 years) participated with 80 experiencing a head injury. Symptom severity was significantly greater in head injured (26.2 ± 17.6) compared with controls (8.9 ± 11.5, P 16 symptom severity, misclassifying them as suspected concussion. There were no significant sex differences. Factor analysis produced four symptom clusters of which Headache was most discriminatory between the head injured (median = 1.7) and controls (median = 0.0). Conclusion: These findings demonstrate that exercise and contact during a game affect symptom assessment, increasing the likelihood of misclassifying players with suspected concussion. Factor characterization of symptoms associated with head injury using an exercised comparison group provides more useful discrimination. These results highlight the necessity for objective measures to diagnose concussions outside of symptom self-report

Analysis of protein complexes through model‐based biclustering of label‐free quantitative AP‐MS data

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102630/1/msb201041.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102630/2/msb201041-sup-0001.pd

Clinical Study Evaluation of Diabetic Patients with Breast Cancer Treated with Metformin during Adjuvant Radiotherapy

. Purpose. The purpose of this study was to evaluate acute locoregional toxicity in patients with breast cancer receiving concurrent metformin plus radiation therapy. Methods and Materials. Diabetic breast cancer patients receiving concurrent metformin and radiation therapy were matched with nondiabetic patients and diabetic patients using an alternative diabetes medication. Primary endpoints included the presence of a treatment break and development of dry or moist desquamation. Results. There was a statistically significant increase in treatment breaks for diabetic patients receiving concurrent metformin when compared to the nondiabetic patients ( value = 0.02) and a trend toward significance when compared to diabetic patients receiving an alternate diabetes medication ( value = 0.08). Multiple logistic regression analysis demonstrated concurrent metformin use as being associated with a trend toward the predictive value of determining the incidence of developing desquamation in diabetic patients receiving radiation therapy compared to diabetic patients receiving an alternate diabetes medication ( value = 0.06). Conclusions. Diabetic patients treated with concurrent metformin and radiation therapy developed increased acute locoregional toxicity in comparison with diabetic patients receiving an alternate diabetes medication and nondiabetic patients. Further clinical investigation should be conducted to determine the therapeutic ratio of metformin in combination with radiation therapy

Clinically Relevant Characterization of Lung Adenocarcinoma Subtypes Based on Cellular Pathways: An International Validation Study

Lung adenocarcinoma (AD) represents a predominant type of lung cancer demonstrating significant morphologic and molecular heterogeneity. We sought to understand this heterogeneity by utilizing gene expression analyses of 432 AD samples and examining associations between 27 known cancer-related pathways and the AD subtype, clinical characteristics and patient survival. Unsupervised clustering of AD and gene expression enrichment analysis reveals that cell proliferation is the most important pathway separating tumors into subgroups. Further, AD with increased cell proliferation demonstrate significantly poorer outcome and an increased solid AD subtype component. Additionally, we find that tumors with any solid component have decreased survival as compared to tumors without a solid component. These results lead to the potential to use a relatively simple pathological examination of a tumor in order to determine its aggressiveness and the patient's prognosis. Additional results suggest the ability to use a similar approach to determine a patient's sensitivity to targeted treatment. We then demonstrated the consistency of these findings using two independent AD cohorts from Asia (N = 87) and Europe (N = 89) using the identical analytic procedures