radiation-planning-assistant-streamlined-fully-automated-radiotherapy

Radiation Planning Assistant - A Streamlined, Fully Automated Radiotherapy Treatment Planning System

The Radiation Planning Assistant (RPA) is a system developed for the fully automated creation of radiotherapy treatment plans, including volume-modulated ...

University of Texas MD Anderson Cancer Center

Folate metabolism, with its importance to DNA repair, provides a promising region for genetic investigation of lung cancer risk. This project investigates genes (MTHFR, MTR, MTRR, CBS, SHMT1, TYMS), folate metabolism related nutrients (B vitamins, methionine, choline, and betaine) and their gene-nutrient interactions.

Investigating multiple candidate genes and nutrients in the folate metabolism pathway to detect genetic and nutritional risk factors for lung cancer.

In this paper, we propose a Bayesian approach to inference on multiple Gaussian graphical models. Specifically, we address the problem of inferring multiple undirected networks in situations where some of the networks may be unrelated, while others share common features. We link the estimation of the graph structures via a Markov random field (MRF) prior which encourages common edges. We learn which sample groups have a shared graph structure by placing a spike-and-slab prior on the parameters that measure network relatedness. This approach allows us to share information between sample groups, when appropriate, as well as to obtain a measure of relative network similarity across groups. Our modeling framework incorporates relevant prior knowledge through an edge-specific informative prior and can encourage similarity to an established network. Through simulations, we demonstrate the utility of our method in summarizing relative network similarity and compare its performance against related methods. We find improved accuracy of network estimation, particularly when the sample sizes within each subgroup are moderate. We also illustrate the application of our model to infer protein networks for various cancer subtypes and under different experimental conditions.

Bayesian Inference of Multiple Gaussian Graphical Models.

In this work, we develop a Bayesian approach to perform selection of predictors that are linked within a network. We achieve this by combining a sparse regression model relating the predictors to a response variable with a graphical model describing conditional dependencies among the predictors. The proposed method is well-suited for genomic applications because it allows the identification of pathways of functionally related genes or proteins that impact an outcome of interest. In contrast to previous approaches for network-guided variable selection, we infer the network among predictors using a Gaussian graphical model and do not assume that network information is available a priori. We demonstrate that our method outperforms existing methods in identifying network-structured predictors in simulation settings and illustrate our proposed model with an application to inference of proteins relevant to glioblastoma survival.

Joint Bayesian variable and graph selection for regression models with network-structured predictors.

With the rise of both the number and the complexity of traits of interest, control of the false discovery rate (FDR) in genetic association studies has become an increasingly appealing and accepted target for multiple comparison adjustment. While a number of robust FDR-controlling strategies exist, the nature of this error rate is intimately tied to the precise way in which discoveries are counted, and the performance of FDR-controlling procedures is satisfactory only if there is a one-to-one correspondence between what scientists describe as unique discoveries and the number of rejected hypotheses. The presence of linkage disequilibrium between markers in genome-wide association studies (GWAS) often leads researchers to consider the signal associated to multiple neighboring SNPs as indicating the existence of a single genomic locus with possible influence on the phenotype. This a posteriori aggregation of rejected hypotheses results in inflation of the relevant FDR. We propose a novel approach to FDR control that is based on prescreening to identify the level of resolution of distinct hypotheses. We show how FDR-controlling strategies can be adapted to account for this initial selection both with theoretical results and simulations that mimic the dependence structure to be expected in GWAS. We demonstrate that our approach is versatile and useful when the data are analyzed using both tests based on single markers and multiple regression. We provide an R package that allows practitioners to apply our procedure on standard GWAS format data, and illustrate its performance on lipid traits in the North Finland Birth Cohort 66 cohort study.

Controlling the Rate of GWAS False Discoveries.

Colorectal cancers are common tumors in the United States and appropriate imaging is essential to direct appropriate care. Staging and treatment differs between tumors arising in the colon versus the rectum. Local staging for colon cancer is less integral to directing therapy given radical resection is often standard. Surgical options for rectal carcinoma are more varied and rely on accurate assessment of the sphincter, circumferential resection margins, and peritoneal reflection. These important anatomic landmarks are best appreciated on high-resolution imaging with transrectal ultrasound or MRI. When metastatic disease is suspected, imaging modalities that provide a global view of the body, such as CT with contrast or PET/CT may be indicated. Rectal cancer often metastasizes to the liver and so MRI of the liver with and without contrast provides accurate staging for liver metastases. This article focuses on local and distant staging and reviews the appropriateness of different imaging for both variants. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness CriteriaPretreatment Staging of Colorectal Cancer.

By analyzing multitissue gene expression and genome-wide genetic variation data in samples from a vervet monkey pedigree, we generated a transcriptome resource and produced the first catalog of expression quantitative trait loci (eQTLs) in a nonhuman primate model. This catalog contains more genome-wide significant eQTLs per sample than comparable human resources and identifies sex- and age-related expression patterns. Findings include a master regulatory locus that likely has a role in immune function and a locus regulating hippocampal long noncoding RNAs (lncRNAs), whose expression correlates with hippocampal volume. This resource will facilitate genetic investigation of quantitative traits, including brain and behavioral phenotypes relevant to neuropsychiatric disorders.

Article	Year
Investigating multiple candidate genes and nutrients in the folate metabolism pathway to detect genetic and nutritional risk factors for lung cancer. PloS one\| PubMed ID: 23372658	2013
Bayesian Inference of Multiple Gaussian Graphical Models. Journal of the American Statistical Association\| PubMed ID: 26078481	2015
Joint Bayesian variable and graph selection for regression models with network-structured predictors. Statistics in medicine\| PubMed ID: 26514925	2016
Controlling the Rate of GWAS False Discoveries. Genetics\| PubMed ID: 27784720	2017
ACR Appropriateness CriteriaPretreatment Staging of Colorectal Cancer. Journal of the American College of Radiology : JACR\| PubMed ID: 28473079	2017
Genetic variation and gene expression across multiple tissues and developmental stages in a nonhuman primate. Nature genetics\| PubMed ID: 29083405	2017

Christine Peterson

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