This application will study the oral sequelae in childhood cancer survivors from the St. Jude Life cohort and Childhood Cancer Survivor Study cohort. Both disease onset and onset time were collected, but current analyses fail to analyze the disease onset time due to high rate of missing data. DNA samples were collected and sequenced but not analyzed either. We propose innovative ways to analyze the disease onset time in the presence of missing data by considering some onset time as interval-censored, and propose new methods for analyzing interval-censored outcomes with ultrahigh-dimensional genetic covariates. We will perform both single variant-based and rare variant aggregation-based analysis for the whole genome sequencing data.
We aim to estimate oral disease dynamics and associated risk factors including environmental factors, genetic factors, and their interaction. Specifically, the aims are: 1). Develop nonparametric and semiparametric screening methods for ultrahigh-dimensional data with interval-censored outcomes; 2). Develop a penalized regression method for data with reduced dimensionality from Aim 1; 3). Apply the methods developed in Aim 1 and Aim 2 to the SJLIFE and CCSS data. We will develop and share multiple user-friendly R codes associated with the new methods. The main objective of the proposed research is to employ the existing methods and develop new statistical procedures to perform appropriate analysis on the whole-genome and oral health data for a deeper understanding of the genetic architecture of tooth development and disease.
This proposal will study the adverse oral sequelae in childhood cancer survivors from the St. Jude Life cohort and Childhood Cancer Survivor Study cohort. While current methods fail to analyze the disease onset time and genetic profiles due to complex data structure, this project proposes to develop novel statistical methods to analyze interval- censored time-to-event outcomes with ultrahigh-dimensional genomic data and apply them in two well-established cohorts of childhood cancer survivors. It will potentially provide more in-depth findings on oral diseases to inform or counsel patients.