Survival Analysis Commons^™

Replication And Extension Of Kras-Associated Gene Expression Signatures In Lung Adenocarcinoma: A Cox Proportional Hazards Analysis Of Mutation Status, Gene Expression, Multi-Gene Mutation Count, And Ras De Novo Signature, Camryn Berry

Theses & Dissertations

This study evaluates the robustness and reproducibility of a previously published analysis of lung adenocarcinoma gene expression data (Schabath et al.), which examined KRAS-associated biology in relation to co-occurring STK11 and TP53 mutations. The original study used Kaplan-Meier (KM) survival analysis and gene expression signatures to assess associations between driver mutations, tumor suppressor mutations, and patient outcomes. The aim of this work is to replicate these analyses and evaluate consistency across independent datasets (Wilkerson and Selamat), with extension using Cox proportional hazards (PH) models. Two hypotheses are evaluated: (1) that the number of mutated genes increases the hazard of death, …

Approximate Likelihood Based Estimations For Joint Models With Intractable Likelihoods, Karl Stessy M. Bisselou

Theses & Dissertations

This dissertation focuses on the development of approximation approaches for the joint modeling (JM) of repeated measures data and time-to-event data in the presence of analytically or numerically intractable likelihoods. Current likelihood-based inferences for JMs show several limitations including (i) intractability of integrals during marginal likelihood derivations due to the complexity in computations, and (ii) the large number of nuisance parameters (unobserved) posing a problem with convergence. The h-likelihood (HL) and synthetic likelihood (SL) are two computationally efficient estimation approaches that overcome these challenges.

In the presence of extremely high censoring rates, the HL can produce bias parameter estimates. We …