Testing clonality of three and more tumors using their loss of heterozygosity profiles
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Irina Ostrovnaya
Abstract
Cancer patients often develop multiple malignancies that may be either metastatic spread of a previous cancer (clonal tumors) or new primary cancers (independent tumors). If diagnosis cannot be easily made on the basis of the pathology review, the patterns of somatic mutations in the tumors can be compared. Previously we have developed statistical methods for testing clonality of two tumors using their loss of heterozygosity (LOH) profiles at several candidate markers. These methods can be applied to all possible pairs of tumors when multiple tumors are analyzed, but this strategy can lead to inconsistent results and loss of statistical power. In this work we will extend clonality tests to three and more malignancies from the same patient. A non-parametric test can be performed using any possible subset of tumors, with the subsequent adjustment for multiple testing. A parametric likelihood model is developed for 3 or 4 tumors, and it can be used to estimate the phylogenetic tree of tumors. The proposed tests are more powerful than combination of all possible pairwise tests.
©2012 Walter de Gruyter GmbH & Co. KG, Berlin/Boston
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Articles in the same Issue
- Article
- A New Explained-Variance Based Genetic Risk Score for Predictive Modeling of Disease Risk
- Hessian Calculation for Phylogenetic Likelihood based on the Pruning Algorithm and its Applications
- Cluster-Localized Sparse Logistic Regression for SNP Data
- How to analyze many contingency tables simultaneously in genetic association studies
- Incorporating the Empirical Null Hypothesis into the Benjamini-Hochberg Procedure
- Estimating the Number of One-step Beneficial Mutations
- Testing clonality of three and more tumors using their loss of heterozygosity profiles
- Correction for Founder Effects in Host-Viral Association Studies via Principal Components
- A Non-Homogeneous Dynamic Bayesian Network with Sequentially Coupled Interaction Parameters for Applications in Systems and Synthetic Biology
- An Integrated Hierarchical Bayesian Model for Multivariate eQTL Mapping
- A Novel and Fast Normalization Method for High-Density Arrays
- Performance of MAX Test and Degree of Dominance Index in Predicting the Mode of Inheritance
- A Bayesian autoregressive three-state hidden Markov model for identifying switching monotonic regimes in Microarray time course data
- QTL Mapping Using a Memetic Algorithm with Modifications of BIC as Fitness Function
- Computing Posterior Probabilities for Score-based Alignments Using ppALIGN
