Spatial clustering of array CGH features in combination with hierarchical multiple testing

We propose a new approach for clustering DNA features using array CGH data from multiple tumor samples. We distinguish data-collapsing: joining contiguous DNA clones or probes with extremely similar data into regions, from clustering: joining contiguous, correlated regions based on a maximum likelihood principle. The model-based clustering algorithm accounts for the apparent spatial patterns in the data. We evaluate the randomness of the clustering result by a cluster stability score in combination with cross-validation. Moreover, we argue that the clustering really captures spatial genomic dependency by showing that coincidental clustering of independent regions is very unlikely. Using the region and cluster information, we combine testing of these for association with a clinical variable in an hierarchical multiple testing approach. This allows for interpreting the significance of both regions and clusters while controlling the Family-Wise Error Rate simultaneously. We prove that in the context of permutation tests and permutation-invariant clusters it is allowed to perform clustering and testing on the same data set. Our procedures are illustrated on two cancer data sets

Stateful Testing: Finding More Errors in Code and Contracts

Automated random testing has shown to be an effective approach to finding faults but still faces a major unsolved issue: how to generate test inputs diverse enough to find many faults and find them quickly. Stateful testing, the automated testing technique introduced in this article, generates new test cases that improve an existing test suite. The generated test cases are designed to violate the dynamically inferred contracts (invariants) characterizing the existing test suite. As a consequence, they are in a good position to detect new errors, and also to improve the accuracy of the inferred contracts by discovering those that are unsound. Experiments on 13 data structure classes totalling over 28,000 lines of code demonstrate the effectiveness of stateful testing in improving over the results of long sessions of random testing: stateful testing found 68.4% new errors and improved the accuracy of automatically inferred contracts to over 99%, with just a 7% time overhead.Comment: 11 pages, 3 figure