Virtual machine warmup blows hot and cold

Virtual Machines (VMs) with Just-In-Time (JIT) compilers are traditionally thought to execute programs in two phases: first the warmup phase determines which parts of a program would most benefit from dynamic compilation and JIT compiles them into machine code; after compilation has occurred, the program is said to be at peak performance. When measuring the performance of JIT compiling VMs, data collected during the warmup phase is generally discarded, placing the focus on peak performance. In this paper we first run a number of small, deterministic benchmarks on a variety of well known VMs, before introducing a rigorous statistical model for determining when warmup has occurred. Across 3 benchmarking machines only 43.3–56.5% of (VM, benchmark) pairs conform to the traditional view of warmup and none of the VMs consistently warms up

Bayesian detection of abnormal segments in multiple time series

We present a novel Bayesian approach to analysing multiple time-series with the aim of detecting abnormal regions. These are regions where the properties of the data change from some normal or baseline behaviour. We allow for the possibility that such changes will only be present in a, potentially small, subset of the time-series. We develop a general model for this problem, and show how it is possible to accurately and efficiently perform Bayesian inference, based upon recursions that enable independent sampling from the posterior distribution. A motivating application for this problem comes from detecting copy number variation (CNVs), using data from multiple individuals. Pooling information across individuals can increase the power of detecting CNVs, but often a specific CNV will only be present in a small subset of the individuals. We evaluate the Bayesian method on both simulated and real CNV data, and give evidence that this approach is more accurate than a recently proposed method for analysing such data

Simulator adaptation at runtime for component-based simulation software

Component-based simulation software can provide many opportunities to compose and configure simulators, resulting in an algorithm selection problem for the user of this software. This thesis aims to automate the selection and adaptation of simulators at runtime in an application-independent manner. Further, it explores the potential of tailored and approximate simulators - in this thesis concretely developed for the modeling language ML-Rules - supporting the effectiveness of the adaptation scheme.Komponenten-basierte Simulationssoftware kann viele Möglichkeiten zur Komposition und Konfiguration von Simulatoren bieten und damit zu einem Konfigurationsproblem für Nutzer dieser Software führen. Das Ziel dieser Arbeit ist die Entwicklung einer generischen und automatisierten Auswahl- und Adaptionsmethode für Simulatoren. Darüber hinaus wird das Potential von spezifischen und approximativen Simulatoren anhand der Modellierungssprache ML-Rules untersucht, welche die Effektivität des entwickelten Adaptionsmechanismus erhöhen können

Pervasive lesion segregation shapes cancer genome evolution

Cancers arise through the acquisition of oncogenic mutations and grow through clonal expansion. Here we reveal that most mutagenic DNA lesions are not resolved as mutations within a single cell-cycle. Instead, DNA lesions segregate unrepaired into daughter cells for multiple cell generations, resulting in the chromosome-scale phasing of subsequent mutations. We characterise this process in mutagen-induced mouse liver tumours and show that DNA replication across persisting lesions can produce multiple alternative alleles in successive cell divisions, thereby generating both multi-allelic and combinatorial genetic diversity. The phasing of lesions enables the accurate measurement of strand biased repair processes, quantification of oncogenic selection, and fine mapping of sister chromatid exchange events. Finally, we demonstrate that lesion segregation is a unifying property of exogenous mutagens, including UV light and chemotherapy agents in human cells and tumours, which has profound implications for the evolution and adaptation of cancer genomes.This work was supported by: Cancer Research UK (20412, 22398), the European Research Council (615584, 682398), the Wellcome Trust (WT108749/Z/15/Z, WT106563/Z/14/A, WT202878/B/16/Z), the European Molecular Biology Laboratory, the MRC Human Genetics Unit core funding programme grants (MC_UU_00007/11, MC_UU_00007/16), and the ERDF/Spanish Ministry of Science, Innovation and Universities-Spanish State Research Agency/DamReMap Project (RTI2018-094095-B-I00)

Change-point model on nonhomogeneous Poisson processes with application in copy number profiling by next-generation DNA sequencing

We propose a flexible change-point model for inhomogeneous Poisson Processes, which arise naturally from next-generation DNA sequencing, and derive score and generalized likelihood statistics for shifts in intensity functions. We construct a modified Bayesian information criterion (mBIC) to guide model selection, and point-wise approximate Bayesian confidence intervals for assessing the confidence in the segmentation. The model is applied to DNA Copy Number profiling with sequencing data and evaluated on simulated spike-in and real data sets.Comment: Published in at http://dx.doi.org/10.1214/11-AOAS517 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org