Variation in pre-PCR processing of FFPE samples leads to discrepancies in BRAF and EGFR mutation detection: a diagnostic RING trial.

AIMS: Mutation detection accuracy has been described extensively; however, it is surprising that pre-PCR processing of formalin-fixed paraffin-embedded (FFPE) samples has not been systematically assessed in clinical context. We designed a RING trial to (i) investigate pre-PCR variability, (ii) correlate pre-PCR variation with EGFR/BRAF mutation testing accuracy and (iii) investigate causes for observed variation. METHODS: 13 molecular pathology laboratories were recruited. 104 blinded FFPE curls including engineered FFPE curls, cell-negative FFPE curls and control FFPE tissue samples were distributed to participants for pre-PCR processing and mutation detection. Follow-up analysis was performed to assess sample purity, DNA integrity and DNA quantitation. RESULTS: Rate of mutation detection failure was 11.9%. Of these failures, 80% were attributed to pre-PCR error. Significant differences in DNA yields across all samples were seen using analysis of variance (p

A Scalable General Purpose System for Large-Scale Graph Processing

Graph analytics is an important and computationally demanding class of data analytics. It is essential to balance scalability, ease-of-use and high performance in large scale graph analytics. As such, it is necessary to hide the complexity of parallelism, data distribution and memory locality behind an abstract interface. The aim of this work is to build a scalable graph analytics framework that does not demand significant parallel programming experience based on NUMA-awareness.
The realization of such a system faces two key problems:
(i)~how to develop a scale-free parallel programming framework that scales efficiently across NUMA domains; (ii)~how to efficiently apply graph partitioning in order to create separate and largely independent work items that can be distributed among threads.

Simulation of Distributed Contact in String Instruments: a Modal Expansion Approach

Impactive contact between a vibrating string and a barrier is a strongly nonlinear phenomenon that presents several challenges in the design of numerical models for simulation and sound synthesis of musical string instruments. These are addressed here by applying Hamiltonian methods to incorporate distributed contact forces into a modal framework for discrete-time simulation of the dynamics of a stiff, damped string. The resulting algorithms have spectral accuracy, are unconditionally stable, and require solving a multivariate nonlinear equation that is guaranteed to have a unique solution. Exemplifying results are presented and discussed in terms of accuracy, convergence, and spurious high-frequency oscillations.