The tandem duplicator phenotype as a distinct genomic configuration in cancer.

Next-generation sequencing studies have revealed genome-wide structural variation patterns in cancer, such as chromothripsis and chromoplexy, that do not engage a single discernable driver mutation, and whose clinical relevance is unclear. We devised a robust genomic metric able to identify cancers with a chromotype called tandem duplicator phenotype (TDP) characterized by frequent and distributed tandem duplications (TDs). Enriched only in triple-negative breast cancer (TNBC) and in ovarian, endometrial, and liver cancers, TDP tumors conjointly exhibit tumor protein p53 (TP53) mutations, disruption of breast cancer 1 (BRCA1), and increased expression of DNA replication genes pointing at rereplication in a defective checkpoint environment as a plausible causal mechanism.

Functional chromatin features are associated with structural mutations in cancer.

Background: Structural mutations (SMs) play a major role in cancer development. In some cancers, such as breast and ovarian, DNA double-strand breaks (DSBs) occur more frequently in transcribed regions, while in other cancer types such as prostate, there is a consistent depletion of breakpoints in transcribed regions. Despite such regularity, little is understood about the mechanisms driving these effects.

Scotty: a web tool for designing RNA-Seq experiments to measure differential gene expression.

Motivation: A common question arises at the beginning of every experiment where RNA-Seq is used to detect differential gene expression between two conditions: How many reads should we sequence?

Results: Scotty is an interactive web-based application that assists biologists to design an experiment with an appropriate sample size and read depth to satisfy the user-defined experimental objectives. This design can be based on data available from either pilot samples or publicly available datasets.

Availability: Scotty can be freely accessed on the web at http://euler.

Copy Number Variation detection from 1000 Genomes Project exon capture sequencing data.

Background: DNA capture technologies combined with high-throughput sequencing now enable cost-effective, deep-coverage, targeted sequencing of complete exomes. This is well suited for SNP discovery and genotyping. However there has been little attention devoted to Copy Number Variation (CNV) detection from exome capture datasets despite the potentially high impact of CNVs in exonic regions on protein function.

Mechanisms of fractionated electrograms formation in the posterior left atrium during paroxysmal atrial fibrillation in humans.

Objectives: The aim of this paper was to study mechanisms of formation of fractionated electrograms on the posterior left atrial wall (PLAW) in human paroxysmal atrial fibrillation (AF).

Background: The mechanisms responsible for complex fractionated atrial electrogram formation during AF are poorly understood.

Methods: In 24 patients, we induced sustained AF by pacing from a pulmonary vein.

Specific residues of the cytoplasmic domains of cardiac inward rectifier potassium channels are effective antifibrillatory targets.

Atrial and ventricular tachyarrhythmias can be perpetuated by up-regulation of inward rectifier potassium channels. Thus, it may be beneficial to block inward rectifier channels under conditions in which their function becomes arrhythmogenic (e.g.

Complex fractionated atrial electrograms: properties of time-domain versus frequency-domain methods.

Background: Complex fractionated atrial electrograms (CFAEs) are thought to identify high-frequency electrical sources and have become an important target for radiofrequency ablation of atrial fibrillation (AF). Methods used to identify CFAEs and locate suitable ablation sites usually depend on subjective analysis of the electrograms but may also involve objective, computer-based paradigms through either time- or frequency-domain approaches.

Methods: We generated a set of simulated test electrograms, which were defined by a combination of a basic cycle length, phase-resetting noise, and phase-preserving noise, accounting for far-field effects.

A single-cell model of phase-driven control of ventricular fibrillation frequency.

The mechanisms controlling the rotation frequency of functional reentry in ventricular fibrillation (VF) are poorly understood. It has been previously shown that Ba2+ at concentrations up to 50 mumol/L slows the rotation frequency in the intact guinea pig (GP) heart, suggesting a role of the inward rectifier current (I(K1)) in the mechanism governing the VF response to Ba2+. Given that other biological (e.

Adenoviral expression of IKs contributes to wavebreak and fibrillatory conduction in neonatal rat ventricular cardiomyocyte monolayers.

Previous studies have shown that the gating kinetics of the slow component of the delayed rectifier K(+) current (I(Ks)) contribute to postrepolarization refractoriness in isolated cardiomyocytes. However, the impact of such kinetics on arrhythmogenesis remains unknown. We surmised that expression of I(Ks) in rat cardiomyocyte monolayers contributes to wavebreak formation and facilitates fibrillatory conduction by promoting postrepolarization refractoriness.