Transposase-Accessible Chromatin followed by sequencing (ATAC-seq) is a simple protocol for detection of open chromatin. Computational footprinting, the search for regions with depletion of cleavage ...events due to transcription factor binding, is poorly understood for ATAC-seq. We propose the first footprinting method considering ATAC-seq protocol artifacts. HINT-ATAC uses a position dependency model to learn the cleavage preferences of the transposase. We observe strand-specific cleavage patterns around transcription factor binding sites, which are determined by local nucleosome architecture. By incorporating all these biases, HINT-ATAC is able to significantly outperform competing methods in the prediction of transcription factor binding sites with footprints.
Motivation: There is a strong demand in the genomic community to develop effective algorithms to reliably identify genomic variants. Indel detection using next-gen data is difficult and ...identification of long structural variations is extremely challenging. Results: We present Pindel, a pattern growth approach, to detect breakpoints of large deletions and medium-sized insertions from paired-end short reads. We use both simulated reads and real data to demonstrate the efficiency of the computer program and accuracy of the results. Availability: The binary code and a short user manual can be freely downloaded from http://www.ebi.ac.uk/∼kye/pindel/. Contact: k.ye@lumc.nl; zn1@sanger.ac.uk
Objective
Psychological distress is common in cancer patients, and awareness of its indicators is essential. We aimed to assess the prevalence of psychological distress and to identify problems ...indicative of high distress.
Methods
We used the distress thermometer (DT) and its 34‐item problem list to measure psychological distress in 3724 cancer patients (mean age 58 years; 57% women) across major tumor entities, enrolled in an epidemiological multicenter study. To identify distress‐related problems, we conducted monothetic analyses.
Results
We found high levels of psychological distress (DT ≥ 5) in 52% of patients. The most prevalent problems were fatigue (56%), sleep problems (51%), and problems getting around (47%). Sadness, fatigue, and sleep problems were most strongly associated with the presence of other problems. High distress was present in 81.4% of patients reporting all 3 of these problems (DT M = 6.4). When analyzing only the subset of physical problems, fatigue, problems getting around, and indigestion showed the strongest association with the remaining problems and 76.3% of patients with all 3 problems were highly distressed (DT M = 6.1).
Conclusions
Our results show a high prevalence of psychological distress in cancer patients, as well as a set of problems that indicate the likely presence of other problems and high distress and can help clinicians identify distressed patients even if no routine distress screening is available.
Identification and characterization of cancer subtypes are important areas of research that are based on the integrated analysis of multiple heterogeneous genomics datasets. Since there are no tools ...supporting this process, much of this work is done using ad‐hoc scripts and static plots, which is inefficient and limits visual exploration of the data. To address this, we have developed StratomeX, an integrative visualization tool that allows investigators to explore the relationships of candidate subtypes across multiple genomic data types such as gene expression, DNA methylation, or copy number data. StratomeX represents datasets as columns and subtypes as bricks in these columns. Ribbons between the columns connect bricks to show subtype relationships across datasets. Drill‐down features enable detailed exploration. StratomeX provides insights into the functional and clinical implications of candidate subtypes by employing small multiples, which allow investigators to assess the effect of subtypes on molecular pathways or outcomes such as patient survival. As the configuration of viewing parameters in such a multi‐dataset, multi‐view scenario is complex, we propose a meta visualization and configuration interface for dataset dependencies and data‐view relationships. StratomeX is developed in close collaboration with domain experts. We describe case studies that illustrate how investigators used the tool to explore subtypes in large datasets and demonstrate how they efficiently replicated findings from the literature and gained new insights into the data.
Abstract
Landslides modify the natural landscape and cause fatalities and property damage worldwide. Quantifying landslide dynamics is challenging due to the stochastic nature of the environment. ...With its large area of ~1 km
2
and perennial motions at ~10–20 mm per day, the Slumgullion landslide in Colorado, USA, represents an ideal natural laboratory to better understand landslide behavior. Here, we use hybrid remote sensing data and methods to recover the four-dimensional surface motions during 2011–2018. We refine the boundaries of an area of ~0.35 km
2
below the crest of the prehistoric landslide. We construct a mechanical framework to quantify the rheology, subsurface channel geometry, mass flow rate, and spatiotemporally dependent pore-water pressure feedback through a joint analysis of displacement and hydrometeorological measurements from ground, air and space. Our study demonstrates the importance of remotely characterizing often inaccessible, dangerous slopes to better understand landslides and other quasi-static mass fluxes in natural and industrial environments, which will ultimately help reduce associated hazards.
A second order differential equation for the energy dissipation rate of turbulence is presented. The derivation procedure is explained. The obtained governing equation is a Euler equation, which ...integration naturally conduces to power laws for the energy dissipation rate as a function of the wavenumber, a result that is extended to the energy spectrum of turbulence. Power laws are obtained for the cases of two equal and two different real roots. For the case of two conjugate complex roots, the solution is a sum of sine and cosine functions of the normal logarithm of the wavenumber. The differential equation accrues from a more basic equation obtained through thermodynamic-type steps that joint part of already consolidated empirical and semi-empirical information on turbulence existing in the literature, and is formally analogue to the Thermodynamics equation of thermal radiation. It is also shown that parameters of turbulence like length and velocity scales may be related to this formulation.
Abstract
Aims
The association between air temperature and mortality has been shown to vary over time, but evidence of temporal changes in the risk of myocardial infarction (MI) is lacking. We aimed ...to estimate the temporal variations in the association between short-term exposures to air temperature and MI in the area of Augsburg, Germany.
Methods and results
Over a 28-years period from 1987 to 2014, a total of 27 310 cases of MI and coronary deaths were recorded. Daily meteorological parameters were measured in the study area. A time-stratified case-crossover analysis with a distributed lag non-linear model was used to estimate the risk of MI associated with air temperature. Subgroup analyses were performed to identify subpopulations with changing susceptibility to air temperature. Results showed a non-significant decline in cold-related MI risks. Heat-related MI relative risk significantly increased from 0.93 95% confidence interval (CI): 0.78–1.12 in 1987–2000 to 1.14 (95% CI: 1.00–1.29) in 2001–14. The same trend was also observed for recurrent and non-ST-segment elevation MI events. This increasing population susceptibility to heat was more evident in patients with diabetes mellitus and hyperlipidaemia. Future studies using multicentre MI registries at different climatic, demographic, and socioeconomic settings are warranted to confirm our findings.
Conclusion
We found evidence of rising population susceptibility to heat-related MI risk from 1987 to 2014, suggesting that exposure to heat should be considered as an environmental trigger of MI, especially under a warming climate.
We discuss a renewal process in which successive events are separated by scale-free waiting time periods. Among other ubiquitous long-time properties, this process exhibits aging: events counted ...initially in a time interval 0,t statistically strongly differ from those observed at later times ta,ta+t . The versatility of renewal theory is owed to its abstract formulation. Renewals can be interpreted as steps of a random walk, switching events in two-state models, domain crossings of a random motion, etc. In complex, disordered media, processes with scale-free waiting times play a particularly prominent role. We set up a unified analytical foundation for such anomalous dynamics by discussing in detail the distribution of the aging renewal process. We analyze its half-discrete, half-continuous nature and study its aging time evolution. These results are readily used to discuss a scale-free anomalous diffusion process, the continuous-time random walk. By this, we not only shed light on the profound origins of its characteristic features, such as weak ergodicity breaking, along the way, we also add an extended discussion on aging effects. In particular, we find that the aging behavior of time and ensemble averages is conceptually very distinct, but their time scaling is identical at high ages. Finally, we show how more complex motion models are readily constructed on the basis of aging renewal dynamics.
We study time averages of single particle trajectories in scale-free anomalous diffusion processes, in which the measurement starts at some time t(a)>0 after initiation of the process at t=0. Using ...aging renewal theory, we show that for such nonstationary processes a large class of observables are affected by a unique aging function, which is independent of boundary conditions or the external forces. Moreover, we discuss the implications of aging induced population splitting: with growing age t(a) of the process, an increasing fraction of particles remains motionless in a measurement of fixed duration. Consequences for single biomolecule tracking in live cells are discussed.
Endothelial cells play a critical role in the adaptation of tissues to injury. Tissue ischemia induced by infarction leads to profound changes in endothelial cell functions and can induce transition ...to a mesenchymal state. Here we explore the kinetics and individual cellular responses of endothelial cells after myocardial infarction by using single cell RNA sequencing. This study demonstrates a time dependent switch in endothelial cell proliferation and inflammation associated with transient changes in metabolic gene signatures. Trajectory analysis reveals that the majority of endothelial cells 3 to 7 days after myocardial infarction acquire a transient state, characterized by mesenchymal gene expression, which returns to baseline 14 days after injury. Lineage tracing, using the Cdh5-CreERT2;mT/mG mice followed by single cell RNA sequencing, confirms the transient mesenchymal transition and reveals additional hypoxic and inflammatory signatures of endothelial cells during early and late states after injury. These data suggest that endothelial cells undergo a transient mes-enchymal activation concomitant with a metabolic adaptation within the first days after myocardial infarction but do not acquire a long-term mesenchymal fate. This mesenchymal activation may facilitate endothelial cell migration and clonal expansion to regenerate the vascular network.
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