Differential expression analysis for sequence count data

*Motivation:* High-throughput nucleotide sequencing provides quantitative readouts in assays for RNA expression (RNA-Seq), protein-DNA binding (ChIP-Seq) or cell counting (barcode sequencing). Statistical inference of differential signal in such data requires estimation of their variability throughout the dynamic range. When the number of replicates is small, error modelling is needed to achieve statistical power.

*Results:* We propose an error model that uses the negative binomial distribution, with variance and mean linked by local regression, to model the null distribution of the count data. The method controls type-I error and provides good detection power. 

*Availability:* A free open-source R software package, _DESeq_, is available from the Bioconductor project and from "http://www-huber.embl.de/users/anders/DESeq":http://www-huber.embl.de/users/anders/DESeq

Simple and robust synchrotron and laboratory solutions for high-resolution multimodal X-ray phase-based imaging

Edge illumination X-ray phase contrast imaging techniques are capable of quantitative retrieval of differential phase, absorption and X-ray scattering. We have recently developed a series of approaches enabling high-resolution implementations, both using synchrotron radiation and laboratory-based set-ups. Three-dimensional reconstruction of absorption, phase and dark-field can be achieved with a simple rotation of the sample. All these approaches share a common trait which consists in the use of an absorber that shapes the radiation field, in order to make the phase modulations introduced by the sample detectable. This enables a well-defined and high-contrast structuring of the radiation field as well as an accurate modelling of the effects that are related to the simultaneous use of a wide range of energies. Moreover, it can also be adapted for use with detectors featuring large pixel sizes, which could be desirable when a high detection efficiency is important

Targeted Activation of Hippocampal Place Cells Drives Memory-Guided Spatial Behavior

The hippocampus is crucial for spatial navigation and episodic memory formation. Hippocampal place cells exhibit spatially selective activity within an environment and have been proposed to form the neural basis of a cognitive map of space that supports these mnemonic functions. However, the direct influence of place cell activity on spatial navigation behavior has not yet been demonstrated. Using an ‘all-optical’ combination of simultaneous two-photon calcium imaging and two-photon optogenetics, we identified and selectively activated place cells that encoded behaviorally relevant locations in a virtual reality environment. Targeted stimulation of a small number of place cells was sufficient to bias the behavior of animals during a spatial memory task, providing causal evidence that hippocampal place cells actively support spatial navigation and memory

Positive words carry less information than negative words

We show that the frequency of word use is not only determined by the word length \cite{Zipf1935} and the average information content \cite{Piantadosi2011}, but also by its emotional content. We have analyzed three established lexica of affective word usage in English, German, and Spanish, to verify that these lexica have a neutral, unbiased, emotional content. Taking into account the frequency of word usage, we find that words with a positive emotional content are more frequently used. This lends support to Pollyanna hypothesis \cite{Boucher1969} that there should be a positive bias in human expression. We also find that negative words contain more information than positive words, as the informativeness of a word increases uniformly with its valence decrease. Our findings support earlier conjectures about (i) the relation between word frequency and information content, and (ii) the impact of positive emotions on communication and social links.Comment: 16 pages, 3 figures, 3 table

The effect of prolonged monocular occlusion on latent nystagmus in the treatment of amblyopia

We recorded eye movements in 5 patients with latent nystagmus (LN) before and after 2 days of occlusion of the better eye. The slow-phase speed of the nystagmus (SPS) was in general, before occlusion, lower when the better eye fixated but, after occlusion, lower when the worse eye fixated. However, the sum of SPS during right fixation and SPS during left fixation remained constant. Oscillopsia complaints gradually disappeared during the period of occlusion. These findings indicate that the difference between the SPS during fixation with the right eye and the SPS during fixation with the left eye in LN patients is caused by a compensatory drift that decreases LN during fixation with the better eye but increases LN during fixation with the worse eye. During occlusion, this compensatory drift changes its direction and magnitude slowly over days. Hence, occlusion of the better eye in children with amblyopia and LN should be prescribed only in days per week, not in hours per day

Controlling spin pumping into superconducting Nb by proximity-induced spin-triplet Cooper pairs

Proximity-induced long-range spin-triplet supercurrents, important for the field of superconducting spintronics, are generated in superconducting/ferromagnetic heterostructures when interfacial magnetic inhomogeneities responsible for spin mixing and spin flip scattering are present. The multilayer stack Nb/Cr/Fe/Cr/Nb has been shown to support such currents when fabricated into Josephson junction devices. However, creating pure spin currents controllably in superconductors outside of the Josephson junction architecture is a bottleneck to progress. Recently, ferromagnetic resonance was proposed as a possible direction, the signature of pure supercurrent creation being an enhancement of the Gilbert damping below the superconducting critical temperature, but the necessary conditions are still poorly established. Here, we demonstrate that pumping pure spin currents into a superconductor in the presence of an external magnetic field is only possible when conditions supporting proximity-induced spin-triplet effects are satisfied. Our study is an important step forward for pure spin supercurrent creation, considerably advancing the field of superconducting spintronics

ExpressionPlot: a web-based framework for analysis of RNA-Seq and microarray gene expression data

RNA-Seq and microarray platforms have emerged as important tools for detecting changes in gene expression and RNA processing in biological samples. We present ExpressionPlot, a software package consisting of a default back end, which prepares raw sequencing or Affymetrix microarray data, and a web-based front end, which offers a biologically centered interface to browse, visualize, and compare different data sets. Download and installation instructions, a user's manual, discussion group, and a prototype are available at http://expressionplot.com/ webcite.ALS Therapy Allianc

Identifying differential exon splicing using linear models and correlation coefficients

Background: With the availability of the Affymetrix exon arrays a number of tools have been developed to enable the analysis. These however can be expensive or have several pre-installation requirements. This led us to develop an analysis workflow for analysing differential splicing using freely available software packages that are already being widely used for gene expression analysis. The workflow uses the packages in the standard installation of R and Bioconductor (BiocLite) to identify differential splicing. We use the splice index method with the LIMMA framework. The main drawback with this approach is that it relies on accurate estimates of gene expression from the probe-level data. Methods such as RMA and PLIER may misestimate when a large proportion of exons are spliced. We therefore present the novel concept of a gene correlation coefficient calculated using only the probeset expression pattern within a gene. We show that genes with lower correlation coefficients are likely to be differentially spliced.Results: The LIMMA approach was used to identify several tissue-specific transcripts and splicing events that are supported by previous experimental studies. Filtering the data is necessary, particularly removing exons and genes that are not expressed in all samples and cross-hybridising probesets, in order to reduce the false positive rate. The LIMMA approach ranked genes containing single or few differentially spliced exons much higher than genes containing several differentially spliced exons. On the other hand we found the gene correlation coefficient approach better for identifying genes with a large number of differentially spliced exons.Conclusion: We show that LIMMA can be used to identify differential exon splicing from Affymetrix exon array data. Though further work would be necessary to develop the use of correlation coefficients into a complete analysis approach, the preliminary results demonstrate their usefulness for identifying differentially spliced genes. The two approaches work complementary as they can potentially identify different subsets of genes (single/few spliced exons vs. large transcript structure differences)

Mortality and incidence of second cancers following treatment for testicular cancer

We studied 5555 seminoma patients and 3733 patients with nonseminomatous testicular cancers diagnosed in Southeast England between 1960 and 2004. For both groups survival improved over time: 10-year relative survival increased from 78% in 1960–1969 to 99% in 1990–2004 for seminomas, and from 55 to 95% for nonseminomas. In the early period mortality was still significantly increased more than 15 years after diagnosis in both groups, whereas in more recent periods the excess deaths mainly occurred in the first 5 years after diagnosis. For seminomas, there was a significant excess of cancers of the colon (standardised incidence ratio (SIR) 2.36; 95% confidence interval (CI) 1.13–4.35), soft tissue (SIR 13.64; CI 1.65–49.28) and bladder (SIR 4.28; CI 2.28–7.31) in the long term (20+ years after diagnosis), of pancreatic cancer in both the medium (10–19 years) (SIR 2.91; CI 1.26–5.73) and long term (SIR 5.48; CI 2.37–10.80), of leukaemia in both the short (0–9 years) (SIR 3.01; CI 1.44–5.54) and long term (SIR 4.48; CI 1.64–9.75), and of testis cancer in both the short (SIR 6.69; CI 4.28–9.95) and medium term (SIR 3.96; CI 1.08–10.14). For nonseminomas, significant excesses were found in the long term for cancers of the stomach (SIR 5.13; CI 1.40–13.13), rectum (SIR 4.49; CI 1.22–11.51) and pancreas (SIR 10.17: CI 3.73–22.13), and for testis cancer in the medium term (SIR 5.94; CI 2.18–12.93). Leukaemia was significantly increased in the short term (SIR 6.78; CI 2.93–13.36). The better survival observed is largely attributable to improved treatment, and the trend in reducing the toxicity of therapy should continue to reduce future health risks in testicular cancer survivors