AuPairWise: A Method to Estimate RNA-Seq Replicability through Co-expression

In addition to detecting novel transcripts and higher dynamic range, a principal claim for RNA-sequencing has been greater replicability, typically measured in sample-sample correlations of gene expression levels. Through a re-analysis of ENCODE data, we show that replicability of transcript abundances will provide misleading estimates of the replicability of conditional variation in transcript abundances (i.e., most expression experiments). Heuristics which implicitly address this problem have emerged in quality control measures to obtain 'good' differential expression results. However, these methods involve strict filters such as discarding low expressing genes or using technical replicates to remove discordant transcripts, and are costly or simply ad hoc. As an alternative, we model gene-level replicability of differential activity using co-expressing genes. We find that sets of housekeeping interactions provide a sensitive means of estimating the replicability of expression changes, where the co-expressing pair can be regarded as pseudo-replicates of one another. We model the effects of noise that perturbs a gene's expression within its usual distribution of values and show that perturbing expression by only 5% within that range is readily detectable (AUROC~0.73). We have made our method available as a set of easily implemented R scripts

Dynamics of coreless vortices and rotation-induced dissipation peak in superfluid films on rotating porous substrates

We analyze dynamics of 3D coreless vortices in superfluid films covering porous substrates. The 3D vortex dynamics is derived from the 2D dynamics of the film. The motion of a 3D vortex is a sequence of jumps between neighboring substrate cells, which can be described, nevertheless, in terms of quasi-continuous motion with average vortex velocity. The vortex velocity is derived from the dissociation rate of vortex-antivortex pairs in a 2D film, which was developed in the past on the basis of the Kosterlitz-Thouless theory. The theory explains the rotation-induced dissipation peak in torsion-oscillator experiments on $^4$He films on rotating porous substrates and can be used in the analysis of other phenomena related to vortex motion in films on porous substrates.Comment: 8 pages, 3 figures submitted to Phys. Rev.

Over vlugge spraak en vluchtige sjwa’s De relatie tussen spreektempo en de duur van Nederlandse svarabhaktivocalen

This study investigates the relationship between speech tempo and the duration of epentheticschwa in Dutch. The speech materials consisted of the spontaneous speech of 160 teachers of Dutch: these speakers were equally distributed over four different regions in Belgium and the Netherlands. There were an equal number of men and women. The research focus was on 750words which contained a consonant cluster with ras the first element and a non-alveolar consonant or nas the second element. These words consisted of two or three syllables after schwa insertion (e.g., werk‘work’ > [wɛrək], werken‘to work’ > [wɛrəkən]). The speech rate of these words was calculated and the duration of any inserted schwa was measured. As predicted, the results show a clear relationship between speech rate and the duration of schwa: faster speech yields shorter schwas. Besides this general trend a statistically significant effect was found of geographical region, the number of syllables, the place of articulation of rand the second element of the consonant cluster. In addition, there was a significant interaction between speech tempo and the schwa duration in men and women: women produce shorter schwas in faster speech, while their shwas in slower speech are longer thanthose in men. As such the durational differences in schwa are more outspoken in women thanin men. This can be accounted for by the general trend that vowels are generally longer in women’s speech. The shorter schwa durations in women’s fast speech may have to do with the fact that it is easier for women to bridge articulatory distances as a result of smaller oral cavity volume

Using predictive specificity to determine when gene set analysis is biologically meaningful

Gene set analysis, which translates gene lists into enriched functions, is among the most common bioinformatic methods. Yet few would advocate taking the results at face value. Not only is there no agreement on the algorithms themselves, there is no agreement on how to benchmark them. In this paper, we evaluate the robustness and uniqueness of enrichment results as a means of assessing methods even where correctness is unknown. We show that heavily annotated ('multifunctional') genes are likely to appear in genomics study results and drive the generation of biologically non-specific enrichment results as well as highly fragile significances. By providing a means of determining where enrichment analyses report non-specific and non-robust findings, we are able to assess where we can be confident in their use. We find significant progress in recent bias correction methods for enrichment and provide our own software implementation. Our approach can be readily adapted to any pre-existing package

Transverse NMR relaxation as a probe of mesoscopic structure

Transverse NMR relaxation in a macroscopic sample is shown to be extremely sensitive to the structure of mesoscopic magnetic susceptibility variations. Such a sensitivity is proposed as a novel kind of contrast in the NMR measurements. For suspensions of arbitrary shaped paramagnetic objects, the transverse relaxation is found in the case of a small dephasing effect of an individual object. Strong relaxation rate dependence on the objects' shape agrees with experiments on whole blood. Demonstrated structure sensitivity is a generic effect that arises in NMR relaxation in porous media, biological systems, as well as in kinetics of diffusion limited reactions.Comment: 4 pages, 3 figure

Meta-Learning for Phonemic Annotation of Corpora

We apply rule induction, classifier combination and meta-learning (stacked classifiers) to the problem of bootstrapping high accuracy automatic annotation of corpora with pronunciation information. The task we address in this paper consists of generating phonemic representations reflecting the Flemish and Dutch pronunciations of a word on the basis of its orthographic representation (which in turn is based on the actual speech recordings). We compare several possible approaches to achieve the text-to-pronunciation mapping task: memory-based learning, transformation-based learning, rule induction, maximum entropy modeling, combination of classifiers in stacked learning, and stacking of meta-learners. We are interested both in optimal accuracy and in obtaining insight into the linguistic regularities involved. As far as accuracy is concerned, an already high accuracy level (93% for Celex and 86% for Fonilex at word level) for single classifiers is boosted significantly with additional error reductions of 31% and 38% respectively using combination of classifiers, and a further 5% using combination of meta-learners, bringing overall word level accuracy to 96% for the Dutch variant and 92% for the Flemish variant. We also show that the application of machine learning methods indeed leads to increased insight into the linguistic regularities determining the variation between the two pronunciation variants studied.Comment: 8 page

Ligand Similarity Complements Sequence, Physical Interaction, and Co-Expression for Gene Function Prediction

The expansion of protein-ligand annotation databases has enabled large-scale networking of proteins by ligand similarity. These ligand-based protein networks, which implicitly predict the ability of neighboring proteins to bind related ligands, may complement biologically-oriented gene networks, which are used to predict functional or disease relevance. To quantify the degree to which such ligand-based protein associations might complement functional genomic associations, including sequence similarity, physical protein-protein interactions, co-expression, and disease gene annotations, we calculated a network based on the Similarity Ensemble Approach (SEA: sea.docking.org), where protein neighbors reflect the similarity of their ligands. We also measured the similarity with functional genomic networks over a common set of 1,131 genes, and found that the networks had only small overlaps, which were significant only due to the large scale of the data. Consistent with the view that the networks contain different information, combining them substantially improved Molecular Function prediction within GO (from AUROC~0.63-0.75 for the individual data modalities to AUROC~0.8 in the aggregate). We investigated the boost in guilt-by-association gene function prediction when the networks are combined and describe underlying properties that can be further exploited

Exploiting single-cell expression to characterize co-expression replicability

BACKGROUND: Co-expression networks have been a useful tool for functional genomics, providing important clues about the cellular and biochemical mechanisms that are active in normal and disease processes. However, co-expression analysis is often treated as a black box with results being hard to trace to their basis in the data. Here, we use both published and novel single-cell RNA sequencing (RNA-seq) data to understand fundamental drivers of gene-gene connectivity and replicability in co-expression networks. RESULTS: We perform the first major analysis of single-cell co-expression, sampling from 31 individual studies. Using neighbor voting in cross-validation, we find that single-cell network connectivity is less likely to overlap with known functions than co-expression derived from bulk data, with functional variation within cell types strongly resembling that also occurring across cell types. To identify features and analysis practices that contribute to this connectivity, we perform our own single-cell RNA-seq experiment of 126 cortical interneurons in an experimental design targeted to co-expression. By assessing network replicability, semantic similarity and overall functional connectivity, we identify technical factors influencing co-expression and suggest how they can be controlled for. Many of the technical effects we identify are expression-level dependent, making expression level itself highly predictive of network topology. We show this occurs generally through re-analysis of the BrainSpan RNA-seq data. CONCLUSIONS: Technical properties of single-cell RNA-seq data create confounds in co-expression networks which can be identified and explicitly controlled for in any supervised analysis. This is useful both in improving co-expression performance and in characterizing single-cell data in generally applicable terms, permitting cross-laboratory comparison within a common framework

De svarabhaktivocaal in het Standaardnederlands: een pioniersstudie.

This paper studies the duration of epenthetic schwa in spontaneously spoken Standard Dutch. It focuses on tautosyllabic and heterosyllabic consonant clusters consisting of /r/ followed by a non-alveolar consonant(e.g. werk vs. werken). The sample consists of spontaneous speech produced by 160 teachers of Dutch, originating from different regions in Flanders and the Netherlands. The average duration of epenthetic schwa appeared to be somewhat longer in the Netherlands (46,2 ms) than in Flanders (42,9 ms). Moreover, we found a significant interaction between country and region of origin. Sex and age (as main effect) did not cause significant differences

Search for supersolidity in 4He in low-frequency sound experiments

We present results of the search for supersolid 4He using low-frequency, low-level mechanical excitation of a solid sample grown and cooled at fixed volume. We have observed low frequency non-linear resonances that constitute anomalous features. These features, which appear below about 0.8 K, are absent in 3He. The frequency, the amplitude at which the nonlinearity sets in, and the upper temperature limit of existence of these resonances depend markedly on the sample history.Comment: Submitted to the Quantum Fluids and Solids Conf. Aug. 2006 Kyot