Slingshot: cell lineage and pseudotime inference for single-cell transcriptomics.

BackgroundSingle-cell transcriptomics allows researchers to investigate complex communities of heterogeneous cells. It can be applied to stem cells and their descendants in order to chart the progression from multipotent progenitors to fully differentiated cells. While a variety of statistical and computational methods have been proposed for inferring cell lineages, the problem of accurately characterizing multiple branching lineages remains difficult to solve.ResultsWe introduce Slingshot, a novel method for inferring cell lineages and pseudotimes from single-cell gene expression data. In previously published datasets, Slingshot correctly identifies the biological signal for one to three branching trajectories. Additionally, our simulation study shows that Slingshot infers more accurate pseudotimes than other leading methods.ConclusionsSlingshot is a uniquely robust and flexible tool which combines the highly stable techniques necessary for noisy single-cell data with the ability to identify multiple trajectories. Accurate lineage inference is a critical step in the identification of dynamic temporal gene expression

Third ventriculostomy vs ventriculoperitoneal shunt in pediatric obstructive hydrocephalus: results from a Swiss series and literature review

Introduction: Few series compare endoscopic third ventriculostomies (ETV) and ventriculoperitoneal shunts (VPS). To avoid the complications after a shunt insertion, there is an increased tendency to perform a third ventriculostomy. We reviewed all pediatric patients operated in the French-speaking part of Switzerland for a newly diagnosed obstructive hydrocephalus since 1992 and compared the outcome of patients who benefited from ETV to the outcome of patients who benefited from VPS. There were 24 ETV and 31 VPS. Discussion: At 5years of follow-up, the failure rate of ETV was 26%, as compared to 42% for the VPS group. This trend is also found in the pediatric series published since 1990 (27 peer-reviewed articles analyzed). Conclusion: In accordance to this trend, although a statistical difference cannot be assessed, we believe that ETV should be the procedure of choice in pediatric obstructive hydrocephalu

Supervised Detection of Regulatory Motifs in DNA Sequences

Identification of transcription factor binding sites (regulatory motifs) is a major interest in contemporary biology. We propose a new likelihood based method, COMODE, for identifying structural motifs in DNA sequences. Commonly used methods (e.g. MEME, Gibbs sampler) model binding sites as families of sequences described by a position weight matrix (PWM) and identify PWMs that maximize the likelihood of observed sequence data under a simple multinomial mixture model. This model assumes that the positions of the PWM correspond to independent multinomial distributions with four cell probabilities. We address supervising the search for DNA binding sites using the information derived from structural characteristics of protein-DNA interactions. We extend the simple multinomial mixture model by incorporating constraints on the information content profiles or on specific parameters of the motif PWMs. The parameters of this extended model are estimated by maximum likelihood using a nonlinear constraint optimization method. Likelihood-based cross-validation is used to select model parameters such as motif width and constraint type. The performance of COMODE is compared with existing motif detection methods on simulated data that incorporate real motif examples from Saccharomyces cerevisiae. The proposed method is especially effective when the motif of interest appears as a weak signal in the data. Some of the transcription factor binding data of Lee et al. (2002) were also analyzed using COMODE and biologically verified sites were identified

Quantitative description and local structures of trivalent metal ions Eu(III) and Cm(III) complexed with polyacrylic acid

The trivalent metal ion (M(III) = Cm, Eu)/polyacrylic acid (PAA) system was studied in the pH range between 3 and 5.5 for a molar PAA-to-metal ratio above 1. The interaction was studied for a wide range of PAA (0.05 mg L−1–50 g L−1) and metal ion concentrations (2×10−9–10−3 M). This work aimed at 3 goals (i) to determine the stoichiometry of M(III)–PAA complexes, (ii) to determine the number of complexed species and the local environment of the metal ion, and (iii) to quantify the reaction processes. Asymmetric flow-field-flow fractionation (AsFlFFF) coupled to ICP-MS evidenced that size distributions of Eu–PAA complexes and PAA were identical, suggesting that Eu bound to only one PAA chain. Time-resolved laser fluorescence spectroscopy (TRLFS) measurements performed with Eu and Cm showed a continuous shift of the spectra with increasing pH. The environment of complexed metal ions obviously changes with pH. Most probably, spectral variations arose from conformational changes within the M(III)–PAA complex due to pH variation. Complexation data describing the distribution of complexed and free metal ion were measured with Cm by TRLFS. They could be quantitatively described in the whole pH-range studied by considering the existence of only a single complexed species. This indicates that the slight changes in M(III) speciation with pH observed at the molecular level do not significantly affect the intrinsic binding constant. The interaction constant obtained from the modelling must be considered as a mean interaction constant

A note on spin-s duality

Duality is investigated for higher spin ($s \geq 2$), free, massless, bosonic gauge fields. We show how the dual formulations can be derived from a common "parent", first-order action. This goes beyond most of the previous treatments where higher-spin duality was investigated at the level of the equations of motion only. In D=4 spacetime dimensions, the dual theories turn out to be described by the same Pauli-Fierz (s=2) or Fronsdal ($s \geq 3$) action (as it is the case for spin 1). In the particular s=2 D=5 case, the Pauli-Fierz action and the Curtright action are shown to be related through duality. A crucial ingredient of the analysis is given by the first-order, gauge-like, reformulation of higher spin theories due to Vasiliev.Comment: Minor corrections, reference adde

MELODIE: A whole-farm model to study the dynamics of nutrients in dairy and pig farms with crops

In regions of intensive pig and dairy farming, nutrient losses to the environment at farm level are a source of concern for water and air quality. Dynamic models are useful tools to evaluate the effects of production strategies on nutrient flows and losses to the environment. This paper presents the development of a new whole-farm model upscaling dynamic models developed at the field or animal scale. The model, called MELODIE, is based on an original structure with interacting biotechnical and decisional modules. Indeed, it is supported by an ontology of production systems and the associated programming platform DIESE. The biotechnical module simulates the nutrient flows in the different animal, soil and crops and manure sub-models. The decision module relies on an annual optimization of cropping and spreading allocation plans, and on the flexible execution of activity plans for each simulated year. These plans are examined every day by an operational management sub-model and their application is context dependent. As a result, MELODIE dynamically simulates the flows of carbon, nitrogen, phosphorus, copper, zinc and water within the whole farm over the short and long-term considering both the farming system and its adaptation to climatic conditions. Therefore, it is possible to study both the spatial and temporal heterogeneity of the environmental risks, and to test changes of practices and innovative scenarios. This is illustrated with one example of simulation plan on dairy farms to interpret the Nitrogen farm-gate budget indicator. It shows that this indicator is able to reflect small differences in Nitrogen losses between different systems, but it can only be interpreted using a mobile average, not on a yearly basis. This example illustrates how MELODIE could be used to study the dynamic behaviour of the system and the dynamic of nutrient flows. Finally, MELODIE can also be used for comprehensive multi-criterion assessments, and it also constitutes a generic and evolving framework for virtual experimentation on animal farming systems. (Résumé d'auteur