Nearest neighbor embedding with different time delays

A nearest neighbor based selection of time delays for phase space reconstruction is proposed and compared to the standard use of time delayed mutual information. The possibility of using different time delays for consecutive dimensions is considered. A case study of numerically generated solutions of the Lorenz system is used for illustration. The effect of contamination with various levels of additive Gaussian white noise is discussed.Comment: 4 pages, 5 figures, updated to final versio

Multivariate phase space reconstruction by nearest neighbor embedding with different time delays

A recently proposed nearest neighbor based selection of time delays for phase space reconstruction is extended to multivariate time series, with an iterative selection of variables and time delays. A case study of numerically generated solutions of the x- and z coordinates of the Lorenz system, and an application to heart rate and respiration data, are used for illustration.Comment: 4 pages, 3 figure

De Novo Occurrence of a Variant in ARL3 and Apparent Autosomal Dominant Transmission of Retinitis Pigmentosa.

BackgroundRetinitis pigmentosa is a phenotype with diverse genetic causes. Due to this genetic heterogeneity, genome-wide identification and analysis of protein-altering DNA variants by exome sequencing is a powerful tool for novel variant and disease gene discovery. In this study, exome sequencing analysis was used to search for potentially causal DNA variants in a two-generation pedigree with apparent dominant retinitis pigmentosa.MethodsVariant identification and analysis of three affected members (mother and two affected offspring) was performed via exome sequencing. Parental samples of the index case were used to establish inheritance. Follow-up testing of 94 additional retinitis pigmentosa pedigrees was performed via retrospective analysis or Sanger sequencing.Results and conclusionsA total of 136 high quality coding variants in 123 genes were identified which are consistent with autosomal dominant disease. Of these, one of the strongest genetic and functional candidates is a c.269A>G (p.Tyr90Cys) variant in ARL3. Follow-up testing established that this variant occurred de novo in the index case. No additional putative causal variants in ARL3 were identified in the follow-up cohort, suggesting that if ARL3 variants can cause adRP it is an extremely rare phenomenon

Segmentation of DNA into coding and noncoding regions based on inter-STOP symbols distances

In this study we set to explore the potentialities of the inter-genomic symbols distance for finding the coding regions in DNA sequences. We use the distance between STOP symbols in the DNA sequence and a chi-square statistic to evaluate the nonhomogeneity of the three possible reading frames. The results of this exploratory study suggest that inter-STOP symbols distance has strong ability to discriminate coding regions.publishe

Influence of body weight at hatching and inclusion of oat hulls in the diet on growth performance and digestive tract traits of brown-egg laying pullets from 0 to 16 wk of age

The influence of pre-incubated weight of eggs (EW) laid by 24 wk-old brown layer breeders and the inclusion (wt:wt) of 3% oat hulls (OH) in the diet on growth performance and gastrointestinal tract (GIT) traits were studied in pullets reared under stressful conditions from hatching to 16 wk of age. The initial BW of the pullets resulting from these eggs was of 29.9 and 38.2 g for the 2 extreme groups. The stress applied consisted in using a prolonged (8 h) transport time from the hatchery to the experimental facility, reducing barn temperature at night from placement to 7 d of age, and late beak trimming of the pullets (18 d). Growth performance, pullet uniformity, and GIT traits were measured by period (0 to 5 wk, 5 to 10 wk, and 10 to 16 wk of age) and cumulatively. Data were analyzed as a completely randomized design with treatments organized as a 7 × 2 factorial, with 7 groups of pullets that differed on pre-hatched EW (47 to 54 g with 1 g difference between groups) and 2 levels of OH inclusion (0 vs. 3%). Effects of EW on the variables studied were partitioned into linear and quadratic components. The stress conditions applied affected pullet growth, with BW at 5 wk of age that were as an average 27% lower than recommended by the genetic company (269 g vs. 367 g). Neither initial EW nor OH inclusion affected any of the variables studied. In summary, EW of young breeders did not affect growth performance, BW uniformity, or GIT traits of the resulting pullets from 0 to 16 wk of age. Eggs bigger than 47 g laid by young breeders can produce high quality pullets. Pullets fed diets with 3% OH performed equally to pullets fed the control diet, suggesting that the amount of fiber can be increased during the rearing period of brown egg pullet

EWS-FLI1-mediated suppression of the RAS-antagonist Sprouty 1 (SPRY1) confers aggressiveness to Ewing sarcoma

Ewing sarcoma is characterized by chromosomal translocations fusing the EWS gene with various members of the ETS family of transcription factors, most commonly FLI1. EWS-FLI1 is an aberrant transcription factor driving Ewing sarcoma tumorigenesis by either transcriptionally inducing or repressing specific target genes. Herein, we showed that Sprouty 1 (SPRY1), which is a physiological negative feedback inhibitor downstream of fibroblast growth factor (FGF) receptors (FGFRs) and other RAS-activating receptors, is an EWS-FLI1 repressed gene. EWS-FLI1 knockdown specifically increased the expression of SPRY1, while other Sprouty family members remained unaffected. Analysis of SPRY1 expression in a panel of Ewing sarcoma cells showed that SPRY1 was not expressed in Ewing sarcoma cell lines, suggesting that it could act as a tumor suppressor gene in these cells. In agreement, induction of SPRY1 in three different Ewing sarcoma cell lines functionally impaired proliferation, clonogenic growth and migration. In addition, SPRY1 expression inhibited extracellular signal-related kinase/mitogen-activated protein kinase (MAPK) signaling induced by serum and basic FGF (bFGF). Moreover, treatment of Ewing sarcoma cells with the potent FGFR inhibitor PD-173074 reduced bFGF-induced proliferation, colony formation and in vivo tumor growth in a dose-dependent manner, thus mimicking SPRY1 activity in Ewing sarcoma cells. Although the expression of SPRY1 was low when compared with other tumors, SPRY1 was variably expressed in primary Ewing sarcoma tumors and higher expression levels were significantly associated with improved outcome in a large patient cohort. Taken together, our data indicate that EWS-FLI1-mediated repression of SPRY1 leads to unrestrained bFGF-induced cell proliferation, suggesting that targeting the FGFR/MAPK pathway can constitute a promising therapeutic approach for this devastating disease.FC-A, LG-G, JCL, AS, PG-M, SEL-P, SM and JA are supported by Asociación Pablo Ugarte and Miguelañez SA, ASION-La Hucha de Tomás, Fundación La Sonrisa de Alex and Instituto de Salud Carlos III (PI12/00816 and Spanish Cancer Network RTICC RD12/0036/0027). TGPG is supported by a grant from ‘Verein zur Förderung von Wissenschaft und Forschung an der Medizinischen Fakultät der LMU München (WiFoMed)’, the Daimler and Benz Foundation in cooperation with the Reinhard Frank Foundation, by LMU Munich’s Institutional Strategy LMUexcellent within the framework of the German Excellence Initiative, the ‘Mehr LEBEN für krebskranke Kinder—Bettina-Bräu-Stiftung’, the Walter Schulz Foundation, the Fritz Thyssen Foundation (FTH-40.15.0.030MN) and by the German Cancer Aid (DKH-111886 and DKH-70112257). The ‘Genetics and Biology of Cancers’ team (TGPG, DS and OD) is supported by grants from the Ligue Nationale Contre Le Cancer (Equipe labellisée). This work was also supported by the European PROVABES, ASSET and EEC FP7 grants. We also thank the following associations for their invaluable support: the Société Française des Cancers de l’Enfant, Courir pour Mathieu, Dans les pas du Géant, Olivier Chape, Les Bagouzamanon, Enfants et Santé and les Amis de Claire. We thank Dr S Navarro (University of Valencia, Valencia, Spain) and Dr TJ Triche (Children’s Hospital Los Angeles, Los Angeles, USA) for providing us with Ewing sarcoma cell lines A4573 and TTC-466, respectively.S

Robust lineage reconstruction from high-dimensional single-cell data

Single-cell gene expression data provide invaluable resources for systematic characterization of cellular hierarchy in multi-cellular organisms. However, cell lineage reconstruction is still often associated with significant uncertainty due to technological constraints. Such uncertainties have not been taken into account in current methods. We present ECLAIR (Ensemble Cell Lineage Analysis with Improved Robustness), a novel computational method for the statistical inference of cell lineage relationships from single-cell gene expression data. ECLAIR uses an ensemble approach to improve the robustness of lineage predictions, and provides a quantitative estimate of the uncertainty of lineage branchings. We show that the application of ECLAIR to published datasets successfully reconstructs known lineage relationships and significantly improves the robustness of predictions. ECLAIR is a powerful bioinformatics tool for single-cell data analysis. It can be used for robust lineage reconstruction with quantitative estimate of prediction accuracy