Robust Functional Supervised Classification for Time Series

We propose using the integrated periodogram to classify time series. The method assigns a new time series to the group that minimizes the distance between the series integrated periodogram and the group mean of integrated periodograms. Local computation of these periodograms allows the application of this approach to nonstationary time series. Since the integrated periodograms are curves, we apply functional data depth-based techniques to make the classification robust, which is a clear advantage over other competitive procedures. The method provides small error rates for both simulated and real data. It improves existing approaches and presents good computational behavior.     

Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia

Chronic lymphocytic leukaemia (CLL), the most frequent leukaemia in adults in Western countries, is a heterogeneous disease with variable clinical presentation and evolution. Two major molecular subtypes can be distinguished, characterized respectively by a high or low number of somatic hypermutations in the variable region of immunoglobulin genes. The molecular changes leading to the pathogenesis of the disease are still poorly understood. Here we performed whole-genome sequencing of four cases of CLL and identified 46 somatic mutations that potentially affect gene function. Further analysis of these mutations in 363 patients with CLL identified four genes that are recurrently mutated: notch 1 (NOTCH1), exportin 1 (XPO1), myeloid differentiation primary response gene 88 (MYD88) and kelch-like 6 (KLHL6). Mutations in MYD88 and KLHL6 are predominant in cases of CLL with mutated immunoglobulin genes, whereas NOTCH1 and XPO1 mutations are mainly detected in patients with unmutated immunoglobulins. The patterns of somatic mutation, supported by functional and clinical analyses, strongly indicate that the recurrent NOTCH1, MYD88 and XPO1 mutations are oncogenic changes that contribute to the clinical evolution of the disease. To our knowledge, this is the first comprehensive analysis of CLL combining whole-genome sequencing with clinical characteristics and clinical outcomes. It highlights the usefulness of this approach for the identification of clinically relevant mutations in cancer.     

South American SLR stations monitoring ground displacement caused by the M8.8 Chilean earthquake of 2010

The M8.8 Chilean earthquake of February 27, 2010 caused a large surface displacement near its epicenter. Satellite Laser Ranging (SLR) station 7405, cooperatively operated by Germany and Chile about 130 km from the epicenter was affected by the earthquake. Another SLR station, No. 7406, operated jointly by the National Astronomical Observatories of the Chinese Academy of Sciences and San Juan University of Argentina, was about 600 km from the epicenter. Combining the observations of these two SLR stations with global SLR station observations, we calculate the geocentric coordinates of the two stations based on ITRF2000. The results show that the coordinates of the two stations have changed by varying degrees. SLR-7405 moved substantially towards the southwest with displacements of about 3.11, 0.52 and 0.49 m in X, Y, Z directions; the corresponding displacements for SLR-7406 are about 0.02, 0.03 and 0.02 m. This solution, as an independent result derived from SLR observations, could provide an essential external check for other positioning techniques such as GPS.     

The heparin-binding haemagglutinin of M. tuberculosis is required for extrapulmonary dissemination.

Tuberculosis remains the world's leading cause of death due to a single infectious agent, Mycobacterium tuberculosis, with 3 million deaths and 10 million new cases per year. The infection initiates in the lungs and can then spread rapidly to other tissues. The availability of the entire M. tuberculosis genome sequence and advances in gene disruption technologies have led to the identification of several mycobacterial determinants involved in virulence. However, no virulence factor specifically involved in the extrapulmonary dissemination of M. tuberculosis has been identified to date. Here we show that the disruption of the M. tuberculosis or Mycobacterium bovis Bacille Calmette-Guérin (BCG) hbhA gene encoding the heparin-binding haemagglutinin adhesin (HBHA) markedly affects mycobacterial interactions with epithelial cells, but not with macrophage-like cells. When nasally administered to mice, the mutant strains were severely impaired in spleen colonization, but not in lung colonization. Coating wild-type mycobacteria with anti-HBHA antibodies also impaired dissemination after intranasal infection. These results provide evidence that adhesins such as HBHA are required for extrapulmonary dissemination, and that interactions with non-phagocytic cells have an important role in the pathogenesis of tuberculosis. They also suggest that antibody responses to HBHA may add to immune protection against tuberculosis.     

Theoretical biology: comparing models of species abundance

Ecologists are struggling to explain how so many tropical tree species can coexist in tropical forests, and several empirical studies have demonstrated that negative density dependence is an important mechanism of tree-species coexistence. Volkov et al. compare a model incorporating negative density dependence with a dispersal-limited neutral model and claim that each predicts six empirical species-abundance distributions of tropical-tree communities equally well. However, we show here that their main conclusion is premature: when the two models are compared in an improved analysis, we find that the dispersal-limited model outcompetes the density-dependent model in all six cases. Hence, although density dependence is certainly an important diversity-maintaining mechanism, our improved approach indicates that the dispersal-limited model provides a more parsimonious explanation of empirical species-abundance distributions.     

A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes

We report that a single-nucleotide polymorphism (SNP) in the gene (PTPN22) encoding the lymphoid protein tyrosine phosphatase (LYP), a suppressor of T-cell activation, is associated with type 1 diabetes mellitus (T1D). The variants encoded by the two alleles, 1858C and 1858T, differ in a crucial amino acid residue involved in association of LYP with the negative regulatory kinase Csk. Unlike the variant encoded by the more common allele 1858C, the variant associated with T1D does not bind Csk.