How to identify pathogenic mutations among all those variations: Variant annotation and filtration in the genome sequencing era

High-throughput sequencing technologies have become fundamental for the identification of disease-causing mutations in human genetic diseases both in research and clinical testing contexts. The cumulative number of genes linked to rare diseases is now close to 3,500 with more than 1,000 genes identified between 2010 and 2014 because of the early adoption of Exome Sequencing technologies. However, despite these encouraging figures, the success rate of clinical exome diagnosis remains low due to several factors including wrong variant annotation and nonoptimal filtration practices, which may lead to misinterpretation of disease-causing mutations. In this review, we describe the critical steps of variant annotation and filtration processes to highlight a handful of potential disease-causing mutations for downstream analysis. We report the key annotation elements to gather at multiple levels for each mutation, and which systems are designed to help in collecting this mandatory information. We describe the filtration options, their efficiency, and limits and provide a generic filtration workflow and highlight potential pitfalls through a use case

PulsarX: a new pulsar searching package -I. A high performance folding program for pulsar surveys

Pulsar surveys with modern radio telescopes are becoming increasingly computationally demanding. This is particularly true for wide field-of-view pulsar surveys with radio interferometers, and those conducted in real or quasi-real time. These demands result in data analysis bottlenecks that can limit the parameter space covered by the surveys and diminish their scientific return. In this paper, we address the computational challenge of `candidate folding' in pulsar searching, presenting a novel, efficient approach designed to optimise the simultaneous folding of large numbers of pulsar candidates. We provide a complete folding pipeline appropriate for large-scale pulsar surveys including radio frequency interference (RFI) mitigation, dedispersion, folding and parameter optimization. By leveraging the Fast Discrete Dispersion Measure Transform (FDMT) algorithm proposed by Zackay et al. (2017), we have developed an optimized, and cache-friendly implementation that we term the pruned FDMT (pFDMT). The pFDMT approach efficiently reuses intermediate processing results and prunes the unused computation paths, resulting in a significant reduction in arithmetic operations. In addition, we propose a novel folding algorithm based on the Tikhonov-regularised least squares method (TLSM) that can improve the time resolution of the pulsar profile. We present the performance of its real-world application as an integral part of two major pulsar search projects conducted with the MeerKAT telescope: the MPIfR-MeerKAT Galactic Plane Survey (MMGPS) and the Transients and Pulsars with MeerKAT (TRAPUM) project. In our processing, for approximately 500 candidates, the theoretical number of dedispersion operations can be reduced by a factor of around 50 when compared to brute-force dedispersion, which scales with the number of candidates.Comment: Accepted for publication in A&

High-precision timing of 42 millisecond pulsars with the European Pulsar Timing Array

We report on the high-precision timing of 42 radio millisecond pulsars (MSPs) observed by the European Pulsar Timing Array (EPTA). This EPTA Data Release 1.0 extends up to mid-2014 and baselines range from 7–18 yr. It forms the basis for the stochastic gravitational-wave background, anisotropic background, and continuous-wave limits recently presented by the EPTA elsewhere. The Bayesian timing analysis performed with temponest yields the detection of several new parameters: seven parallaxes, nine proper motions and, in the case of six binary pulsars, an apparent change of the semimajor axis. We find the NE2001 Galactic electron density model to be a better match to our parallax distances (after correction from the Lutz–Kelker bias) than the M2 and M3 models by Schnitzeler. However, we measure an average uncertainty of 80 per cent (fractional) for NE2001, three times larger than what is typically assumed in the literature. We revisit the transverse velocity distribution for a set of 19 isolated and 57 binary MSPs and find no statistical difference between these two populations. We detect Shapiro delay in the timing residuals of PSRs J1600−3053 and J1918−0642, implying pulsar and companion masses m_p=1.22^(+0.5)_(−0.35) M_⊙, m_c=0.21^(+0.06)_(−0.04) M_⊙ and m_p=1.25^(+0.6)_(−0.4) M_⊙, m_c=0.23^(+0.07)_(−0.05) M_⊙, respectively. Finally, we use the measurement of the orbital period derivative to set a stringent constraint on the distance to PSRs J1012+5307 and J1909−3744, and set limits on the longitude of ascending node through the search of the annual-orbital parallax for PSRs J1600−3053 and J1909−3744

Avances en el conocimiento de los viroides como patógenos de frutales de hoja caduca.

Se ha demostrado que dos enfermedades de frutales de hoja caduca, el mosaico latente del melocotonero (PIM) y los chancros pustulosos del peral (PBC), hasta ahora atribuidas a virus, están realmente producidas por viroides. El PLM es una enfermedad grave, que se transmite por pulgones (al menos por Myzus persicae), que afecta a un gran número de las variedades americanas de melocotonero que se cultivan en España y que, en cambio, no se ha encontrado hasta ahora en variedades españolas. El PBC no es una enfermedad grave, ya que es latente en la mayoría de variedades de peral, pero el descubrimiento de su etiología viroidal podría facilitar el estudio de otras enfermedades similares de peral, mucho más graves, ya que afectan de forma específica a variedades importantes. Un tercer viroide, el del enanismo del lúpulo, ha sido encontrado en variedades españolas de melocotonero y albaricoquero, aunque no ha sido asociado hasta ahora a ninguna enfermedad

Amélioration de la productivité des brebis berrichonnes du cher par croisement. III. – Performances de reproduction des trois premières genérations de brebis croisées entre les races berrichonne du cher et romanov

International audienc

The Discovery of Six Recycled Pulsars from the Arecibo 327-MHz Drift-Scan Pulsar Survey

Recycled pulsars are old ($\gtrsim10^{8}$ yr) neutron stars that are descendants from close, interacting stellar systems. In order to understand their evolution and population, we must find and study the largest number possible of recycled pulsars in a way that is as unbiased as possible. In this work, we present the discovery and timing solutions of five recycled pulsars in binary systems (PSRs J0509$+$0856, J0709$+$0458, J0732$+$2314, J0824$+$0028, J2204$+$2700) and one isolated millisecond pulsar (PSR J0154$+$1833). These were found in data from the Arecibo 327-MHz Drift-Scan Pulsar Survey (AO327). All these pulsars have a low dispersion measure (DM) ($\lesssim 45 \, \rm{pc}\, cm^{-3}$), and have a DM-determined distance of $\lesssim$ 3 kpc. Their timing solutions, have data spans ranging from 1 to $\sim$ 7 years, include precise estimates of their spin and astrometric parameters, and for the binaries, precise estimates of their Keplerian binary parameters. Their orbital periods range from about 4 to 815 days and the minimum companion masses (assuming a pulsar mass of 1.4 $\rm{M_{\odot}}$) range from $\sim$ 0.06--1.11 $\rm{M_{\odot}}$. For two of the binaries we detect post-Keplerian parameters; in the case of PSR~J0709$+$0458 we measure the component masses but with a low precision, in the not too distant future the measurement of the rate of advance of periastron and the Shapiro delay will allow very precise mass measurements for this system. Like several other systems found in the AO327 data, PSRs J0509$+$0854, J0709$+$0458 and J0732$+$2314 are now part of the NANOGrav timing array for gravitational wave detection