VeChat: correcting errors in long reads using variation graphs

Error correction is the canonical first step in long-read sequencing data analysis. Current self-correction methods, however, are affected by consensus sequence induced biases that mask true variants in haplotypes of lower frequency showing in mixed samples. Unlike consensus sequence templates, graph-based reference systems are not affected by such biases, so do not mistakenly mask true variants as errors. We present VeChat, as an approach to implement this idea: VeChat is based on variation graphs, as a popular type of data structure for pangenome reference systems. Extensive benchmarking experiments demonstrate that long reads corrected by VeChat contain 4 to 15 (Pacific Biosciences) and 1 to 10 times (Oxford Nanopore Technologies) less errors than when being corrected by state of the art approaches. Further, using VeChat prior to long-read assembly significantly improves the haplotype awareness of the assemblies. VeChat is an easy-to-use open-source tool and publicly available at https://github.com/HaploKit/vechat

Strainline: Full-length de novo viral haplotype reconstruction from noisy long reads

Haplotype-resolved de novo assembly of highly diverse virus genomes is critical in prevention, control and treatment of viral diseases. Current methods either can handle only relatively accurate short read data, or collapse haplotype-specific variations into consensus sequence. Here, we present Strainline, a novel approach to assemble viral haplotypes from noisy long reads without a reference genome. Strainline is the first approach to provide strain-resolved, full-length de novo assemblies of viral quasispecies from noisy third-generation sequencing data. Benchmarking on simulated and real datasets of varying complexity and diversity confirm this novelty and demonstrate the superiority of Strainline

phasebook: haplotype-aware de novo assembly of diploid genomes from long reads

Haplotype-aware diploid genome assembly is crucial in genomics, precision medicine, and many other disciplines. Long-read sequencing technologies have greatly improved genome assembly. However, current long-read assemblers are either reference based, so introduce biases, or fail to capture the haplotype diversity of diploid genomes. We present phasebook, a de novo approach for reconstructing the haplotypes of diploid genomes from long reads. phasebook outperforms other approaches in terms of haplotype coverage by large margins, in addition to achieving competitive performance in terms of assembly errors and assembly contiguity

OGRE: Overlap Graph-based metagenomic Read clustEring

MOTIVATION: The microbes that live in an environment can be identified from the combined genomic material, also referred to as the metagenome. Sequencing a metagenome can result in large volumes of sequencing reads. A promising approach to reduce the size of metagenomic datasets is by clustering reads into groups based on their overlaps. Clustering reads are valuable to facilitate downstream analyses, including computationally intensive strain-aware assembly. As current read clustering approaches cannot handle the large datasets arising from high-throughput metagenome sequencing, a novel read clustering approach is needed. In this article, we propose OGRE, an Overlap Graph-based Read clustEring procedure for high-throughput sequencing data, with a focus on shotgun metagenomes. RESULTS: We show that for small datasets OGRE outperforms other read binners in terms of the number of species included in a cluster, also referred to as cluster purity, and the fraction of all reads that is placed in one of the clusters. Furthermore, OGRE is able to process metagenomic datasets that are too large for other read binners into clusters with high cluster purity. CONCLUSION: OGRE is the only method that can successfully cluster reads in species-specific clusters for large metagenomic datasets without running into computation time- or memory issues. AVAILABILITY AND IMPLEMENTATION: Code is made available on Github (https://github.com/Marleen1/OGRE). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online

Normalization factors for magnetic relaxation of small particle systems in non-zero magnetic field

We critically discuss relaxation experiments in magnetic systems that can be characterized in terms of an energy barrier distribution, showing that proper normalization of the relaxation data is needed whenever curves corresponding to different temperatures are to be compared. We show how these normalization factors can be obtained from experimental data by using the $T \ln(t/\tau_0)$ scaling method without making any assumptions about the nature of the energy barrier distribution. The validity of the procedure is tested using a ferrofluid of Fe_3O_4 particles.Comment: 5 pages, 6 eps figures added in April 22, to be published in Phys. Rev. B 55 (1 April 1997

Differential Specificity of Endocrine FGF19 and FGF21 to FGFR1 and FGFR4 in Complex with KLB

Background: Recent studies suggest that betaKlotho (KLB) and endocrine FGF19 and FGF21 redirect FGFR signaling to regulation of metabolic homeostasis and suppression of obesity and diabetes. However, the identity of the predominant metabolic tissue in which a major FGFR-KLB resides that critically mediates the differential actions and metabolism effects of FGF19 and FGF21 remain unclear. Methodology/Principal Findings: We determined the receptor and tissue specificity of FGF21 in comparison to FGF19 by using direct, sensitive and quantitative binding kinetics, and downstream signal transduction and expression of early response gene upon administration of FGF19 and FGF21 in mice. We found that FGF21 binds FGFR1 with much higher affinity than FGFR4 in presence of KLB; while FGF19 binds both FGFR1 and FGFR4 in presence of KLB with comparable affinity. The interaction of FGF21 with FGFR4-KLB is very weak even at high concentration and could be negligible at physiological concentration. Both FGF19 and FGF21 but not FGF1 exhibit binding affinity to KLB. The binding of FGF1 is dependent on where FGFRs are present. Both FGF19 and FGF21 are unable to displace the FGF1 binding, and conversely FGF1 cannot displace FGF19 and FGF21 binding. These results indicate that KLB is an indispensable mediator for the binding of FGF19 and FGF21 to FGFRs that is not required for FGF1. Although FGF19 can predominantly activate the responses of the liver and to a less extent the adipose tissue, FGF21 can do so significantly only in the adipose tissue an

Searching for Long Strings in CMB Maps

Using analytical methods and Monte Carlo simulations, we analyze new statistics designed to detect isolated step-like discontinuities which are coherent over large areas of Cosmic Microwave Background (CMB) pixel maps. Such coherent temperature discontinuities are predicted by the Kaiser-Stebbins effect to form due to long cosmic strings present in our present horizon. The background of the coherent step-like seed is assumed to be a scale invariant Gaussian random field which could have been produced by a superposition of seeds on smaller scales and/or by inflationary quantum fluctuations. We find that the proposed statistics can detect the presense of a coherent discontinuity at a sensitivity level almost an order of magnitude better compared to more conventional statistics like the skewness or the kurtosis.Comment: 10 pages, 3 Figures, Use RevTe

Autoantibodies to Agrin in Myasthenia Gravis Patients

To determine if patients with myasthenia gravis (MG) have antibodies to agrin, a proteoglycan released by motor neurons and is critical for neuromuscular junction (NMJ) formation, we collected serum samples from 93 patients with MG with known status of antibodies to acetylcholine receptor (AChR), muscle specific kinase (MuSK) and lipoprotein-related 4 (LRP4) and samples from control subjects (healthy individuals and individuals with other diseases). Sera were assayed for antibodies to agrin. We found antibodies to agrin in 7 serum samples of MG patients. None of the 25 healthy controls and none of the 55 control neurological patients had agrin antibodies. Two of the four triple negative MG patients (i.e., no detectable AChR, MuSK or LRP4 antibodies, AChR-/MuSK-/LRP4-) had antibodies against agrin. In addition, agrin antibodies were detected in 5 out of 83 AChR+/MuSK-/LRP4- patients but were not found in the 6 patients with MuSK antibodies (AChR-/MuSK+/LRP4-). Sera from MG patients with agrin antibodies were able to recognize recombinant agrin in conditioned media and in transfected HEK293 cells. These sera also inhibited the agrin-induced MuSK phosphorylation and AChR clustering in muscle cells. Together, these observations indicate that agrin is another autoantigen in patients with MG and agrin autoantibodies may be pathogenic through inhibition of agrin/LRP4/MuSK signaling at the NMJ

Orbital effects of a monochromatic plane gravitational wave with ultra-low frequency incident on a gravitationally bound two-body system

We analytically compute the long-term orbital variations of a test particle orbiting a central body acted upon by an incident monochromatic plane gravitational wave. We assume that the characteristic size of the perturbed two-body system is much smaller than the wavelength of the wave. Moreover, we also suppose that the wave's frequency is much smaller than the particle's orbital one. We make neither a priori assumptions about the direction of the wavevector nor on the orbital geometry of the planet. We find that, while the semi-major axis is left unaffected, the eccentricity, the inclination, the longitude of the ascending node, the longitude of pericenter and the mean anomaly undergo non-vanishing long-term changes. They are not secular trends because of the slow modulation introduced by the tidal matrix coefficients and by the orbital elements themselves. They could be useful to indepenedently constrain the ultra-low frequency waves which may have been indirectly detected in the BICEP2 experiment. Our calculation holds, in general, for any gravitationally bound two-body system whose characteristic frequency is much larger than the frequency of the external wave. It is also valid for a generic perturbation of tidal type with constant coefficients over timescales of the order of the orbital period of the perturbed particle.Comment: LaTex2e, 24 pages, no figures, no tables. Changes suggested by the referees include