A probabilistic model to recover individual genomes from metagenomes

Shotgun metagenomics of microbial communities reveal information about strains of relevance for applications in medicine, biotechnology and ecology. Recovering their genomes is a crucial but very challenging step due to the complexity of the underlying biological system and technical factors. Microbial communities are heterogeneous, with oftentimes hundreds of present genomes deriving from different speci

Accurate and scalable variant calling from single cell DNA sequencing data with ProSolo

Accurate single cell mutational profiles can reveal genomic cell-to-cell heterogeneity. However, sequencing libraries suitable for genotyping require whole genome amplification, which introduces allelic bias and copy errors. The resulting data violates assumptions of variant callers developed for bulk sequencing. Thus, only dedicated models accounting for amplification bias and errors can provide accurate calls. We present ProSolo for calling single nucleotide variants from multiple displacement amplified (MDA) single cell DNA sequencing data. ProSolo probabilistically models a single cell jointly with a bulk sequencing sample and integrat

Measuring Black Hole Spin using X-ray Reflection Spectroscopy

I review the current status of X-ray reflection (a.k.a. broad iron line) based black hole spin measurements. This is a powerful technique that allows us to measure robust black hole spins across the mass range, from the stellar-mass black holes in X-ray binaries to the supermassive black holes in active galactic nuclei. After describing the basic assumptions of this approach, I lay out the detailed methodology focusing on "best practices" that have been found necessary to obtain robust results. Reflecting my own biases, this review is slanted towards a discussion of supermassive black hole (SMBH) spin in active galactic nuclei (AGN). Pulling together all of the available XMM-Newton and Suzaku results from the literature that satisfy objective quality control criteria, it is clear that a large fraction of SMBHs are rapidly-spinning, although there are tentative hints of a more slowly spinning population at high (M>5*10^7Msun) and low (M<2*10^6Msun) mass. I also engage in a brief review of the spins of stellar-mass black holes in X-ray binaries. In general, reflection-based and continuum-fitting based spin measures are in agreement, although there remain two objects (GROJ1655-40 and 4U1543-475) for which that is not true. I end this review by discussing the exciting frontier of relativistic reverberation, particularly the discovery of broad iron line reverberation in XMM-Newton data for the Seyfert galaxies NGC4151, NGC7314 and MCG-5-23-16. As well as confirming the basic paradigm of relativistic disk reflection, this detection of reverberation demonstrates that future large-area X-ray observatories such as LOFT will make tremendous progress in studies of strong gravity using relativistic reverberation in AGN.Comment: 19 pages. To appear in proceedings of the ISSI-Bern workshop on "The Physics of Accretion onto Black Holes" (8-12 Oct 2012). Revised version adds a missing source to Table 1 and Fig.6 (IRAS13224-3809) and corrects the referencing of the discovery of soft lags in 1H0707-495 (which were in fact first reported in Fabian et al. 2009

Bridging the gap between stellar-mass black holes and ultraluminous X-ray sources

The X-ray spectral and timing properties of ultraluminous X-ray sources (ULXs) have many similarities with the very high state of stellar-mass black holes (power-law dominated, at accretion rates greater than the Eddington rate). On the other hand, their cool disk components, large characteristic inner-disk radii and low characteristic timescales have been interpreted as evidence of black hole masses ~ 1000 Msun (intermediate-mass black holes). Here we re-examine the physical interpretation of the cool disk model, in the context of accretion states of stellar-mass black holes. In particular, XTE J1550-564 can be considered the missing link between ULXs and stellar-mass black holes, because it exhibits a high-accretion-rate, low-disk-temperature state (ultraluminous branch). On the ultraluminous branch, the accretion rate is positively correlated with the disk truncation radius and the bolometric disk luminosity, while it is anti-correlated with the peak temperature and the frequency of quasi-periodic-oscillations. Two prototypical ULXs (NGC1313 X-1 and X-2) also seem to move along that branch. We use a phenomenological model to show how the different range of spectral and timing parameters found in the two classes of accreting black holes depends on both their masses and accretion rates. We suggest that ULXs are consistent with black hole masses ~ 50-100 Msun, moderately inefficiently accreting at ~20 times Eddington.Comment: 11 pages, accepted for publication in Astrophysics and Space Science. Based on work presented at the Fifth Stromlo Symposium, Australian National University, Dec 200

The U.K. Deep and Medium Surveys with Rosat: log N-Log S relation

We have carried out a soft X-ray survey of the sky using the ROSAT Position Sensitive Proportional Counter (PSPC) in a region of very low Galactic column density (NH = 6–9 × 1019 cm–2). The data consist of a deep > 70 ks pointing (the Deep Survey) and six pointings at lower sensitivity (13–20 ks; the Medium Survey). We detect a total of 141 sources over the 0.9 deg2 of sky area used. The faintest source detected has a flux of 3.2 × 10–15 erg cm–2 s–1 (0.5–2.0 keV). We present the source number-flux distribution, and we compare it with the distributions constructed from other ROSAT observations and from surveys carried out with X-ray instruments operating at higher energies. We estimate the contribution of the resolved sources to the soft X-ray background by direct comparison of their integrated spectrum with that of the diffuse background: 44 per cent of the extragalactic X-ray background between 0.5 and 2.0 keV is resolved directly into discrete sources whose average spectrum is steeper than that of the background. Integration of our number-flux relation to infinite flux produces a background resolved fraction of 44±565 per cent (0.5–2.0 keV). Limits on the slope of the log N–log S curve at very faint fluxes are set by the measured value of the X-ray background.KOM, ACF and RGM acknowledge the support of the Royal Society.Peer Reviewe

An overview of jets and outflows in stellar mass black holes

In this book chapter, we will briefly review the current empirical understanding of the relation between accretion state and and outflows in accreting stellar mass black holes. The focus will be on the empirical connections between X-ray states and relativistic (`radio') jets, although we are now also able to draw accretion disc winds into the picture in a systematic way. We will furthermore consider the latest attempts to measure/order jet power, and to compare it to other (potentially) measurable quantities, most importantly black hole spin.Comment: Accepted for publication in Space Science Reviews. Also to appear in the Space Sciences Series of ISSI - The Physics of Accretion on to Black Holes (Springer Publisher

Genomics and drug profiling of fatal TCF3-HLF-positive acute lymphoblastic leukemia identifies recurrent mutation patterns and therapeutic options.

TCF3-HLF-positive acute lymphoblastic leukemia (ALL) is currently incurable. Using an integrated approach, we uncovered distinct mutation, gene expression and drug response profiles in TCF3-HLF-positive and treatment-responsive TCF3-PBX1-positive ALL. We identified recurrent intragenic deletions of PAX5 or VPREB1 in constellation with the fusion of TCF3 and HLF. Moreover somatic mutations in the non-translocated allele of TCF3 and a reduction of PAX5 gene dosage in TCF3-HLF ALL suggest cooperation within a restricted genetic context. The enrichment for stem cell and myeloid features in the TCF3-HLF signature may reflect reprogramming by TCF3-HLF of a lymphoid-committed cell of origin toward a hybrid, drug-resistant hematopoietic state. Drug response profiling of matched patient-derived xenografts revealed a distinct profile for TCF3-HLF ALL with resistance to conventional chemotherapeutics but sensitivity to glucocorticoids, anthracyclines and agents in clinical development. Striking on-target sensitivity was achieved with the BCL2-specific inhibitor venetoclax (ABT-199). This integrated approach thus provides alternative treatment options for this deadly disease

The correlated optical and radio variability of BL Lacertae - WEBT data analysis 1994-2005

Since 1997, BL Lacertae has undergone a phase of high optical activity, with the occurrence of several prominent outbursts. Starting from 1999, the Whole Earth Blazar Telescope (WEBT) consortium has organized various multifrequency campaigns on this blazar, collecting tens of thousands of data points. One of the main issues in the study of this huge dataset has been the search for correlations between the optical and radio flux variations, and for possible periodicities in the light curves. The analysis of the data assembled during the first four campaigns (comprising also archival data to cover the period 1968-2003) revealed a fair optical-radio correlation in 1994-2003, with a delay of the hard radio events of ~100 days. Moreover, various statistical methods suggested the existence of a radio periodicity of ~8 years. In 2004 the WEBT started a new campaign to extend the dataset to the most recent observing seasons, in order to possibly confirm and better understand the previous results. In this campaign we have collected and assembled about 11000 new optical observations from twenty telescopes, plus near-IR and radio data at various frequencies. Here, we perform a correlation analysis on the long-term R-band and radio light curves. In general, we confirm the ~100-day delay of the hard radio events with respect to the optical ones, even if longer (~200-300 days) time lags are also found in particular periods. The radio quasi-periodicity is confirmed too, but the "period" seems to progressively lengthen from 7.4 to 9.3 years in the last three cycles. The optical and radio behaviour in the last forty years suggests a scenario where geometric effects play a major role. In particular, the alternation of enhanced and suppressed optical activity (accompanied by hard and soft radio events, respectively) ca