100 research outputs found

    Dynamics of mitochondrial heteroplasmy in three families investigated via a repeatable re-sequencing study

    Get PDF
    Background: Originally believed to be a rare phenomenon, heteroplasmy - the presence of more than one mitochondrial DNA (mtDNA) variant within a cell, tissue, or individual - is emerging as an important component of eukaryotic genetic diversity. Heteroplasmies can be used as genetic markers in applications ranging from forensics to cancer diagnostics. Yet the frequency of heteroplasmic alleles may vary from generation to generation due to the bottleneck occurring during oogenesis. Therefore, to understand the alterations in allele frequencies at heteroplasmic sites, it is of critical importance to investigate the dynamics of maternal mtDNA transmission. Results: Here we sequenced, at high coverage, mtDNA from blood and buccal tissues of nine individuals from three families with a total of six maternal transmission events. Using simulations and re-sequencing of clonal DNA, we devised a set of criteria for detecting polymorphic sites in heterogeneous genetic samples that is resistant to the noise originating from massively parallel sequencing technologies. Application of these criteria to nine human mtDNA samples revealed four heteroplasmic sites. Conclusions: Our results suggest that the incidence of heteroplasmy may be lower than estimated in some other recent re-sequencing studies, and that mtDNA allelic frequencies differ significantly both between tissues of the same individual and between a mother and her offspring. We designed our study in such a way that the complete analysis described here can be repeated by anyone either at our site or directly on the Amazon Cloud. Our computational pipeline can be easily modified to accommodate other applications, such as viral re-sequencing

    The Atacama Cosmology Telescope: A Measurement of the DR6 CMB Lensing Power Spectrum and its Implications for Structure Growth

    Full text link
    We present new measurements of cosmic microwave background (CMB) lensing over 94009400 sq. deg. of the sky. These lensing measurements are derived from the Atacama Cosmology Telescope (ACT) Data Release 6 (DR6) CMB dataset, which consists of five seasons of ACT CMB temperature and polarization observations. We determine the amplitude of the CMB lensing power spectrum at 2.3%2.3\% precision (43σ43\sigma significance) using a novel pipeline that minimizes sensitivity to foregrounds and to noise properties. To ensure our results are robust, we analyze an extensive set of null tests, consistency tests, and systematic error estimates and employ a blinded analysis framework. The baseline spectrum is well fit by a lensing amplitude of Alens=1.013±0.023A_{\mathrm{lens}}=1.013\pm0.023 relative to the Planck 2018 CMB power spectra best-fit Λ\LambdaCDM model and Alens=1.005±0.023A_{\mathrm{lens}}=1.005\pm0.023 relative to the ACT DR4+WMAP\text{ACT DR4} + \text{WMAP} best-fit model. From our lensing power spectrum measurement, we derive constraints on the parameter combination S8CMBLσ8(Ωm/0.3)0.25S^{\mathrm{CMBL}}_8 \equiv \sigma_8 \left({\Omega_m}/{0.3}\right)^{0.25} of S8CMBL=0.818±0.022S^{\mathrm{CMBL}}_8= 0.818\pm0.022 from ACT DR6 CMB lensing alone and S8CMBL=0.813±0.018S^{\mathrm{CMBL}}_8= 0.813\pm0.018 when combining ACT DR6 and Planck NPIPE CMB lensing power spectra. These results are in excellent agreement with Λ\LambdaCDM model constraints from Planck or ACT DR4+WMAP\text{ACT DR4} + \text{WMAP} CMB power spectrum measurements. Our lensing measurements from redshifts z0.5z\sim0.5--55 are thus fully consistent with Λ\LambdaCDM structure growth predictions based on CMB anisotropies probing primarily z1100z\sim1100. We find no evidence for a suppression of the amplitude of cosmic structure at low redshiftsComment: 45+21 pages, 50 figures. Prepared for submission to ApJ. Also see companion papers Madhavacheril et al and MacCrann et a

    The Atacama Cosmology Telescope: High-resolution component-separated maps across one-third of the sky

    Full text link
    Observations of the millimeter sky contain valuable information on a number of signals, including the blackbody cosmic microwave background (CMB), Galactic emissions, and the Compton-yy distortion due to the thermal Sunyaev-Zel'dovich (tSZ) effect. Extracting new insight into cosmological and astrophysical questions often requires combining multi-wavelength observations to spectrally isolate one component. In this work, we present a new arcminute-resolution Compton-yy map, which traces out the line-of-sight-integrated electron pressure, as well as maps of the CMB in intensity and E-mode polarization, across a third of the sky (around 13,000 sq.~deg.). We produce these through a joint analysis of data from the Atacama Cosmology Telescope (ACT) Data Release 4 and 6 at frequencies of roughly 93, 148, and 225 GHz, together with data from the \textit{Planck} satellite at frequencies between 30 GHz and 545 GHz. We present detailed verification of an internal linear combination pipeline implemented in a needlet frame that allows us to efficiently suppress Galactic contamination and account for spatial variations in the ACT instrument noise. These maps provide a significant advance, in noise levels and resolution, over the existing \textit{Planck} component-separated maps and will enable a host of science goals including studies of cluster and galaxy astrophysics, inferences of the cosmic velocity field, primordial non-Gaussianity searches, and gravitational lensing reconstruction of the CMB.Comment: The Compton-y map and associated products will be made publicly available upon publication of the paper. The CMB T and E mode maps will be made available when the DR6 maps are made publi

    The Atacama Cosmology Telescope: DR6 Gravitational Lensing Map and Cosmological Parameters

    Full text link
    We present cosmological constraints from a gravitational lensing mass map covering 9400 sq. deg. reconstructed from CMB measurements made by the Atacama Cosmology Telescope (ACT) from 2017 to 2021. In combination with BAO measurements (from SDSS and 6dF), we obtain the amplitude of matter fluctuations σ8=0.819±0.015\sigma_8 = 0.819 \pm 0.015 at 1.8% precision, S8σ8(Ωm/0.3)0.5=0.840±0.028S_8\equiv\sigma_8({\Omega_{\rm m}}/0.3)^{0.5}=0.840\pm0.028 and the Hubble constant H0=(68.3±1.1)kms1Mpc1H_0= (68.3 \pm 1.1)\, \text{km}\,\text{s}^{-1}\,\text{Mpc}^{-1} at 1.6% precision. A joint constraint with CMB lensing measured by the Planck satellite yields even more precise values: σ8=0.812±0.013\sigma_8 = 0.812 \pm 0.013, S8σ8(Ωm/0.3)0.5=0.831±0.023S_8\equiv\sigma_8({\Omega_{\rm m}}/0.3)^{0.5}=0.831\pm0.023 and H0=(68.1±1.0)kms1Mpc1H_0= (68.1 \pm 1.0)\, \text{km}\,\text{s}^{-1}\,\text{Mpc}^{-1}. These measurements agree well with Λ\LambdaCDM-model extrapolations from the CMB anisotropies measured by Planck. To compare these constraints to those from the KiDS, DES, and HSC galaxy surveys, we revisit those data sets with a uniform set of assumptions, and find S8S_8 from all three surveys are lower than that from ACT+Planck lensing by varying levels ranging from 1.7-2.1σ\sigma. These results motivate further measurements and comparison, not just between the CMB anisotropies and galaxy lensing, but also between CMB lensing probing z0.55z\sim 0.5-5 on mostly-linear scales and galaxy lensing at z0.5z\sim 0.5 on smaller scales. We combine our CMB lensing measurements with CMB anisotropies to constrain extensions of Λ\LambdaCDM, limiting the sum of the neutrino masses to mν<0.12\sum m_{\nu} < 0.12 eV (95% c.l.), for example. Our results provide independent confirmation that the universe is spatially flat, conforms with general relativity, and is described remarkably well by the Λ\LambdaCDM model, while paving a promising path for neutrino physics with gravitational lensing from upcoming ground-based CMB surveys.Comment: 30 pages, 16 figures, prepared for submission to ApJ. Cosmological likelihood data is here: https://lambda.gsfc.nasa.gov/product/act/actadv_prod_table.html ; likelihood software is here: https://github.com/ACTCollaboration/act_dr6_lenslike . Also see companion papers Qu et al and MacCrann et al. Mass maps will be released when papers are publishe

    Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

    Get PDF

    CMB-S4: Forecasting Constraints on Primordial Gravitational Waves

    Full text link
    CMB-S4---the next-generation ground-based cosmic microwave background (CMB) experiment---is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the Universe, from the highest energies at the dawn of time through the growth of structure to the present day. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semi-analytic projection tool, targeted explicitly towards optimizing constraints on the tensor-to-scalar ratio, rr, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2--3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments given a desired scientific goal. To form a closed-loop process, we couple this semi-analytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for r>0.003r > 0.003 at greater than 5σ5\sigma, or, in the absence of a detection, of reaching an upper limit of r<0.001r < 0.001 at 95%95\% CL.Comment: 24 pages, 8 figures, 9 tables, submitted to ApJ. arXiv admin note: text overlap with arXiv:1907.0447

    Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

    Get PDF
    Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

    The Atacama Cosmology Telescope: A measurement of the DR6 CMB lensing power spectrum and its implications for structure growth

    Get PDF
    We present new measurements of cosmic microwave background (CMB) lensing over 9400 deg2 of the sky. These lensing measurements are derived from the Atacama Cosmology Telescope (ACT) Data Release 6 (DR6) CMB data set, which consists of five seasons of ACT CMB temperature and polarization observations. We determine the amplitude of the CMB lensing power spectrum at 2.3% precision (43σ significance) using a novel pipeline that minimizes sensitivity to foregrounds and to noise properties. To ensure that our results are robust, we analyze an extensive set of null tests, consistency tests, and systematic error estimates and employ a blinded analysis framework. Our CMB lensing power spectrum measurement provides constraints on the amplitude of cosmic structure that do not depend on Planck or galaxy survey data, thus giving independent information about large-scale structure growth and potential tensions in structure measurements. The baseline spectrum is well fit by a lensing amplitude of A lens = 1.013 ± 0.023 relative to the Planck 2018 CMB power spectra best-fit ΛCDM model and A lens = 1.005 ± 0.023 relative to the ACT DR4 + WMAP best-fit model. From our lensing power spectrum measurement, we derive constraints on the parameter combination S8CMBL≡σ8Ωm/0.30.25 of S8CMBL=0.818±0.022 from ACT DR6 CMB lensing alone and S8CMBL=0.813±0.018 when combining ACT DR6 and Planck NPIPE CMB lensing power spectra. These results are in excellent agreement with ΛCDM model constraints from Planck or ACT DR4 + WMAP CMB power spectrum measurements. Our lensing measurements from redshifts z ∼ 0.5–5 are thus fully consistent with ΛCDM structure growth predictions based on CMB anisotropies probing primarily z ∼ 1100. We find no evidence for a suppression of the amplitude of cosmic structure at low redshifts
    corecore