414 Works

Estimating the Net Value of Treating Hepatitis C Virus Using Newly Available Direct-Acting Antivirals in India (Supporting Datasets)

David Bloom, Alex Khoury & V. Srinivasan
Recently developed direct-acting antiviral (DAA) treatments for hepatitis C virus (HCV) have been groundbreaking for their high efficacy across disease genotypes and lack of severe side effects. This study uses a cost-of-illness (COI) approach to estimate the net value conferred by this class of drugs using the cost and efficacy of one of these novel drug combinations, sofosbuvir and velpatasvir (SOF/VEL), recently licensed for generic manufacture in India. This study considers COI of lifetime earnings...

Data from: Non-invasive stratification of non-alcoholic fatty liver disease by whole-transcriptome cell-free mRNA characterization

Naga Chalsani, Shusuke Toden, John Sninsky, Richard Rava, Jerome Braun, Samer Gawrieh, Jiali Zhuang, Michael Nerenberg, Stephen Quake & Tara Maddala
Hepatic fibrosis stage is the most important determinant of outcomes in patients with non-alcoholic fatty liver disease (NAFLD). There is an urgent need for non-invasive tests that can accurately stage fibrosis and determine efficacy of interventions. Here we describe a novel cf-mRNA-Sequencing approach that can accurately and reproducibly profile low levels of circulating mRNAs and evaluate the feasibility of developing a cf-mRNA-based NAFLD fibrosis classifier. Using separate discovery and validation cohorts with biopsy-confirmed NAFLD (n=176...

Data from: Covariation of diet and gut microbiome in African megafauna

Tyler R. Kartzinel, Julianna C. Hsing, Paul M. Musili, Bianca R. P. Brown & Robert M. Pringle
A major challenge in biology is to understand how phylogeny, diet, and environment shape the mammalian gut microbiome. Yet most studies of non-human microbiomes have relied on relatively coarse dietary categorizations and have focused either on individual wild populations or on captive animals that are sheltered from environmental pressures, which may obscure the effects of dietary and environmental variation on microbiome composition in diverse natural communities. We analyzed plant and bacterial DNA in fecal samples...

Data for: Landscape scale variation in the hydrologic niche of California coast redwood

Emily J. Francis, Gregory P. Asner, Katharine J. Mach & Christopher B. Field
Topoclimatic diversity within forest landscapes can underlie variation in water availability, which may correspond to patterns in habitat suitability of tree species with differing hydrologic niches. However, the trade-off between the collection of data at a fine grain size over large spatial extents has limited comprehensive analyses of landscape scale variation in habitat suitability. We present a fine scale analysis of the roles of topographic gradients in moisture availability, soil water storage, and fog frequency...

Distinct DNA methylation signatures in neuroendocrine tumors specific for primary site and inherited predisposition

Amit Tirosh, Jonathan Keith Killian, David Petersen, Yuelin Jack Zhu, Robert L Walker, Jenny E Blau, Naris Nilubol, Dhaval Patel, Sunita K Agarwal, Lee Scott Weinstein, Paul Meltzer & Electron Kebebew
Purpose: To compare the deoxyribonucleic acid (DNA) methylation signature of neuroendocrine tumors (NETs) by primary tumor site and inherited predisposition syndromes von Hippel–Lindau disease (VHL) and multiple endocrine neoplasia type 1 (MEN1). Methods Genome-wide DNA methylation (835 424 CpGs) of 96 NET samples. Principal components analysis (PCA) and unsupervised hierarchical clustering analyses were used to determine DNA methylome signatures. Results: Hypomethylated CpGs were significantly more common in VHL-related versus sporadic and MEN1-related NETs (P <...

Data from: Fate of internal waves on a shallow shelf

Kristen Davis, Robert Arthur, Emma Reid, Thomas DeCarlo, Anne Cohen, Oliver Fringer & Justin Rogers
Internal waves strongly influence the physical and chemical environment of coastal ecosystems worldwide. We report novel observations from a distributed temperature sensing (DTS) system that tracked the transformation of internal waves from the shelf break to the surf zone over a narrow shelf-slope region in the South China Sea. The spatially-continuous view of temperature fields provides a perspective of physical processes commonly available only in laboratory settings or numerical models, including internal wave reflection off...

Footprints of local adaptation span hundreds of linked genes in the Atlantic silverside genome

Aryn Wilder, Stephen Palumbi, David Conover & Nina Overgaard Therkildsen
The study of local adaptation in the presence of ongoing gene flow is the study of natural selection in action, revealing the functional genetic diversity most relevant to contemporary pressures. In addition to individual genes, genome-wide architecture can itself evolve to enable adaptation. Distributed across a steep thermal gradient along the east coast of North America, Atlantic silversides (Menidia menidia) exhibit an extraordinary degree of local adaptation in a suite of traits, and the capacity...

The evolutionary dynamics and fitness landscape of clonal hematopoiesis

Caroline J. Watson, A.L. Papula, Gladys Y.P. Poon, Wing H. Wong, Andrew L. Young, Todd E. Druley, Daniel S. Fisher & Jamie R. Blundell
Somatic mutations acquired in healthy tissues as we age are major determinants of cancer risk. Whether variants confer a fitness advantage or rise to detectable frequencies by change remains largely unknown. Blood sequencing data from ∼50,000 individuals reveals how mutation, genetic drift and fitness shape the genetic diversity of healthy blood (clonal hematopoiesis). We show that positive selection, not drift, is the major force shaping clonal hematopoiesis, provide bounds on the number of hematopoietic stem...

Comprehensive investigation of circulating biomarkers and their causal role in atherosclerosis-related risk factors and clinical events

Daniela Zanetti
Background: Circulating biomarkers have been previously associated with atherosclerosis-related risk factors, but the nature of these associations is incompletely understood. Methods: We performed multivariable-adjusted regressions and 2-sample Mendelian randomization analyses to assess observational and causal associations of 27 circulating biomarkers with 7 cardiovascular traits in up to 451 933 participants of the UK Biobank. Results: After multiple-testing correction (alpha=1.3Å~10−4), we found a total of 15, 9, 21, 22, 26, 24, and 26 biomarkers strongly associated...

Data from: Facilitation and biodiversity jointly drive mutualistic networks

Gianalberto Losapio, Elizabeth Norton Hasday, Xavier Espadaler, Christoph Germann, Francisco Javier Ortiz-Sánchez, Adrian Pont, Daniele Sommaggio & Christian Schöb
1. Facilitation by nurse plants increases understorey diversity and supports ecological communities. In turn, biodiversity shapes ecological networks and enhances ecosystem functioning. However, whether and how facilitation and increased biodiversity jointly influence community structure and ecosystem functioning remains unclear. 2. We performed a field experiment disentangling the relative contribution of nurse plants and increasing understorey plant diversity in driving pollination interactions. Both the presence of nurse shrubs as well as increased understorey plant diversity increased...

Data for: Modeling short-term energetic costs of sonar disturbance to cetaceans using high resolution foraging data

Max Czapanskiy, Matthew Savoca, William Gough, Paolo Segre, Danuta Wisniewska, David Cade & Jeremy Goldbogen
Anthropogenic noise is a pervasive and increasing source of disturbance to wildlife. Marine mammals exhibit behavioral and physiological responses to naval sonar and other sound sources. The lost foraging opportunities and elevated locomotor effort associated with sonar disturbance likely carry energetic costs, which may lead to population-level consequences. We modeled the energetic costs associated with behavioral responses using (1) empirical datasets of cetacean feeding rates and prey characteristics and (2) allometry of swimming performance and...

Microcoleus (Cyanobacteria) form watershed-wide populations without strong gradients in population structure

Keith Bouma-Gregson, Alex Crits-Christoph, Matthew Olm, Mary Power & Jillian Banfield
The relative importance of separation by distance and by environment to population genetic diversity can be conveniently tested in river networks, where these two drivers are often independently distributed over space. To evaluate the importance of dispersal and environmental conditions in shaping microbial population structures, we performed genome-resolved metagenomic analyses of benthic Microcoleus-dominated cyanobacterial mats collected in the Eel and Russian River networks (California, USA). The 64 Microcoleus genomes were clustered into three species that...

Data from: A new low-turbulence wind tunnel for animal and small vehicle flight experiments

Daniel B. Quinn, Anthony Watts, Tony Nagle & David Lentink
Our understanding of animal flight benefits greatly from specialized wind tunnels designed for flying animals. Existing facilities can simulate laminar flow during straight, ascending and descending flight, as well as at different altitudes. However, the atmosphere in which animals fly is even more complex. Flow can be laminar and quiet at high altitudes but highly turbulent near the ground, and gusts can rapidly change wind speed. To study flight in both laminar and turbulent environments,...

Data from: Strong coupling of plant and fungal community structure across western Amazonian rainforests

Kabir G. Peay, Christopher Baraloto & Paul V. A. Fine
The Amazon basin harbors a diverse ecological community that has a critical role in the maintenance of the biosphere. Although plant and animal communities have received much attention, basic information is lacking for fungal or prokaryotic communities. This is despite the fact that recent ecological studies have suggested a prominent role for interactions with soil fungi in structuring the diversity and abundance of tropical rainforest trees. In this study, we characterize soil fungal communities across...

Data from: Determining the genetic basis of anthracycline-cardiotoxicity by response QTL mapping in induced cardiomyocytes

David A. Knowles, Courtney K. Burrows, John D. Blischak, Kristen M. Patterson, Daniel J. Serie, Nadine Norton, Carole Ober, Jonathan K. Pritchard & Yoav Gilad
Anthracycline-induced cardiotoxicity (ACT) is a key limiting factor in setting optimal chemotherapy regimes, with almost half of patients expected to develop congestive heart failure given high doses. However, the genetic basis of sensitivity to anthracyclines remains unclear. We created a panel of iPSC-derived cardiomyocytes from 45 individuals and performed RNA-seq after 24h exposure to varying doxorubicin dosages. The transcriptomic response is substantial: the majority of genes are differentially expressed and over 6000 genes show evidence...

Data from: Fast and cost-effective genetic mapping in apple using next-generation sequencing

Kyle M. Gardner, Thomas F. Cooke, Patrick J. Brown, Scott Cann, Fabrizio Costa, Carlos D. Bustamante, Riccardo Velasco, Michela Troggio, Sean Myles, P. Brown & C. Bustamante
Next-generation DNA sequencing (NGS) produces vast amounts of DNA sequence data, but it is not specifically designed to generate data suitable for genetic mapping. Recently developed DNA library preparation methods for NGS have helped solve this problem, however, by combining the use of reduced representation libraries with DNA sample barcoding to generate genome-wide genotype data from a common set of genetic markers across a large number of samples. Here we use such a method, called...

Data from: Long-term live imaging of the Drosophila adult midgut reveals real-time dynamics of division, differentiation, and loss

Judy Lisette Martin, Erin Nicole Sanders, Paola Moreno-Roman, Leslie Ann Jaramillo Koyama, Shruthi Balachandra, XinXin Du & Lucy Erin O'Brien
Organ renewal is governed by the dynamics of cell division, differentiation, and loss. To study these dynamics in real time, we present a platform for extended live imaging of the adult Drosophila midgut, a premier genetic model for stem cell-based organs. A window cut into a living animal allows the midgut to be imaged while intact and physiologically functioning. This approach prolongs imaging sessions to 12-16 hours and yields movies that document cell and tissue...

Data from: Evolution of the exclusively human-pathogen Neisseria gonorrhoeae: human-specific engagement of immunoregulatory Siglecs

Corinna S. Landig, Ashley Hazel, Benjamin P. Kellman, Jerry J. Fong, Flavio Schwarz, Sarika Agarwal, Nissi Varki, Paola Massari, Nathan E. Lewis, Sanjay Ram & Ajit Varki
Neisseria gonorrhoeae causes the sexually transmitted disease gonorrhea exclusively in humans and uses multiple strategies to infect, including acquisition of host sialic acids that cap and mask lipooligosaccharide termini, while restricting complement activation. We hypothesized that gonococci selectively target human anti-inflammatory sialic acid-recognizing Siglec receptors on innate immune cells to blunt host responses, and that pro-inflammatory Siglecs and SIGLEC pseudogene polymorphisms represent host evolutionary adaptions to counteract this interaction. N. gonorrhoeae can indeed engage multiple...

Data from: From cacti to carnivores: improved phylotranscriptomic sampling and hierarchical homology inference provide further insight into the evolution of Caryophyllales

Joseph Frederic Walker, Ya Yang, Tao Feng, Alfonso Timoneda, Jessica Mikenas, Vera Hutchison, Caroline Edwards, Ning Wang, Sonia Ahluwalia, Julia Olivieri, Nathanael Walker-Hale, Lucas C. Majure, Raúl Puente, Gudrun Kadereit, Maximillian Lauterbach, Urs Eggli, Hilda Flores-Olvera, Helga Ochoterena, Samuel F. Brockington, Michael J. Moore & Stephen A. Smith
Premise of the Study— The Caryophyllales contains ~12,500 species and is known for its cosmopolitan distribution, convergence of trait evolution, and extreme adaptations. Some relationships within the Caryophyllales, like those of many large plant clades, remain unclear and phylogenetic studies often recover alternative hypotheses. We explore the utility of broad and dense transcriptome sampling across the order for resolving evolutionary relationships in Caryophyllales. Methods— We generated 84 transcriptomes and combined these with 224 publicly available...

Data from: Indexed PCR primers induce template-specific bias in large-scale DNA sequencing studies

James L. O'Donnell, Ryan P. Kelly, Jesse A. Port, Natalie C. Lowell & James L. O’Donnell
Massively parallel sequencing is rapidly emerging as an efficient way to quantify biodiversity at all levels, from genetic variation and expression to ecological community assemblage. However, the number of reads produced per sequencing run far exceeds the number required per sample for many applications, compelling researchers to sequence multiple samples per run in order to maximize efficiency. For studies that include a PCR step, this can be accomplished using primers that include an index sequence...

Data from: U-Index, a dataset and an impact metric for informatics tools and databases

Alison Callahan, Rainer Winnenburg & Nigam H. Shah
Measuring the usage of informatics resources such as software tools and databases is essential to quantifying their impact, value and return on investment. We have developed a publicly available dataset of informatics resource publications and their citation network, along with an associated metric (u-Index) to measure informatics resources’ impact over time. Our dataset differentiates the context in which citations occur to distinguish between ‘awareness’ and ‘usage’, and uses a citing universe of open access publications...

Data from: Genomic sequencing reveals historical, demographic and selective factors associated with the diversification of the fire-associated fungus Neurospora discreta

Pierre Gladieux, Benjamin A. Wilson, Fanny Perraudeau, Liliam A. Montoya, David Kowbel, Christopher Hann-Soden, Monika Fischer, Iman Sylvain, David J. Jacobson & John W. Taylor
Delineating microbial populations, discovering ecologically relevant phenotypes and identifying migrants, hybrids or admixed individuals have long proved notoriously difficult, thereby limiting our understanding of the evolutionary forces at play during the diversification of microbial species. However, recent advances in sequencing and computational methods have enabled an unbiased approach whereby incipient species and the genetic correlates of speciation can be identified by examining patterns of genomic variation within and between lineages. We present here a population...

Data from: Detection of human adaptation during the past 2000 years

Yair Field, Evan A. Boyle, Natalie Telis, Ziyue Gao, Kyle J. Gaulton, David Golan, Loic Yengo, Ghislain Rocheleau, Philippe Froguel, Mark I. McCarthy & Jonathan K. Pritchard
Detection of recent natural selection is a challenging problem in population genetics. Here we introduce the Singleton Density Score (SDS), a method to infer very recent changes in allele frequencies from contemporary genome sequences. Applied to data from the UK10K Project, SDS reflects allele frequency changes in the ancestors of modern Britons during the past ~2,000-3,000 years. We see strong signals of selection at lactase and the MHC, and in favor of blond hair and...

Data from: Genetic signature of adaptive peak shift in threespine stickleback

Sean M. Rogers, Patrick Tamkee, Brian Summers, Sarita Balabahadra, Melissa Marks, David E. Kingsley & Dolph Schluter
Transition of an evolving population to a new adaptive optimum is predicted to leave a signature in the distribution of effect sizes of fixed mutations. If they affect many traits (are pleiotropic), large effect mutations should contribute more when a population evolves to a farther adaptive peak than to a nearer peak. We tested this prediction in wild threespine stickleback fish (Gasterosteus aculeatus) by comparing the estimated frequency of large effect genetic changes underlying evolution...

Data from: Transforming water: social influence moderates psychological, physiological, and functional response to a placebo product

Alia J. Crum, Damon J. Phillips, J. Parker Goyer, Modupe Akinola & E. Tory Higgins
This paper investigates how social influence can alter physiological, psychological, and functional responses to a placebo product and how such responses influence the ultimate endorsement of the product. Participants consumed a product, "AquaCharge Energy Water," falsely-labeled as containing 200 mg of caffeine but which was actually plain spring water, in one of three conditions: a no social influence condition, a disconfirming social influence condition, and a confirming social influence condition. Results demonstrated that the effect...

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