102 research outputs found
F*** workflows: when parts of FAIR are missing
The FAIR principles for scientific data (Findable, Accessible, Interoperable,
Reusable) are also relevant to other digital objects such as research software
and scientific workflows that operate on scientific data. The FAIR principles
can be applied to the data being handled by a scientific workflow as well as
the processes, software, and other infrastructure which are necessary to
specify and execute a workflow. The FAIR principles were designed as
guidelines, rather than rules, that would allow for differences in standards
for different communities and for different degrees of compliance. There are
many practical considerations which impact the level of FAIR-ness that can
actually be achieved, including policies, traditions, and technologies. Because
of these considerations, obstacles are often encountered during the workflow
lifecycle that trace directly to shortcomings in the implementation of the FAIR
principles. Here, we detail some cases, without naming names, in which data and
workflows were Findable but otherwise lacking in areas commonly needed and
expected by modern FAIR methods, tools, and users. We describe how some of
these problems, all of which were overcome successfully, have motivated us to
push on systems and approaches for fully FAIR workflows.Comment: 6 pages, 0 figures, accepted to ERROR 2022 workshop (see
https://error-workshop.org/ for more information), to be published in
proceedings of IEEE eScience 202
In vitro production and immunogenicity of a Clostridium difficile spore-specific BclA3 glycopeptide conjugate vaccine
The BclA3 glycoprotein is a major component of the exosporangial layer of Clostridium difficile spores and in this study we demonstrate that this glycoprotein is a major spore surface associated antigen. Here, we confirm the role of SgtA glycosyltransferase (SgtA GT) in BclA3 glycosylation and recapitulate this process by expressing and purifying SgtA GT fused to MalE, the maltose binding protein from Escherichia coli. In vitro assays using the recombinant enzyme and BclA3 synthetic peptides demonstrated that SgtA GT was responsible for the addition of β-O-linked GlcNAc to threonine residues of each synthetic peptide. These peptide sequences were selected from the central, collagen repeat region of the BclA3 protein. Following optimization of SgtA GT activity, we generated sufficient glycopeptide (10 mg) to allow conjugation to KLH (keyhole limpet hemocyanin) protein. Glycosylated and unglycosylated versions of these conjugates were then used as antigens to immunize rabbits and mice. Immune responses to each of the conjugates were examined by Enzyme Linked Immunosorbent Assay ELISA. Additionally, the BclA3 conjugated peptide and glycopeptide were used as antigens in an ELISA assay with serum raised against formalin-killed spores. Only the glycopeptide was recognized by anti-spore polyclonal immune serum demonstrating that the glycan moiety is a predominant spore-associated surface antigen. To determine whether antibodies to these peptides could modify persistence of spores within the gut, animals immunized intranasally with either the KLH-glycopeptide or KLH-peptide conjugate in the presence of cholera toxin, were challenged with R20291 spores. Although specific antibodies were raised to both antigens, immunization did not provide any protection against acute or recurrent disease
Ozone variability in the midlatitude upper troposphere and lower stratosphere diagnosed from a monthly SAGE II climatology relative to the tropopause
Activity patterns of free-ranging koalas (Phascolarctos cinereus) revealed by accelerometry
An understanding of koala activity patterns is important for measuring the behavioral response of this species to environmental change, but to date has been limited by the logistical challenges of traditional field methodologies. We addressed this knowledge gap by using tri-axial accelerometer data loggers attached to VHF radio collars to examine activity patterns of adult male and female koalas in a high-density population at Cape Otway, Victoria, Australia. Data were obtained from 27 adult koalas over two 7-d periods during the breeding season: 12 in the early-breeding season in November 2010, and 15 in the late-breeding season in January 2011. Multiple 15 minute observation blocks on each animal were used for validation of activity patterns determined from the accelerometer data loggers. Accelerometry was effective in distinguishing between inactive (sleeping, resting) and active (grooming, feeding and moving) behaviors. Koalas were more active during the early-breeding season with a higher index of movement (overall dynamic body acceleration [ODBA]) for both males and females. Koalas showed a distinct temporal pattern of behavior, with most activity occurring from mid-afternoon to early morning. Accelerometry has potential for examining fine-scale behavior of a wide range of arboreal and terrestrial species
TriTrypDB: a functional genomic resource for the Trypanosomatidae
TriTrypDB (http://tritrypdb.org) is an integrated database providing access to genome-scale datasets for kinetoplastid parasites, and supporting a variety of complex queries driven by research and development needs. TriTrypDB is a collaborative project, utilizing the GUS/WDK computational infrastructure developed by the Eukaryotic Pathogen Bioinformatics Resource Center (EuPathDB.org) to integrate genome annotation and analyses from GeneDB and elsewhere with a wide variety of functional genomics datasets made available by members of the global research community, often pre-publication. Currently, TriTrypDB integrates datasets from Leishmania braziliensis, L. infantum, L. major, L. tarentolae, Trypanosoma brucei and T. cruzi. Users may examine individual genes or chromosomal spans in their genomic context, including syntenic alignments with other kinetoplastid organisms. Data within TriTrypDB can be interrogated utilizing a sophisticated search strategy system that enables a user to construct complex queries combining multiple data types. All search strategies are stored, allowing future access and integrated searches. ‘User Comments’ may be added to any gene page, enhancing available annotation; such comments become immediately searchable via the text search, and are forwarded to curators for incorporation into the reference annotation when appropriate
Transcriptional recapitulation and subversion of embryonic colon development by mouse colon tumor models and human colon cancer
Colon tumors from four independent mouse models and 100 human colorectal cancers all exhibited striking recapitulation of embryonic colon gene expression from embryonic days 13.5-18.5
A Giant Planet Candidate Transiting a White Dwarf
Astronomers have discovered thousands of planets outside the solar system,
most of which orbit stars that will eventually evolve into red giants and then
into white dwarfs. During the red giant phase, any close-orbiting planets will
be engulfed by the star, but more distant planets can survive this phase and
remain in orbit around the white dwarf. Some white dwarfs show evidence for
rocky material floating in their atmospheres, in warm debris disks, or orbiting
very closely, which has been interpreted as the debris of rocky planets that
were scattered inward and tidally disrupted. Recently, the discovery of a
gaseous debris disk with a composition similar to ice giant planets
demonstrated that massive planets might also find their way into tight orbits
around white dwarfs, but it is unclear whether the planets can survive the
journey. So far, the detection of intact planets in close orbits around white
dwarfs has remained elusive. Here, we report the discovery of a giant planet
candidate transiting the white dwarf WD 1856+534 (TIC 267574918) every 1.4
days. The planet candidate is roughly the same size as Jupiter and is no more
than 14 times as massive (with 95% confidence). Other cases of white dwarfs
with close brown dwarf or stellar companions are explained as the consequence
of common-envelope evolution, wherein the original orbit is enveloped during
the red-giant phase and shrinks due to friction. In this case, though, the low
mass and relatively long orbital period of the planet candidate make
common-envelope evolution less likely. Instead, the WD 1856+534 system seems to
demonstrate that giant planets can be scattered into tight orbits without being
tidally disrupted, and motivates searches for smaller transiting planets around
white dwarfs.Comment: 50 pages, 12 figures, 2 tables. Published in Nature on Sept. 17,
2020. The final authenticated version is available online at:
https://www.nature.com/articles/s41586-020-2713-
Genetic Determinants of Lipid Traits in Diverse Populations from the Population Architecture using Genomics and Epidemiology (PAGE) Study
For the past five years, genome-wide association studies (GWAS) have identified hundreds of common variants associated with human diseases and traits, including high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels. Approximately 95 loci associated with lipid levels have been identified primarily among populations of European ancestry. The Population Architecture using Genomics and Epidemiology (PAGE) study was established in 2008 to characterize GWAS–identified variants in diverse population-based studies. We genotyped 49 GWAS–identified SNPs associated with one or more lipid traits in at least two PAGE studies and across six racial/ethnic groups. We performed a meta-analysis testing for SNP associations with fasting HDL-C, LDL-C, and ln(TG) levels in self-identified European American (∼20,000), African American (∼9,000), American Indian (∼6,000), Mexican American/Hispanic (∼2,500), Japanese/East Asian (∼690), and Pacific Islander/Native Hawaiian (∼175) adults, regardless of lipid-lowering medication use. We replicated 55 of 60 (92%) SNP associations tested in European Americans at p<0.05. Despite sufficient power, we were unable to replicate ABCA1 rs4149268 and rs1883025, CETP rs1864163, and TTC39B rs471364 previously associated with HDL-C and MAFB rs6102059 previously associated with LDL-C. Based on significance (p<0.05) and consistent direction of effect, a majority of replicated genotype-phentoype associations for HDL-C, LDL-C, and ln(TG) in European Americans generalized to African Americans (48%, 61%, and 57%), American Indians (45%, 64%, and 77%), and Mexican Americans/Hispanics (57%, 56%, and 86%). Overall, 16 associations generalized across all three populations. For the associations that did not generalize, differences in effect sizes, allele frequencies, and linkage disequilibrium offer clues to the next generation of association studies for these traits
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