472 research outputs found
Unsupervised protein embeddings outperform hand-crafted sequence and structure features at predicting molecular function
Motivation: Protein function prediction is a difficult bioinformatics problem. Many recent methods use deep neural networks to learn complex sequence representations and predict function from these. Deep supervised models require a lot of labeled training data which are not available for this task. However, a very large amount of protein sequences without functional labels is available.Results: We applied an existing deep sequence model that had been pretrained in an unsupervised setting on the supervised task of protein molecular function prediction. We found that this complex feature representation is effective for this task, outperforming hand-crafted features such as one-hot encoding of amino acids, k-mer counts, secondary structure and backbone angles. Also, it partly negates the need for complex prediction models, as a two-layer perceptron was enough to achieve competitive performance in the third Critical Assessment of Functional Annotation benchmark. We also show that combining this sequence representation with protein 3D structure information does not lead to performance improvement, hinting that 3D structure is also potentially learned during the unsupervised pretraining
The genome sequencing of an albino Western lowland gorilla reveals inbreeding in the wild
Background The only known albino gorilla, named Snowflake, was a male wild born individual from Equatorial Guinea who lived at the Barcelona Zoo for almost 40 years. He was diagnosed with non-syndromic oculocutaneous albinism, i.e. white hair, light eyes, pink skin, photophobia and reduced visual acuity. Despite previous efforts to explain the genetic cause, this is still unknown. Here, we study the genetic cause of his albinism and making use of whole genome sequencing data we find a higher inbreeding coefficient compared to other gorillas. Results We successfully identified the causal genetic variant for Snowflake¿s albinism, a non-synonymous single nucleotide variant located in a transmembrane region of SLC45A2. This transporter is known to be involved in oculocutaneous albinism type 4 (OCA4) in humans. We provide experimental evidence that shows that this amino acid replacement alters the membrane spanning capability of this transmembrane region. Finally, we provide a comprehensive study of genome-wide patterns of autozygogosity revealing that Snowflake¿s parents were related, being this the first report of inbreeding in a wild born Western lowland gorilla. Conclusions In this study we demonstrate how the use of whole genome sequencing can be extended to link genotype and phenotype in non-model organisms and it can be a powerful tool in conservation genetics (e.g., inbreeding and genetic diversity) with the expected decrease in sequencing cost. Keywords: Gorilla; Albinism; Inbreeding; Genome; Conservatio
Genome-Wide Association Study of the Modified Stumvoll Insulin Sensitivity Index Identifies BCL2 and FAM19A2 as Novel Insulin Sensitivity Loci
Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed a GWAS of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-Related Traits Consortium. Discovery for genetic association was performed in 16,753 individuals, and replication was attempted for the 23 most significant novel loci in 13,354 independent individuals. Association with ISI was tested in models adjusted for age, sex, and BMI and in a model analyzing the combined influence of the genotype effect adjusted for BMI and the interaction effect between the genotype and BMI on ISI (model 3). In model 3, three variants reached genome-wide significance: Rs13422522 (NYAP2; P = 8.87 × 10-11), rs12454712 (BCL2; P = 2.7 × 10-8), and rs10506418 (FAM19A2; P = 1.9 × 10-8). The association at NYAP2 was eliminated by conditioning on the known IRS1 insulin sensitivity locus; the BCL2 and FAM19A2 associations were independent of known cardiometabolic loci. In conclusion, we identified two novel loci and replicated known variants associated with insulin sensitivity. Further studies are needed to clarify the causal variant and function at the BCL2 and FAM19A2 loci
Nucleic acid amplification tests in the diagnosis of tuberculous pleuritis: a systematic review and meta-analysis
BACKGROUND: Conventional tests for tuberculous pleuritis have several limitations. A variety of new, rapid tests such as nucleic acid amplification tests – including polymerase chain reaction – have been evaluated in recent times. We conducted a systematic review to determine the accuracy of nucleic acid amplification (NAA) tests in the diagnosis of tuberculous pleuritis. METHODS: A systematic review and meta-analysis of 38 English and Spanish articles (with 40 studies), identified via searches of six electronic databases, hand searching of selected journals, and contact with authors, experts, and test manufacturers. Sensitivity, specificity, and other measures of accuracy were pooled using random effects models. Summary receiver operating characteristic curves were used to summarize overall test performance. Heterogeneity in study results was formally explored using subgroup analyses. RESULTS: Of the 40 studies included, 26 used in-house ("home-brew") tests, and 14 used commercial tests. Commercial tests had a low overall sensitivity (0.62; 95% confidence interval [CI] 0.43, 0.77), and high specificity (0.98; 95% CI 0.96, 0.98). The positive and negative likelihood ratios for commercial tests were 25.4 (95% CI 16.2, 40.0) and 0.40 (95% CI 0.24, 0.67), respectively. All commercial tests had consistently high specificity estimates; the sensitivity estimates, however, were heterogeneous across studies. With the in-house tests, both sensitivity and specificity estimates were significantly heterogeneous. Clinically meaningful summary estimates could not be determined for in-house tests. CONCLUSIONS: Our results suggest that commercial NAA tests may have a potential role in confirming (ruling in) tuberculous pleuritis. However, these tests have low and variable sensitivity and, therefore, may not be useful in excluding (ruling out) the disease. NAA test results, therefore, cannot replace conventional tests; they need to be interpreted in parallel with clinical findings and results of conventional tests. The accuracy of in-house nucleic acid amplification tests is poorly defined because of heterogeneity in study results. The clinical applicability of in-house NAA tests remains unclear
Studies of and production in and Pb collisions
The production of and mesons is studied in proton-proton and
proton-lead collisions collected with the LHCb detector. Proton-proton
collisions are studied at center-of-mass energies of and ,
and proton-lead collisions are studied at a center-of-mass energy per nucleon
of . The studies are performed in center-of-mass rapidity
regions (forward rapidity) and
(backward rapidity) defined relative to the proton beam direction. The
and production cross sections are measured differentially as a function
of transverse momentum for and , respectively. The differential cross sections are used to
calculate nuclear modification factors. The nuclear modification factors for
and mesons agree at both forward and backward rapidity, showing
no significant evidence of mass dependence. The differential cross sections of
mesons are also used to calculate cross section ratios,
which show evidence of a deviation from the world average. These studies offer
new constraints on mass-dependent nuclear effects in heavy-ion collisions, as
well as and meson fragmentation.Comment: All figures and tables, along with machine-readable versions and any
supplementary material and additional information, are available at
https://lhcbproject.web.cern.ch/Publications/p/LHCb-PAPER-2023-030.html (LHCb
public pages
Fraction of decays in prompt production measured in pPb collisions at TeV
The fraction of and decays in the prompt
yield, , is measured by
the LHCb detector in pPb collisions at TeV. The study
covers the forward () and backward () rapidity
regions, where is the rapidity in the nucleon-nucleon
center-of-mass system. Forward and backward rapidity samples correspond to
integrated luminosities of 13.6 0.3 nb and 20.8 0.5
nb, respectively. The result is presented as a function of the
transverse momentum in the range 1 GeV/.
The fraction at forward rapidity is compatible with the LHCb
measurement performed in collisions at TeV, whereas the
result at backward rapidity is 2.4 larger than in the forward region
for GeV/. The increase of at low at backward rapidity is compatible with the suppression of the
(2S) contribution to the prompt yield. The lack of in-medium
dissociation of states observed in this study sets an upper limit of
180 MeV on the free energy available in these pPb collisions to dissociate or
inhibit charmonium state formation.Comment: All figures and tables, along with machine-readable versions and any
supplementary material and additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-028.html (LHCb
public pages
Enhanced production of baryons in high-multiplicity collisions at TeV
The production rate of baryons relative to mesons
in collisions at a center-of-mass energy TeV is measured
by the LHCb experiment. The ratio of to production
cross-sections shows a significant dependence on both the transverse momentum
and the measured charged-particle multiplicity. At low multiplicity, the ratio
measured at LHCb is consistent with the value measured in
collisions, and increases by a factor of with increasing multiplicity.
At relatively low transverse momentum, the ratio of to
cross-sections is higher than what is measured in
collisions, but converges with the ratio as the momentum
increases. These results imply that the evolution of heavy quarks into
final-state hadrons is influenced by the density of the hadronic environment
produced in the collision. Comparisons with a statistical hadronization model
and implications for the mechanisms enforcing quark confinement are discussed.Comment: All figures and tables, along with machine-readable versions and any
supplementary material and additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-027.html (LHCb
public pages
A measurement of
Using a dataset corresponding to of integrated
luminosity collected with the LHCb detector between 2011 and 2018 in
proton-proton collisions, the decay-time distributions of the decay modes
and
are studied. The decay-width difference between the light and heavy mass
eigenstates of the meson is measured to be , where the first uncertainty is
statistical and the second systematic.Comment: All figures and tables, along with machine-readable versions and any
supplementary material and additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-025.htm
Helium identification with LHCb
The identification of helium nuclei at LHCb is achieved using a method based
on measurements of ionisation losses in the silicon sensors and timing
measurements in the Outer Tracker drift tubes. The background from photon
conversions is reduced using the RICH detectors and an isolation requirement.
The method is developed using collision data at
recorded by the LHCb experiment in the years 2016 to 2018, corresponding to an
integrated luminosity of . A total of around helium
and antihelium candidates are identified with negligible background
contamination. The helium identification efficiency is estimated to be
approximately with a corresponding background rejection rate of up to
. These results demonstrate the feasibility of a rich
programme of measurements of QCD and astrophysics interest involving light
nuclei.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-DP-2023-002.html (LHCb public
pages
Observation of the decays
This paper reports the observation of the decays using proton-proton collision data collected by the
LHCb experiment, corresponding to an integrated luminosity of
. The branching fractions of these decays are measured
relative to the normalisation channel .
The meson is reconstructed in the
decay channel and the products of branching
fractions are measured to be The first uncertainty is
statistical, the second systematic, and the third arises from the uncertainty
of the branching fraction of the
normalisation channel. The last uncertainty in the result is due to
the limited knowledge of the fragmentation fraction ratio, . The
significance for the and signals is larger than
. The ratio of the helicity amplitudes which governs the angular
distribution of the decay
is determined from the data. The ratio of the - and -wave amplitudes is
found to be and its phase rad,
where the first uncertainty is statistical and the second systematic.Comment: All figures and tables, along with machine-readable versions and any
supplementary material and additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-014.html (LHCb
public pages
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