Tiered Human Integrated Sequence Search Databases for Shotgun Proteomics.

The results of analysis of shotgun proteomics mass spectrometry data can be greatly affected by the selection of the reference protein sequence database against which the spectra are matched. For many species there are multiple sources from which somewhat different sequence sets can be obtained. This can lead to confusion about which database is best in which circumstances-a problem especially acute in human sample analysis. All sequence databases are genome-based, with sequences for the predicted gene and their protein translation products compiled. Our goal is to create a set of primary sequence databases that comprise the union of sequences from many of the different available sources and make the result easily available to the community. We have compiled a set of four sequence databases of varying sizes, from a small database consisting of only the ∼20,000 primary isoforms plus contaminants to a very large database that includes almost all nonredundant protein sequences from several sources. This set of tiered, increasingly complete human protein sequence databases suitable for mass spectrometry proteomics sequence database searching is called the Tiered Human Integrated Search Proteome set. In order to evaluate the utility of these databases, we have analyzed two different data sets, one from the HeLa cell line and the other from normal human liver tissue, with each of the four tiers of database complexity. The result is that approximately 0.8%, 1.1%, and 1.5% additional peptides can be identified for Tiers 2, 3, and 4, respectively, as compared with the Tier 1 database, at substantially increasing computational cost. This increase in computational cost may be worth bearing if the identification of sequence variants or the discovery of sequences that are not present in the reviewed knowledge base entries is an important goal of the study. We find that it is useful to search a data set against a simpler database, and then check the uniqueness of the discovered peptides against a more complex database. We have set up an automated system that downloads all the source databases on the first of each month and automatically generates a new set of search databases and makes them available for download at http://www.peptideatlas.org/thisp/

Development of data representation standards by the human proteome organization proteomics standards initiative.

OBJECTIVE: To describe the goals of the Proteomics Standards Initiative (PSI) of the Human Proteome Organization, the methods that the PSI has employed to create data standards, the resulting output of the PSI, lessons learned from the PSI's evolution, and future directions and synergies for the group. MATERIALS AND METHODS: The PSI has 5 categories of deliverables that have guided the group. These are minimum information guidelines, data formats, controlled vocabularies, resources and software tools, and dissemination activities. These deliverables are produced via the leadership and working group organization of the initiative, driven by frequent workshops and ongoing communication within the working groups. Official standards are subjected to a rigorous document process that includes several levels of peer review prior to release. RESULTS: We have produced and published minimum information guidelines describing what information should be provided when making data public, either via public repositories or other means. The PSI has produced a series of standard formats covering mass spectrometer input, mass spectrometer output, results of informatics analysis (both qualitative and quantitative analyses), reports of molecular interaction data, and gel electrophoresis analyses. We have produced controlled vocabularies that ensure that concepts are uniformly annotated in the formats and engaged in extensive software development and dissemination efforts so that the standards can efficiently be used by the community.Conclusion In its first dozen years of operation, the PSI has produced many standards that have accelerated the field of proteomics by facilitating data exchange and deposition to data repositories. We look to the future to continue developing standards for new proteomics technologies and workflows and mechanisms for integration with other omics data types. Our products facilitate the translation of genomics and proteomics findings to clinical and biological phenotypes. The PSI website can be accessed at http://www.psidev.info

Spatial and epidemiological drivers of Plasmodium falciparum malaria among adults in the Democratic Republic of the Congo

Background Adults are frequently infected with malaria and may serve as a reservoir for further transmission, yet we know relatively little about risk factors for adult infections. In this study, we assessed malaria risk factors among adults using samples from the nationally representative, cross-sectional 2013-2014 Demographic and Health Survey (DHS) conducted in the Democratic Republic of the Congo (DRC). We further explored differences in risk factors by urbanicity. Methods Plasmodium falciparum infection was determined by PCR. Covariates were drawn from the DHS to model individual, community and environmental-level risk factors for infection. Additionally, we used deep sequencing data to estimate the community-level proportions of drug-resistant infections and included these estimates as potential risk factors. All identified factors were assessed for differences in associations by urbanicity. Results A total of 16 126 adults were included. Overall prevalence of malaria was 30.3% (SE=1.1) by PCR; province-level prevalence ranged from 6.7% to 58.3%. Only 17% of individuals lived in households with at least one bed-net for every two people, as recommended by the WHO. Protective factors included increasing within-household bed-net coverage (Prevalence Ratio=0.85, 95% CI=0.76-0.95) and modern housing (PR=0.58, 95% CI=0.49-0.69). Community-level protective factors included increased median wealth (PR=0.87, 95% CI=0.83-0.92). Education, wealth, and modern housing showed protective associations in cities but not in rural areas. Conclusions The DRC continues to suffer from a high burden of malaria; interventions that target high-risk groups and sustained investment in malaria control are sorely needed. Areas of high prevalence should be prioritised for interventions to target the largest reservoirs for further transmission

Combination of searches for Higgs boson pairs in pp collisions at \sqrts = 13 TeV with the ATLAS detector

This letter presents a combination of searches for Higgs boson pair production using up to 36.1 fb(-1) of proton-proton collision data at a centre-of-mass energy root s = 13 TeV recorded with the ATLAS detector at the LHC. The combination is performed using six analyses searching for Higgs boson pairs decaying into the b (b) over barb (b) over bar, b (b) over barW(+)W(-), b (b) over bar tau(+)tau(-), W+W-W+W-, b (b) over bar gamma gamma and W+W-gamma gamma final states. Results are presented for non-resonant and resonant Higgs boson pair production modes. No statistically significant excess in data above the Standard Model predictions is found. The combined observed (expected) limit at 95% confidence level on the non-resonant Higgs boson pair production cross-section is 6.9 (10) times the predicted Standard Model cross-section. Limits are also set on the ratio (kappa(lambda)) of the Higgs boson self-coupling to its Standard Model value. This ratio is constrained at 95% confidence level in observation (expectation) to -5.0 &lt; kappa(lambda) &lt; 12.0 (-5.8 &lt; kappa(lambda) &lt; 12.0). In addition, limits are set on the production of narrow scalar resonances and spin-2 Kaluza-Klein Randall-Sundrum gravitons. Exclusion regions are also provided in the parameter space of the habemus Minimal Supersymmetric Standard Model and the Electroweak Singlet Model. For complete list of authors see http://dx.doi.org/10.1016/j.physletb.2019.135103</p

Searches for lepton-flavour-violating decays of the Higgs boson in s=13\sqrt{s}=13 TeV pp\mathit{pp} collisions with the ATLAS detector

This Letter presents direct searches for lepton flavour violation in Higgs boson decays, H → eτ and H → μτ , performed with the ATLAS detector at the LHC. The searches are based on a data sample of proton–proton collisions at a centre-of-mass energy √s = 13 TeV, corresponding to an integrated luminosity of 36.1 fb−1. No significant excess is observed above the expected background from Standard Model processes. The observed (median expected) 95% confidence-level upper limits on the leptonflavour-violating branching ratios are 0.47% (0.34+0.13−0.10%) and 0.28% (0.37+0.14−0.10%) for H → eτ and H → μτ , respectively.publishedVersio

Search for flavour-changing neutral currents in processes with one top quark and a photon using 81 fb⁻¹ of pp collisions at \sqrts = 13 TeV with the ATLAS experiment

A search for flavour-changing neutral current (FCNC) events via the coupling of a top quark, a photon, and an up or charm quark is presented using 81 fb−1 of proton–proton collision data taken at a centre-of-mass energy of 13 TeV with the ATLAS detector at the LHC. Events with a photon, an electron or muon, a b-tagged jet, and missing transverse momentum are selected. A neural network based on kinematic variables differentiates between events from signal and background processes. The data are consistent with the background-only hypothesis, and limits are set on the strength of the tqγ coupling in an effective field theory. These are also interpreted as 95% CL upper limits on the cross section for FCNC tγ production via a left-handed (right-handed) tuγ coupling of 36 fb (78 fb) and on the branching ratio for t→γu of 2.8×10−5 (6.1×10−5). In addition, they are interpreted as 95% CL upper limits on the cross section for FCNC tγ production via a left-handed (right-handed) tcγ coupling of 40 fb (33 fb) and on the branching ratio for t→γc of 22×10−5 (18×10−5). © 2019 The Author(s

Search for single vector-like B quark production and decay via B → bH(b¯b) in pp collisions at √s = 13 TeV with the ATLAS detector

A search is presented for single production of a vector-like B quark decaying into a Standard Model b-quark and a Standard Model Higgs boson, which decays into a b¯b pair. The search is carried out in 139 fb−1 of √s = 13 TeV proton-proton collision data collected by the ATLAS detector at the LHC between 2015 and 2018. No significant deviation from the Standard Model background prediction is observed, and mass-dependent exclusion limits at the 95% confidence level are set on the resonance production cross-section in several theoretical scenarios determined by the couplings cW, cZ and cH between the B quark and the Standard Model W, Z and Higgs bosons, respectively. For a vector-like B occurring as an isospin singlet, the search excludes values of cW greater than 0.45 for a B resonance mass (mB) between 1.0 and 1.2 TeV. For 1.2 TeV < mB < 2.0 TeV, cW values larger than 0.50–0.65 are excluded. If the B occurs as part of a (B, Y) doublet, the smallest excluded cZ coupling values range between 0.3 and 0.5 across the investigated resonance mass range 1.0 TeV < mB < 2.0 TeV