Co-regulation map of the human proteome enables identification of protein functions

This is the author accepted manuscript. The final version is available from Nature Research via the DOI in this recordData availability: All mass spectrometry raw files generated in-house have been deposited in the ProteomeXchange Consortium (http://proteomecentral.proteomexchange.org) via the PRIDE partner repository36 with the dataset identifier PXD008888. The co-regulation map is hosted on our website at www.proteomeHD.net, and pair-wise co-regulation scores are available through STRING (https://string-db.org). A network of the top 0.5% co-regulated protein pairs can be explored interactively on NDEx (https://doi.org/10.18119/N9N30Q).Code availability: Data analysis was performed in R 3.5.1. R scripts and input files required to reproduce the results of this manuscript are available in the following GitHub repository: https://github.com/Rappsilber-Laboratory/ProteomeHD. R scripts related specifically to the benchmarking of the treeClust algorithm using synthetic data are available in the following GitHub repository: https://github.com/Rappsilber-Laboratory/treeClust-benchmarking. The R package data.table was used for fast data processing. Figures were prepared using ggplot2, gridExtra, cowplot and viridis.Note that the title of the AAM is different from the published versionThe annotation of protein function is a longstanding challenge of cell biology that suffers from the sheer magnitude of the task. Here we present ProteomeHD, which documents the response of 10,323 human proteins to 294 biological perturbations, measured by isotope-labelling mass spectrometry. We reveal functional associations between human proteins using the treeClust machine learning algorithm, which we show to improve protein co-regulation analysis due to robust selectivity for close linear relationships. Our co-regulation map identifies a functional context for many uncharacterized proteins, including microproteins that are difficult to study with traditional methods. Co-regulation also captures relationships between proteins which do not physically interact or co-localize. For example, co-regulation of the peroxisomal membrane protein PEX11β with mitochondrial respiration factors led us to discover a novel organelle interface between peroxisomes and mitochondria in mammalian cells. The co-regulation map can be explored at www.proteomeHD.net .Biotechnology & Biological Sciences Research Council (BBSRC)European Commissio

Measurement of transverse energy at midrapidity in Pb-Pb collisions at root s(NN)=2.76 TeV

We report the transverse energy (ET) measured with ALICE at midrapidity in Pb-Pb collisions at root s(NN) = 2.76 TeV as a function of centrality. The transverse energy was measured using identified single-particle tracks. The measurement was cross checked using the electromagnetic calorimeters and the transverse momentum distributions of identified particles previously reported by ALICE. The results are compared to theoretical models as well as to results from other experiments. The mean ET per unit pseudorapidity (eta), , in 0%-5% central collisions is 1737 +/- 6(stat.) +/- 97(sys.) GeV. We find a similar centrality dependence of the shape of as a function of the number of participating nucleons to that seen at lower energies. The growth in at the LHC energies exceeds extrapolations of low-energy data. We observe a nearly linear scaling of with the number of quark participants. With the canonical assumption of a 1 fm/c formation time, we estimate that the energy density in 0%-5% central Pb-Pb collisions at root s(NN) = 2.76 TeV is 12.3 +/- 1.0 GeV/fm(3) and that the energy density at the most central 80 fm(2) of the collision is at least 21.5 +/- 1.7 GeV/fm(3). This is roughly 2.3 times that observed in 0%-5% central Au-Au collisions at root s(NN) = 200 GeV.Peer reviewe

Azimuthally Differential Pion Femtoscopy in Pb-Pb Collisions at root s(NN)=2.76 TeV

We present the first azimuthally differential measurements of the pion source size relative to the second harmonic event plane in Pb-Pb collisions at a center-of-mass energy per nucleon-nucleon pair of root(NN)-N-s = 2.76 TeV. The measurements have been performed in the centrality range 0%-50% and for pion pair transverse momenta 0.2 <k(T) <0.7 GeV/c. We find that the R-side and R-out radii, which characterize the pion source size in the directions perpendicular and parallel to the pion transverse momentum, oscillate out of phase, similar to what was observed at the Relativistic Heavy Ion Collider. The final-state source eccentricity, estimated via R-side oscillations, is found to be significantly smaller than the initial-state source eccentricity, but remains positive-indicating that even after a stronger expansion in the in-plane direction, the pion source at the freeze-out is still elongated in the out-of-plane direction. The 3 + 1D hydrodynamic calculations are in qualitative agreement with observed centrality and transverse momentum R-side oscillations, but systematically underestimate the oscillation magnitude.Peer reviewe

D-meson production in p-Pb collisions at root S-NN=5.02 TeV and in pp collisions at root S=7 TeV

Peer reviewe

Correlated Event-by-Event Fluctuations of Flow Harmonics in Pb-Pb Collisions at root S-NN=2.76 TeV

Peer reviewe

J/Psi suppression at forward rapidity in Pb-Pb collisions at root s(NN)=5.02 TeV

The inclusive J/Psi production has been studied in Pb-Pb and pp collisions at the centre-of-mass energy per nucleon pair root sNN= 5.02TeV, using the ALICE detector at the CERN LHC. The J/Psi meson is reconstructed, in the centre-of-mass rapidity interval 2.5 <y <4and in the transverse- momentum range p(T)<12GeV/c, via its decay to a muon pair. In this Letter, we present results on the inclusive J/Psi cross section in pp collisions at root s= 5.02TeV and on the nuclear modification factor R-AA. The latter is presented as a function of the centrality of the collision and, for central collisions, as a function of the transverse momentum p(T) of the J/Psi. The measured R-AA values indicate a suppression of the J/Psi in nuclear collisions and are then compared to our previous results obtained in Pb-Pb collisions at root sNN= 2.76TeV. The ratio of the R-AA values at the two energies is also computed and compared to calculations of statistical and dynamical models. The numerical value of the ratio for central events (0-10% centrality) is 1.17 +/- 0.04( stat)+/- 0.20(syst). In central events, as a function of p(T), a slight increase of R-AA with collision energy is visible in the region 2 <p(T)<6GeV/c. Theoretical calculations qualitatively describe the measurements, within uncertainties. (C) 2017 The Author. Published by Elsevier B.V.Peer reviewe

Deconvolution assessment of splenic and splanchnic contributions to portal venous blood flow in liver cirrhosis

10.1118/1.3582691Medical Physics3852768-2782MPHY