Quantitative Mass Spectrometry Analysis Using PAcIFIC for the Identification of Plasma Diagnostic Biomarkers for Abdominal Aortic Aneurysm

BACKGROUND: Abdominal aortic aneurysm (AAA) is characterized by increased aortic vessel wall diameter (>1.5 times normal) and loss of parallelism. This disease is responsible for 1-4% mortality occurring on rupture in males older than 65 years. Due to its asymptomatic nature, proteomic techniques were used to search for diagnostic biomarkers that might allow surgical intervention under nonlife threatening conditions. METHODOLOGY/PRINCIPAL FINDINGS: Pooled human plasma samples of 17 AAA and 17 control patients were depleted of the most abundant proteins and compared using a data-independent shotgun proteomic strategy, Precursor Acquisition Independent From Ion Count (PAcIFIC), combined with spectral counting and isobaric tandem mass tags. Both quantitative methods collectively identified 80 proteins as statistically differentially abundant between AAA and control patients. Among differentially abundant proteins, a subgroup of 19 was selected according to Gene Ontology classification and implication in AAA for verification by Western blot (WB) in the same 34 individual plasma samples that comprised the pools. From the 19 proteins, 12 were detected by WB. Five of them were verified to be differentially up-regulated in individual plasma of AAA patients: adiponectin, extracellular superoxide dismutase, protein AMBP, kallistatin and carboxypeptidase B2. CONCLUSIONS/SIGNIFICANCE: Plasma depletion of high abundance proteins combined with quantitative PAcIFIC analysis offered an efficient and sensitive tool for the screening of new potential biomarkers of AAA. However, WB analysis to verify the 19 PAcIFIC identified proteins of interest proved inconclusive save for five proteins. We discuss these five in terms of their potential relevance as biological markers for use in AAA screening of population at risk

Combining bioinformatics and MS-based proteomics: clinical implications

Clinical proteomics research aims at i) discovery of protein biomarkers for screening, diagnosis and prognosis of disease, ii) discovery of protein therapeutic targets for improvement of disease prevention, treatment and follow-up, and iii) development of mass spectrometry (MS)-based assays that could be implemented in clinical chemistry, microbiology or hematology laboratories. MS has been increasingly applied in clinical proteomics studies for the identification and quantification of proteins. Bioinformatics plays a key role in the exploitation of MS data in several aspects such as the generation and curation of protein sequence databases, the development of appropriate software for MS data treatment and integration with other omics data and the establishment of adequate standard files for data sharing. In this article, we discuss the main MS approaches and bioinformatics solutions that are currently applied to accomplish the objectives of clinical proteomic research

Measurement of the double-differential inclusive jet cross section in proton-proton collisions at s\sqrt{s} = 5.02 TeV

International audienceThe inclusive jet cross section is measured as a function of jet transverse momentum $p_\mathrm{T}$ and rapidity $y$. The measurement is performed using proton-proton collision data at $\sqrt{s}$ = 5.02 TeV, recorded by the CMS experiment at the LHC, corresponding to an integrated luminosity of 27.4 pb$^{-1}$. The jets are reconstructed with the anti-$k_\mathrm{T}$ algorithm using a distance parameter of $R$ = 0.4, within the rapidity interval $\lvert y\rvert$$\lt$ 2, and across the kinematic range 0.06 $\lt$$p_\mathrm{T}$$\lt$ 1 TeV. The jet cross section is unfolded from detector to particle level using the determined jet response and resolution. The results are compared to predictions of perturbative quantum chromodynamics, calculated at both next-to-leading order and next-to-next-to-leading order. The predictions are corrected for nonperturbative effects, and presented for a variety of parton distribution functions and choices of the renormalization/factorization scales and the strong coupling $\alpha_\mathrm{S}$

Nonresonant central exclusive production of charged-hadron pairs in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceThe central exclusive production of charged-hadron pairs in pp collisions at a centre-of-mass energy of 13\TeV is examined, based on data collected in a special high-$\beta^*$ run of the LHC. The nonresonant continuum processes are studied with the invariant mass of the centrally produced two-pion system in the resonance-free region, $m_{\pi^+\pi^-}$$\lt$ 0.7 GeV or $m_{\pi^+\pi^-}$$\gt$ 1.8 GeV. Differential cross sections as functions of the azimuthal angle between the surviving protons, squared exchanged four-momenta, and $m_{\pi^+\pi^-}$ are measured in a wide region of scattered proton transverse momenta, between 0.2 and 0.8 GeV, and for pion rapidities $\lvert y\rvert$$\lt$ 2. A rich structure of interactions related to double-pomeron exchange is observed. A parabolic minimum in the distribution of the two-proton azimuthal angle is observed for the first time. It can be interpreted as an effect of additional pomeron exchanges between the protons from the interference between the bare and the rescattered amplitudes. After model tuning, various physical quantities are determined that are related to the pomeron cross section, proton-pomeron and meson-pomeron form factors, pomeron trajectory and intercept, and coefficients of diffractive eigenstates of the proton

Nonresonant central exclusive production of charged-hadron pairs in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceThe central exclusive production of charged-hadron pairs in pp collisions at a centre-of-mass energy of 13\TeV is examined, based on data collected in a special high-$\beta^*$ run of the LHC. The nonresonant continuum processes are studied with the invariant mass of the centrally produced two-pion system in the resonance-free region, $m_{\pi^+\pi^-}$$\lt$ 0.7 GeV or $m_{\pi^+\pi^-}$$\gt$ 1.8 GeV. Differential cross sections as functions of the azimuthal angle between the surviving protons, squared exchanged four-momenta, and $m_{\pi^+\pi^-}$ are measured in a wide region of scattered proton transverse momenta, between 0.2 and 0.8 GeV, and for pion rapidities $\lvert y\rvert$$\lt$ 2. A rich structure of interactions related to double-pomeron exchange is observed. A parabolic minimum in the distribution of the two-proton azimuthal angle is observed for the first time. It can be interpreted as an effect of additional pomeron exchanges between the protons from the interference between the bare and the rescattered amplitudes. After model tuning, various physical quantities are determined that are related to the pomeron cross section, proton-pomeron and meson-pomeron form factors, pomeron trajectory and intercept, and coefficients of diffractive eigenstates of the proton

Measurement of the double-differential inclusive jet cross section in proton-proton collisions at s\sqrt{s} = 5.02 TeV

International audienceThe inclusive jet cross section is measured as a function of jet transverse momentum $p_\mathrm{T}$ and rapidity $y$. The measurement is performed using proton-proton collision data at $\sqrt{s}$ = 5.02 TeV, recorded by the CMS experiment at the LHC, corresponding to an integrated luminosity of 27.4 pb$^{-1}$. The jets are reconstructed with the anti-$k_\mathrm{T}$ algorithm using a distance parameter of $R$ = 0.4, within the rapidity interval $\lvert y\rvert$$\lt$ 2, and across the kinematic range 0.06 $\lt$$p_\mathrm{T}$$\lt$ 1 TeV. The jet cross section is unfolded from detector to particle level using the determined jet response and resolution. The results are compared to predictions of perturbative quantum chromodynamics, calculated at both next-to-leading order and next-to-next-to-leading order. The predictions are corrected for nonperturbative effects, and presented for a variety of parton distribution functions and choices of the renormalization/factorization scales and the strong coupling $\alpha_\mathrm{S}$