The potential of a data centred approach & knowledge graph data representation in chemical safety and drug design

Big Data pervades nearly all areas of life sciences, yet the analysis of large integrated data sets remains a major challenge. Moreover, the field of life sciences is highly fragmented and, consequently, so is its data, knowledge, and standards. This, in turn, makes integrated data analysis and knowledge gathering across sub-fields a demanding task. At the same time, the integration of various research angles and data types is crucial for modelling the complexity of organisms and biological processes in a holistic manner. This is especially valid in the context of drug development and chemical safety assessment where computational methods can provide solutions for the urgent need of fast, effective, and sustainable approaches. At the same time, such computational methods require the development of methodologies suitable for an inte-grated and data centred Big Data view. Here we discuss Knowledge Graphs (KG) as a solution to a data centred analysis approach for drug and chemical development and safety assessment. KGs are knowledge bases, data analysis engines, and knowledge discovery systems all in one, allowing them to be used from simple data retrieval, over meta-analysis to complex predictive and knowledge discovery systems. Therefore, KGs have immense potential to advance the data centred approach, the re-usability, and infor-mativity of data. Furthermore, they can improve the power of analysis, and the complexity of modelled processes, all while providing knowledge in a natively human understandable network data model. (c) 2022 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY-NC-ND license (http://creative-commons.org/licenses/by-nc-nd/4.0/).Peer reviewe

Toxicogenomics analysis of dynamic dose-response in macrophages highlights molecular alterations relevant for multi-walled carbon nanotube-induced lung fibrosis

Toxicogenomics approaches are increasingly used to gain mechanistic insight into the toxicity of engineered nanomaterials (ENMs). These emerging technologies have been shown to aid the translation of in vitro experimentation into relevant information on real-life exposures. Furthermore, integrating multiple layers of molecular alteration can provide a broader understanding of the toxicological insult. While there is growing evidence of the immunotoxic effects of several ENMs, the mechanisms are less characterized, and the dynamics of the molecular adaptation of the immune cells are still largely unknown. Here, we hypothesized that a multi-omics investigation of dynamic dose-dependent (DDD) molecular alterations could be used to retrieve relevant information concerning possible long-term consequences of the exposure. To this end, we applied this approach on a model of human macrophages to investigate the effects of rigid multi-walled carbon nanotubes (rCNTs). THP-1 macrophages were exposed to increasing concentrations of rCNTs and the genome-wide transcription and gene promoter methylation were assessed at three consecutive time points. The results suggest dynamic molecular adaptation with a rapid response in the gene expression and contribution of DNA methylation in the long-term adaptation. Moreover, our analytical approach is able to highlight patterns of molecular alteration in vitro that are relevant for the pathogenesis of pulmonary fibrosis, a known long-term effect of rCNTs exposure in vivo.Peer reviewe

Prompt D-0, D+, and D*(+) production in Pb-Pb collisions at root S-NN=5.02 TeV

The production of prompt D-0, D+, and D*(+) mesons was measured at midrapidity (vertical bar y vertical bar < 0.5) in Pb-Pb collisions at the centre-of-mass energy per nucleon-nucleon pair root S-NN = 5.02 TeV with the ALICE detector at the LHC. The D mesons were reconstructed via their hadronic decay channels and their production yields were measured in central (0-10%) and semicentral (30-50%) collisions. The measurement was performed up to a transverse momentum (p(T)) of 36 or 50 GeV/c depending on the D meson species and the centrality interval. For the first time in Pb-Pb collisions at the LHC, the yield of D-0 mesons was measured down to p(T) = 0, which allowed a model-independent determination of the p(T)-integrated yield per unit of rapidity (dN/dy). A maximum suppression by a factor 5 and 2.5 was observed with the nuclear modification factor (R-AA) of prompt D mesons at p(T) = 6-8 GeV/c for the 0-10% and 30-50% centrality classes, respectively. The D-meson R-AA is compared with that of charged pions, charged hadrons, and J/psi mesons as well as with theoretical predictions. The analysis of the agreement between the measured R-AA, elliptic (v(2)) and triangular (v(3)) flow, and the model predictions allowed us to constrain the charm spatial diffusion coefficient D-s. Furthermore the comparison of R-AA and v(2) with different implementations of the same models provides an important insight into the role of radiative energy loss as well as charm quark recombination in the hadronisation mechanisms.Peer reviewe

Forward rapidity J/psi production as a function of charged-particle multiplicity in pp collisions at root s=5.02 and 13 TeV

The production of J/psi is measured as a function of charged-particle multiplicity at forward rapidity in proton-proton (pp) collisions at center-of-mass energies root s = 5.02 and 13 TeV. The J/psi mesons are reconstructed via their decay into dimuons in the rapidity interval (2.5 ), at both the colliding energies. Measurements are compared with available ALICE results at midrapidity and theoretical model calculations. First measurement of the mean transverse momentum () of J/psi in pp collisions exhibits an increasing trend as a function of dN(ch)/d eta/ showing a saturation towards high charged-particle multiplicities.Peer reviewe

Observation of a multiplicity dependence in the p(T)-differential charm baryon-to-meson ratios in proton-proton collisions at root s=13 TeV

The production of prompt D-0, D-s(+) and Lambda(+)(c) hadrons, and their ratios, D-s(+)/D-0 and Lambda(+)(c)/D-0, are measured in proton-proton collisions at root s = 13 TeV at midrapidity (vertical bar y vertical bar < 0.5) with the ALICE detector at the LHC. The measurements are performed as a function of the charm-hadron transverse momentum (p(T)) in intervals of charged-particle multiplicity, measured with two multiplicity estimators covering different pseudorapidity regions. While the strange to non-strange D-s(+)/D-0 ratio indicates no significant multiplicity dependence, the baryon-to-meson P-T-differential Lambda(+)(c)/D-0 ratio shows a multiplicity-dependent enhancement, with a significance of 5.3 sigma for 1 < p(T) < 12 GeV/c, comparing the highest multiplicity interval with respect to the lowest one. The measurements are compared with a theoretical model that explains the multiplicity dependence by a canonical treatment of quantum charges in the statistical hadronisation approach, and with predictions from event generators that implement colour reconnection mechanisms beyond the leading colour approximation to model the hadronisation process. The Lambda(+)(c)/D-0 ratios as a function of p(T) present a similar shape and magnitude as the Lambda/K-s(0) ratios in comparable multiplicity intervals, suggesting a potential common mechanism for light- and charmhadron formation, with analogous multiplicity dependence. The p(T)-integrated ratios, extrapolated down to p(T) = 0, do not show a significant dependence on multiplicity within the uncertainties. (C) 2022 European Organization for Nuclear Research. Published by Elsevier B.V.Peer reviewe

Measurement of inclusive charged-particle b-jet production in pp and p-Pb collisions at root S-NN =5.02 TeV

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Measurement of prompt D-s(+)-meson production and azimuthal anisotropy in Pb-Pb collisions at root s(NN)=5.02 TeV

The production yield and angular anisotropy of prompt D-s(+) mesons were measured as a function of transverse momentum (p(T)) in Pb-Pb collisions at a centre-of-mass energy per nucleon pair root s(NN) = 5.02 TeV collected with the ALICE detector at the LHC. D-s(+) mesons and their charge conjugates were reconstructed at midrapidity (vertical bar y vertical bar phi pi(+), with phi -> K-K+, in the p(T) intervals 2 10 GeV/c, the measured D-s(+)-meson nuclear modification factor R-AA is consistent with the one of non-strange D mesons within uncertainties, while at lower p(T) a hint for a D-s(+)-meson R-AA larger than that of non-strange D mesons is seen. The enhanced production of D-s(+) relative to non-strange D mesons is also studied by comparing the p(T)-dependent D-s(+)/D-0 production yield ratios in Pb-Pb and in pp collisions. The ratio measured in Pb-Pb collisions is found to be on average higher than that in pp collisions in the interval 2 < p(T) < 8 GeV/c with a significance of 2.3 sigma and 2.4 sigma for the 0-10% and 30-50% centrality intervals. The azimuthal anisotropy coefficient v(2) of prompt D-s(+) mesons was measured in Pb-Pb collisions in the 30-50% centrality interval and is found to be compatible with that of non-strange D mesons. The main features of the measured R-AA, D-s(+)/D-0 ratio, and v(2) as a function of p(T) are described by theoretical calculations of charm-quark transport in a hydrodynamically expanding quark-gluon plasma including hadronisation via charm-quark recombination with light quarks from the medium. The p(T)-integrated production yield of D-s(+) mesons is compatible with the prediction of the statistical hadronisation model. (c) 2022 European Organization for Nuclear Research, ALICE. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Funded by SCOAP(3).Peer reviewe

Characterizing the initial conditions of heavy-ion collisions at the LHC with mean transverse momentum and anisotropic flow correlations

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General balance functions of identified charged hadron pairs of (pi, K, p) in Pb-Pb collisions at root s(NN)=2.76 TeV

First measurements of balance functions (BFs) of all combinations of identified charged hadron (pi, K, p) pairs in Pb-Pb collisions at root s(NN) = 2.76 TeV recorded by the ALICE detector are presented. The BF measurements are carried out as two-dimensional differential correlators versus the relative rapidity (Delta y) and azimuthal angle (Delta phi) of hadron pairs, and studied as a function of collision centrality. The Delta phi dependence of BFs is expected to be sensitive to the light quark diffusivity in the quark-gluon plasma. While the BF azimuthal widths of all pairs substantially decrease from peripheral to central collisions, the longitudinal widths exhibit mixed behaviors: BFs of pi pi and cross-species pairs narrow significantly in more central collisions, whereas those of KK and pp are found to be independent of collision centrality. This dichotomy is qualitatively consistent with the presence of strong radial flow effects and the existence of two stages of quark production in relativistic heavy-ion collisions. Finally, the first measurements of the collision centrality evolution of BF integrals are presented, with the observation that charge balancing fractions are nearly independent of collision centrality in Pb-Pb collisions. Overall, the results presented provide new and challenging constraints for theoretical models of hadron production and transport in relativistic heavy-ion collisions. (C) 2022 European Organization for Nuclear Research, ALICE. Published by Elsevier B.V.Peer reviewe

KS0KS0 and KS0K± femtoscopy in pp collisions at s=5.02 and 13 TeV

Femtoscopic correlations with the particle pair combinations (KSKS0)-K-0 and (KSK +/-)-K-0 are studied in pp collisions at root s= 5.02 and 13 TeV by the ALICE experiment. At both energies, boson source parameters are extracted for both pair combinations, by fitting models based on Gaussian size distributions of the sources, to the measured two-particle correlation functions. The interaction model used for the (KSKS0)-K-0 analysis includes quantum statistics and strong final-state interactions through the f(0) (980) and a(0) (980) resonances. The model used for the (KSK +/-)-K-0 analysis includes only the final-state interaction through the a(0) resonance. Source parameters extracted in the present work are compared with published values from pp collisions at root s = 7 TeV and the different pair combinations are found to be consistent. From the observation that the strength of the (KSKS0)-K-0 correlations is significantly greater than the strength of the (KSK +/-)-K-0 correlations, the new results are compatible with the a(0) resonance being a tetraquark state of the form (q(1), (q(2)) over bar, s, (s) over bar), where q(1) and q(2) are uor d quarks. (C) 2022 European Organization for Nuclear Research, ALICE. Published by Elsevier B.V.Peer reviewe