| 1. |
- Abelev, Betty, et al.
(författare)
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Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :7
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Tidskriftsartikel (refereegranskat)abstract
- We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
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| 2. |
- Abelev, Betty, et al.
(författare)
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Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
- 2013
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
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Tidskriftsartikel (refereegranskat)abstract
- Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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| 3. |
- Abelev, Betty, et al.
(författare)
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Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :11
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Tidskriftsartikel (refereegranskat)abstract
- The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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| 4. |
- Simonetti, Michele
(författare)
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Developing methods for mapping genetic heterogeneity in tumors : from bulk to single-cell resolution
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Tumors are complex ecosystems composed of billions of cells that constantly evolve over time. Intra-tumor heterogeneity (ITH) represents the diversity of this complex environment quantifiable both at the genetic and phenotypic level. Recently, next-generation sequencing (NGS) costs have dropped and NGS has become the standard tool for studying ITH. Moreover, advances in single-cell sequencing technologies allow studying tumor composition, evolution, and alterations at unprecedented scale and resolution. Besides the extreme importance of NGS technologies in cancer biology, their versatility has also played a pivotal role in the SARS-CoV-2 pandemic that started at the end of 2019. Indeed, thanks to NGS technologies, thousands of SARS-CoV-2 genomes have been sequenced worldwide enabling phylogenetic reconstruction of the spread and evolution of the virus. Furthermore, NGS techniques are currently used for genomic surveillance of the virus, which includes tracing the emergence of new viral variants that can potentially reduce the susceptibility to the newly developed vaccines. In paper I, we developed CUTseq, a reduced representation genome sequencing method that can be used to tag and amplify low-input genomic deoxyribonucleic acid (gDNA) samples to generate multiplexed NGS libraries. The method enables reproducible calling of copy number alterations (CNAs) gDNA extracted from cell lines and formalin-fixed paraffinembedded (FFPE) tissue specimens. We used CUTseq to assess genetic ITH by profiling multiple regions of individual FFPE sections of primary and metastatic breast cancer lesions. Finally, we developed a rapid and cost-effective version of CUTseq that allows highthroughput preparation of NGS libraries using a contactless liquid-dispensing robot. In paper II, we developed single-cell CUTseq (scCUTseq), an NGS method that builds on the design of CUTseq from paper I and includes a whole-genome amplification (WGA) step upfront to amplify gDNA from single cells. We leveraged on the nanodispensing device used in paper I to reduce the volume of reactions to nanoliters, which lowers reagent costs and scales up the number of cells that can be processed in parallel. The scalability of scCUTseq was demonstrated on cell lines, showing no difference between live and fixed samples. To assess the sensitivity of the method, we detected a 7 megabase (Mb) deletion induced by CRISPR/Cas9 occurring at low frequency (4.5%) in human TK6 lymphoblastoid cells. Finally, we applied the method to build a spatially resolved single-cell ITH atlas of CNAs in two prostate cancers. In paper III, we developed COVseq, a versatile and cost-effective NGS method that can be used to prepare multiplexed libraries from dozens of SARS-CoV-2 ribonucleic acid (RNA) samples in parallel using the approaches described in paper I and II. The method was first benchmarked with a commercial kit showing high correlation of breadth of coverage and single-nucleotide variants (SNVs) detection. To demonstrate the reproducibility of the method, COVseq was applied to 274 diagnostic samples enabling the detection of the UK variant of concern B.1.1.7. Finally, a comparative cost analysis showed that COVseq can reduce the preparation and sequencing costs to ~$20 per sample.
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| 5. |
- Wu, Chenglin, et al.
(författare)
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RollFISH achieves robust quantification of single-molecule RNA biomarkers in paraffin-embedded tumor tissue samples
- 2018
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 1
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Tidskriftsartikel (refereegranskat)abstract
- Single-molecule RNA fluorescence in situ hybridization (smFISH) represents a promising approach to quantify the expression of clinically useful biomarkers in tumor samples. However, routine application of smFISH to formalin-fixed, paraffin-embedded (FFPE) samples is challenging due to the low signal intensity and high background noise. Here we present RollFISH, a method combining the specificity of smFISH with the signal boosting of rolling circle amplification. We apply RollFISH to quantify widely used breast cancer biomarkers in cell lines and FFPE samples. Thanks to the high signal-to-noise ratio, we can visualize selected biomarkers at low magnification (20 x) across entire tissue sections, and thus assess their spatial heterogeneity. Lastly, we apply RollFISH to quantify HER2 mRNA in 150 samples on a single tissue microarray, achieving a sensitivity and specificity of detection of HER2-positive samples of similar to 90%. RollFISH is a robust method for quantifying the expression and intratumor heterogeneity of biomarkers in FFPE tissues.
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| 6. |
- Zerdes, Ioannis, et al.
(författare)
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Interplay between copy number alterations and immune profiles in the early breast cancer Scandinavian Breast Group 2004-1 randomized phase II trial : results from a feasibility study
- 2021
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Ingår i: npj Breast Cancer. - : Springer Nature. - 2374-4677. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Emerging data indicate that genomic alterations can shape immune cell composition in early breast cancer. However, there is a need for complementary imaging and sequencing methods for the quantitative assessment of combined somatic copy number alteration (SCNA) and immune profiling in pathological samples. Here, we tested the feasibility of three approaches-CUTseq, for high-throughput low-input SCNA profiling, multiplexed fluorescent immunohistochemistry (mfIHC) and digital-image analysis (DIA) for quantitative immuno-profiling- in archival formalin-fixed paraffin-embedded (FFPE) tissue samples from patients enrolled in the randomized SBG-2004-1 phase II trial. CUTseq was able to reproducibly identify amplification and deletion events with a resolution of 100 kb using only 6 ng of DNA extracted from FFPE tissue and pooling together 77 samples into the same sequencing library. In the same samples, mfIHC revealed that CD4 + T-cells and CD68 + macrophages were the most abundant immune cells and they mostly expressed PD-L1 and PD-1. Combined analysis showed that the SCNA burden was inversely associated with lymphocytic infiltration. Our results set the basis for further applications of CUTseq, mfIHC and DIA to larger cohorts of early breast cancer patients.
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