| 1. |
- Romagnoni, A, et al.
(author)
-
Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data
- 2019
-
In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 10351-
-
Journal article (peer-reviewed)abstract
- Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identified using genome wide association studies (GWAS). However, the genetic architecture of the trait remains largely unknown. The recent development of machine learning (ML) approaches incited us to apply them to classify healthy and diseased people according to their genomic information. The Immunochip dataset containing 18,227 CD patients and 34,050 healthy controls enrolled and genotyped by the international Inflammatory Bowel Disease genetic consortium (IIBDGC) has been re-analyzed using a set of ML methods: penalized logistic regression (LR), gradient boosted trees (GBT) and artificial neural networks (NN). The main score used to compare the methods was the Area Under the ROC Curve (AUC) statistics. The impact of quality control (QC), imputing and coding methods on LR results showed that QC methods and imputation of missing genotypes may artificially increase the scores. At the opposite, neither the patient/control ratio nor marker preselection or coding strategies significantly affected the results. LR methods, including Lasso, Ridge and ElasticNet provided similar results with a maximum AUC of 0.80. GBT methods like XGBoost, LightGBM and CatBoost, together with dense NN with one or more hidden layers, provided similar AUC values, suggesting limited epistatic effects in the genetic architecture of the trait. ML methods detected near all the genetic variants previously identified by GWAS among the best predictors plus additional predictors with lower effects. The robustness and complementarity of the different methods are also studied. Compared to LR, non-linear models such as GBT or NN may provide robust complementary approaches to identify and classify genetic markers.
|
|
| 2. |
- Momozawa, Y, et al.
(author)
-
IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes
- 2018
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 2427-
-
Journal article (peer-reviewed)abstract
- GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach.
|
|
| 3. |
|
|
| 4. |
- Franke, Andre, et al.
(author)
-
Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci
- 2010
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1118-1125
-
Journal article (peer-reviewed)abstract
- We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10⁻⁸). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.
|
|
| 5. |
|
|
| 6. |
- Akiba, K., et al.
(author)
-
The LHCb VELO Upgrade module construction
- 2024
-
In: Journal of Instrumentation. - : Institute of Physics Publishing (IOPP). - 1748-0221. ; 19:6
-
Journal article (peer-reviewed)abstract
- The LHCb detector has undergone a major upgrade for LHC Run 3. This Upgrade I detector facilitates operation at higher luminosity and utilises full-detector information at the LHC collision rate, critically including the use of vertex information. A new vertex locator system, the VELO Upgrade, has been constructed. The core element of the new VELO are the double-sided pixelated hybrid silicon detector modules which operate in vacuum close to the LHC beam in a high radiation environment. The construction and quality assurance tests of these modules are described in this paper. The modules incorporate 200 mu m thick, n -on -p silicon sensors bump-bonded to 130 nm technology ASICs. These are attached with high precision to a silicon microchannel substrate that uses evaporative CO 2 cooling. The ASICs are controlled and read out with flexible printed circuits that are glued to the substrate and wire -bonded to the chips. The mechanical support of the module is given by a carbon fibre plate, two carbon fibre rods and an aluminium plate. The sensor attachment was achieved with an average precision of 21 mu m, more than 99.5% of all pixels are fully functional, and a thermal figure of merit of 3 Kcm 2 W - 1 was achieved. The production of the modules was successfully completed in 2021, with the final assembly and installation completed in time for data taking in 2022.
|
|
| 7. |
- Lourido, L., et al.
(author)
-
Circulating centromere protein F autoantibodies for predicting clinical response to infliximab in rheumatoid arthritis
- 2020
-
In: Annals of the Rheumatic Diseases. - : BMJ Publishing Group. - 0003-4967 .- 1468-2060. ; 79, s. 1399-1399
-
Journal article (other academic/artistic)abstract
- One third of patients with rheumatoid arthritis (RA) respond poorly to TNF inhibitors and related studies are inconsistent in predictive biomarkers. The identification of biomarkers that predict the treatment response prior to drug exposure is a current priority on the RA field. ACPA and RF are ubiquitously tested in RA patients, but other autoantibodies exist and may provide additional information on RA treatment response.Objectives:This study aimed to identify circulating autoantibodies for predicting response to infliximab (IFX) in RA.Methods:We profiled the autoantibody repertoire of baseline sera from 155 biologic naïve RA patients treated with IFX. The sera were provided by three independent clinical sources and distributed in one exploratory cohort (N=20) collected from Hospital Clínico Universitario of Santiago de Compostela (Spain), one replication cohort (N=61) collected from Hospital Universitario de A Coruña (Spain) and samples from the Swedish Farmacotherapy (SWEFOT) trial (Sweden) (N=74) for clinical validation. The presence of autoantibodies and their levels in serum were analysed in association with EULAR clinical response at 6 months follow-up: good response (GR, N=56), moderate (MR, N=55) and non-response (NR, N=44). A suspension bead array platform built on protein fragments within Human Protein Atlas and selected from an initial untargeted screening using an array containing 42000 antigens was employed to identify the IgG and IgA autoantibodies on the exploratory cohort. A replication and validation phases were carried out on the other two serum sample cohorts. Meta-analysis and Receiver Operating Curves were performed in order to assess the clinical relevance of the findings observed.Results:Meta-analysis revealed that the levels in serum of IgG autoantibodies against Centromere protein F (CENPF) are significantly increased in responders (good responders and moderate responders; N=111) to IFX compared to non-responders (N=44) (P=0.018). CENP-F is a proliferation-associated and cell cycle-dependent centromere autoantigen that might be involved in the increased or abnormal cell proliferation that occurs during RA process. The combination of the anti-CENPF antibodies with clinical variables (age, sex, DAS28-ESR) resulted in the best model to discriminate the patients that will respond to IFX, showing an AUC of 0.756 (95% CI [0.639-0.874], P=0.001).Conclusion:High serum levels of IgG anti-CENPF antibodies might be potentially useful to identify RA patients more likely to benefit from IFXDisclosure of Interests:Lucía Lourido: None declared, Cristina Ruiz-Romero: None declared, flor picchi: None declared, Naomi Diz-Rosales: None declared, Sergio Vilaboa-Galán: None declared, Carlos Fernández-López: None declared, Jose Antonio Pinto Tasende: None declared, Eva Perez-Pampin: None declared, Cristina Regueiro Expósito: None declared, ANTONIO MERA VARELA: None declared, Antonio Gonzalez: None declared, Karen Hambardzumyan: None declared, Saedis Saevarsdottir Employee of: Part-time at deCODE Genetics/Amgen Inc, working on genetic research unrelated to this project, Peter Nilsson: None declared, Francisco J. Blanco Grant/research support from: Sanofi-Aventis, Lilly, Bristol MS, Amgen, Pfizer, Abbvie, TRB Chemedica International, Glaxo SmithKline, Archigen Biotech Limited, Novartis, Nichi-iko pharmaceutical Co, Genentech, Jannsen Research & Development, UCB Biopharma, Centrexion Theurapeutics, Celgene, Roche, Regeneron Pharmaceuticals Inc, Biohope, Corbus Pharmaceutical, Tedec Meiji Pharma, Kiniksa Pharmaceuticals, Ltd, Gilead Sciences Inc, Consultant of: Lilly, Bristol MS, Pfizer
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Monteverde, M, et al.
(author)
-
Fluorinated Hg-1223 under pressure : the ultimate Tc of the cuprates?
- 2004
-
In: Physica. C, Superconductivity. - : Elsevier B.V. - 0921-4534 .- 1873-2143. ; 408-410, s. 23-24
-
Journal article (peer-reviewed)abstract
- High pressure experiments have revealed that Tc is affected by two main pressure-dependent parameters: the doping level of the CuO2 planes and by an intrinsic factor. The origin of the intrinsic factor is still unclear as, depending on the experiment, it is associated with the reduction of the c or the a lattice parameters. F incorporation into the Hg-1223 structure yields an enhancement of Tc up to a susceptibility onset of 138 K, mainly related to a compression of the a crystallographic axis. We have obtained a new high Tc record (166 K ± 1.5 K) by applying pressure (23 GPa) in the fluorinated Hg-1223 superconductor optimally doped. Tc increases with increasing pressure, reaching different maximum values, depending on the F doping level, and decreases for a further increase of pressure. This saturation of Tc may be the highest Tc that can be obtained for the cuprates, considering the particular structural characteristics of this system.
|
|
