| 1. |
- Romagnoni, A, et al.
(author)
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Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data
- 2019
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 10351-
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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.
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| 2. |
- Barnett, R., et al.
(author)
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Euclid preparation V. Predicted yield of redshift 7 < z < 9 quasars from the wide survey
- 2019
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 631
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Journal article (peer-reviewed)abstract
- We provide predictions of the yield of 7 < z < 9 quasars from the Euclid wide survey, updating the calculation presented in the Euclid Red Book in several ways. We account for revisions to the Euclid near-infrared filter wavelengths; we adopt steeper rates of decline of the quasar luminosity function (QLF; Phi) with redshift, Phi proportional to 10(k(z-6)), k = 0:72, and a further steeper rate of decline, k = 0:92; we use better models of the contaminating populations (MLT dwarfs and compact early-type galaxies); and we make use of an improved Bayesian selection method, compared to the colour cuts used for the Red Book calculation, allowing the identification of fainter quasars, down to J(AB) similar to 23. Quasars at z > 8 may be selected from Euclid OYJH photometry alone, but selection over the redshift interval 7 < z < 8 is greatly improved by the addition of z-band data from, e.g., Pan-STARRS and LSST. We calculate predicted quasar yields for the assumed values of the rate of decline of the QLF beyond z = 6. If the decline of the QLF accelerates beyond z = 6, with k = 0.92, Euclid should nevertheless find over 100 quasars with 7.0 < z < 7.5, and similar to 25 quasars beyond the current record of z = 7.5, including similar to 8 beyond z = 8.0. The first Euclid quasars at z > 7.5 should be found in the DR1 data release, expected in 2024. It will be possible to determine the bright-end slope of the QLF, 7 < z < 8, M-1450 < 25, using 8m class telescopes to confirm candidates, but follow-up with JWST or E-ELT will be required to measure the faint-end slope. Contamination of the candidate lists is predicted to be modest even at J(AB) similar to 23. The precision with which k can be determined over 7 < z < 8 depends on the value of k, but assuming k = 0.72 it can be measured to a 1 sigma uncertainty of 0.07.
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| 3. |
- Momozawa, Y, et al.
(author)
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IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes
- 2018
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 2427-
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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.
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| 4. |
- Amendola, L., et al.
(author)
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Cosmology and fundamental physics with the Euclid satellite
- 2018
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In: Living Reviews in Relativity. - : Springer. - 1433-8351 .- 2367-3613. ; 21:1
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Journal article (peer-reviewed)abstract
- Euclid is a European Space Agency medium-class mission selected for launch in 2020 within the cosmic vision 2015–2025 program. The main goal of Euclid is to understand the origin of the accelerated expansion of the universe. Euclid will explore the expansion history of the universe and the evolution of cosmic structures by measuring shapes and red-shifts of galaxies as well as the distribution of clusters of galaxies over a large fraction of the sky. Although the main driver for Euclid is the nature of dark energy, Euclid science covers a vast range of topics, from cosmology to galaxy evolution to planetary research. In this review we focus on cosmology and fundamental physics, with a strong emphasis on science beyond the current standard models. We discuss five broad topics: dark energy and modified gravity, dark matter, initial conditions, basic assumptions and questions of methodology in the data analysis. This review has been planned and carried out within Euclid’s Theory Working Group and is meant to provide a guide to the scientific themes that will underlie the activity of the group during the preparation of the Euclid mission.
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| 7. |
- Martin, Neil E, et al.
(author)
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Defining a Standard Set of Patient-centered Outcomes for Men with Localized Prostate Cancer
- 2015
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In: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 67:3, s. 460-467
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Journal article (peer-reviewed)abstract
- BACKGROUND: Value-based health care has been proposed as a unifying force to drive improved outcomes and cost containment.OBJECTIVE: To develop a standard set of multidimensional patient-centered health outcomes for tracking, comparing, and improving localized prostate cancer (PCa) treatment value.DESIGN, SETTING, AND PARTICIPANTS: We convened an international working group of patients, registry experts, urologists, and radiation oncologists to review existing data and practices.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The group defined a recommended standard set representing who should be tracked, what should be measured and at what time points, and what data are necessary to make meaningful comparisons. Using a modified Delphi method over a series of teleconferences, the group reached consensus for the Standard Set.RESULTS AND LIMITATIONS: We recommend that the Standard Set apply to men with newly diagnosed localized PCa treated with active surveillance, surgery, radiation, or other methods. The Standard Set includes acute toxicities occurring within 6 mo of treatment as well as patient-reported outcomes tracked regularly out to 10 yr. Patient-reported domains of urinary incontinence and irritation, bowel symptoms, sexual symptoms, and hormonal symptoms are included, and the recommended measurement tool is the Expanded Prostate Cancer Index Composite Short Form. Disease control outcomes include overall, cause-specific, metastasis-free, and biochemical relapse-free survival. Baseline clinical, pathologic, and comorbidity information is included to improve the interpretability of comparisons.CONCLUSIONS: We have defined a simple, easily implemented set of outcomes that we believe should be measured in all men with localized PCa as a crucial first step in improving the value of care.PATIENT SUMMARY: Measuring, reporting, and comparing identical outcomes across treatments and treatment centers will provide patients and providers with information to make informed treatment decisions. We defined a set of outcomes that we recommend being tracked for every man being treated for localized prostate cancer.
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| 8. |
- Orgel, Csilla, et al.
(author)
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Gridmapping the Northern Plains of Mars: A New Overview of Recent Water‐ and Ice‐Related Landforms in Acidalia Planitia.
- 2019
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In: Journal of Geophysical Research - Planets. - 2169-9100. ; 124:2, s. 454-82
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Journal article (peer-reviewed)abstract
- We used a grid‐mapping technique to analyze the distribution of 13 water‐ and ice‐related landforms in Acidalia Planitia as part of a joint effort to study the three main basins in the northern lowlands of Mars, that is, Acidalia, Utopia, and Arcadia Planitiae. The landforms were mapped at full Context Camera resolution along a 300‐km‐wide strip from 20°N to 84°N. We identified four landform assemblages: (1) Geologically recent polar cap (massive ice), which superposes the latitude‐dependent mantle (LDM) (LA1); (2) ice‐related landforms, such as LDM, textured terrain, small‐scale polygons, scalloped terrain, large‐scale viscous flow features, and gullies, which have an overlapping distribution (LA2); (3) surface features possibly related to water and subsurface sediment mobilization (LA3; kilometer‐scale polygons, large pitted mounds, small pitted mounds, thumbprint terrain); and (4) irregularly shaped pits with raised rims on equator‐facing slopes. Pits are likely the result of an energetic release of volatiles (H2O, CO2, and CH4), rather than impact‐, volcanism‐, or wind‐related processes. LDM occurs ubiquitously from 44°N to 78°N in Acidalia Planitia. Various observations suggest an origin of air fall deposition of LDM, which contains less ice in the uppermost tens of meters in Acidalia Planitia than in Arcadia and Utopia Planitiae. However, LDM may be thicker and more extended in the past in Acidalia Planitia. The transition between LDM‐free terrain and LDM is situated further north than in Utopia and Arcadia Planitiae, suggesting different past and/or present climatic conditions among the main basins in the northern lowlands.
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| 9. |
- Ramsdale, Jason D., et al.
(author)
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Gridmapping the northern plains of Mars: Geomorphological, Radar and Water-Equivalent Hydrogen results from Arcadia Plantia.
- 2019
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In: Journal of Geophysical Research - Planets. - 2169-9100. ; 124:2, s. 504-27
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Journal article (peer-reviewed)abstract
- A project of mapping ice‐related landforms was undertaken to understand the role of subsurface ice in the northern plains. This work is the first continuous regional mapping from CTX (ConTeXt Camera, 6 m/pixel; Malin et al., 2007) imagery in Arcadia Planitia along a strip 300 km across stretching from 30°N to 80°N centered on the 170°W line of longitude. The distribution and morphotypes of these landforms were used to understand the permafrost cryolithology. The mantled and textured signatures occur almost ubiquitously between 35°N and 78°N and have a positive spatial correlation with inferred ice stability based on thermal modeling, neutron spectroscopy, and radar data. The degradational features into the LDM (latitude‐dependent mantle) include pits, scallops, and 100‐m polygons and provide supporting evidence for subsurface ice and volatile loss between 35 and 70°N in Arcadia with the mantle between 70 and 78°N appearing much more intact. Pitted terrain appears to be much more pervasive in Arcadia than in Acidalia and Utopia suggesting that the Arcadia study area had more widespread near‐surface subsurface ice and thus was more susceptible to pitting or that the ice was less well buried by sediments. Correlations with ice stability models suggest that lack of pits north of 65–70°N could indicate a relatively young age (~1 Ma); however, this could also be explained through regional variations in degradation rates. The deposition of the LDM is consistent with an air fall hypothesis; however, there appears to be substantial evidence for fluvial processes in southern Arcadia with older, underlying processes being equally dominant with the LDM and degradation thereof in shaping the landscape.
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| 10. |
- Slaats, D., et al.
(author)
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Donor and Recipient Perspectives on Anonymity in Kidney Donation From Live Donors: A Multicenter Survey Study
- 2018
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In: American Journal of Kidney Diseases. - : Elsevier BV. - 0272-6386. ; 71:1, s. 52-64
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Journal article (peer-reviewed)abstract
- Background: Maintaining anonymity is a requirement in the Netherlands and Sweden for kidney donation from live donors in the context of nondirected (or unspecified) and paired exchange (or specified indirect) donation. Despite this policy, some donors and recipients express the desire to know one another. Little empirical evidence informs the debate on anonymity. This study explored the experiences, preferences, and attitudes of donors and recipients toward anonymity. Study Design: Retrospective observational multicenter study using both qualitative and quantitative methods. Setting & Participants: 414 participants from Dutch and Swedish transplantation centers who received or donated a kidney anonymously (nondirected or paired exchange) completed a questionnaire about anonymity. Participation was a median of 31 months after surgery. Factors: Country of residence, donor/recipient status, transplant type, time since surgery. Results: Most participants were satisfied with their experience of anonymity before and aftersurgery. A minority would have liked to have met the other party before (donors, 7%; recipients, 15%) or after (donors, 22%; recipients, 31%) surgery. Significantly more recipients than donors wanted to meet the other party. Most study participants were open to meeting the other party if the desire was mutual (donors, 58%; recipients, 60%). Donors agree significantly more with the principle of anonymity before and after surgery than recipients. Donors and recipients thought that if both parties agreed, it should be permissible to meet before or after surgery. There were few associations between country or time since surgery and experiences or attitudes. The pros and cons of anonymity reported by participants were clustered into relational and emotional, ethical, and practical and logistical domains. Limitations: The relatively low response rate of recipients may have reduced generalizability. Recall bias was possible given the time lag between transplantation and data collection. Conclusions: This exploratory study illustrated that although donors and recipients were usually satisfied with anonymity, the majority viewed a strict policy on anonymity as unnecessary. These results may inform policy and education on anonymity.
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