| 1. |
- Romagnoni, A, et al.
(författare)
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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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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 10351-
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Tidskriftsartikel (refereegranskat)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. |
- Regev, A, et al.
(författare)
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The Human Cell Atlas
- 2017
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Ingår i: eLife. - : ELIFE SCIENCES PUBLICATIONS LTD. - 2050-084X. ; 6
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Gaulton, Kyle J, et al.
(författare)
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Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
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Tidskriftsartikel (refereegranskat)abstract
- We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
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| 4. |
- Tobin, J. J., et al.
(författare)
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A triple protostar system formed via fragmentation of a gravitationally unstable disk
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 538:7626, s. 483-
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Tidskriftsartikel (refereegranskat)abstract
- Binary and multiple star systems are a frequent outcome of the star formation process(1,2) and as a result almost half of all stars with masses similar to that of the Sun have at least one companion star(3). Theoretical studies indicate that there are two main pathways that can operate concurrently to form binary/multiple star systems: large-scale fragmentation of turbulent gas cores and filaments(4,5) or smaller-scale fragmentation of a massive protostellar disk due to gravitational instability(6,7). Observational evidence for turbulent fragmentation on scales of more than 1,000 astronomical units has recently emerged(8,9). Previous evidence for disk fragmentation was limited to inferences based on the separations of more-evolved pre-main sequence and protostellar multiple systems(10-13). The triple protostar system L1448 IRS3B is an ideal system with which to search for evidence of disk fragmentation as it is in an early phase of the star formation process, it is likely to be less than 150,000 years old(14) and all of the protostars in the system are separated by less than 200 astronomical units. Here we report observations of dust and molecular gas emission that reveal a disk with a spiral structure surrounding the three protostars. Two protostars near the centre of the disk are separated by 61 astronomical units and a tertiary protostar is coincident with a spiral arm in the outer disk at a separation of 183 astronomical units(13). The inferred mass of the central pair of protostellar objects is approximately one solar mass, while the disk surrounding the three protostars has a total mass of around 0.30 solar masses. The tertiary protostar itself has a minimum mass of about 0.085 solar masses. We demonstrate that the disk around L1448 IRS3B appears susceptible to disk fragmentation at radii between 150 and 320 astronomical units, overlapping with the location of the tertiary protostar. This is consistent with models for a protostellar disk that has recently undergone gravitational instability, spawning one or two companion stars.
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| 5. |
- Tobin, John J., et al.
(författare)
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The VLA/ALMA Nascent Disk and Multiplicity (VANDAM) Survey of Orion Protostars. I. Identifying and Characterizing the Protostellar Content of the OMC-2 FIR4 and OMC-2 FIR3 Regions
- 2019
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 886:1
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Tidskriftsartikel (refereegranskat)abstract
- We present Atacama Large Millimeter/submillimeter Array (0.87 mm) and Very Large Array (9 mm) observations toward OMC-2 FIR4 and OMC-2 FIR3 within the Orion integral-shaped filament, thought to be two of the nearest regions of intermediate-mass star formation. We characterize the continuum sources within these regions on ?40 au (01) scales and associated molecular line emission at a factor of ?30 better resolution than previous observations at similar wavelengths. We identify six compact continuum sources within OMC-2 FIR4, four in OMC-2 FIR3, and one additional source just outside OMC-2 FIR4. This continuum emission is tracing the inner envelope and/or disk emission on less than 100 au scales. HOPS-108 is the only protostar in OMC-2 FIR4 that exhibits emission from high-excitation transitions of complex organic molecules (e.g., methanol and other lines) coincident with the continuum emission. HOPS-370 in OMC-2 FIR3, with L;?;360 L, also exhibits emission from high-excitation methanol and other lines. The methanol emission toward these two protostars is indicative of temperatures high enough to thermally evaporate it from icy dust grains; overall, these protostars have characteristics similar to hot corinos. We do not identify a clear outflow from HOPS-108 in (CO)-C-12, but we find evidence of interaction between the outflow/jet from HOPS-370 and the OMC-2 FIR4 region. A multitude of observational constraints indicate that HOPS-108 is likely a low- to intermediate-mass protostar in its main mass accretion phase and is the most luminous protostar in OMC-2 FIR4. The high-resolution data presented here are essential for disentangling the embedded protostars from their surrounding dusty environments and characterizing them.
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