| 1. |
- Bar, N., et al.
(författare)
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A reference map of potential determinants for the human serum metabolome
- 2020
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Ingår i: Nature. - : Nature Research. - 0028-0836 .- 1476-4687. ; 588:7836, s. 135-140
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Tidskriftsartikel (refereegranskat)abstract
- The serum metabolome contains a plethora of biomarkers and causative agents of various diseases, some of which are endogenously produced and some that have been taken up from the environment1. The origins of specific compounds are known, including metabolites that are highly heritable2,3, or those that are influenced by the gut microbiome4, by lifestyle choices such as smoking5, or by diet6. However, the key determinants of most metabolites are still poorly understood. Here we measured the levels of 1,251 metabolites in serum samples from a unique and deeply phenotyped healthy human cohort of 491 individuals. We applied machine-learning algorithms to predict metabolite levels in held-out individuals on the basis of host genetics, gut microbiome, clinical parameters, diet, lifestyle and anthropometric measurements, and obtained statistically significant predictions for more than 76% of the profiled metabolites. Diet and microbiome had the strongest predictive power, and each explained hundreds of metabolites—in some cases, explaining more than 50% of the observed variance. We further validated microbiome-related predictions by showing a high replication rate in two geographically independent cohorts7,8 that were not available to us when we trained the algorithms. We used feature attribution analysis9 to reveal specific dietary and bacterial interactions. We further demonstrate that some of these interactions might be causal, as some metabolites that we predicted to be positively associated with bread were found to increase after a randomized clinical trial of bread intervention. Overall, our results reveal potential determinants of more than 800 metabolites, paving the way towards a mechanistic understanding of alterations in metabolites under different conditions and to designing interventions for manipulating the levels of circulating metabolites.
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| 2. |
- Wilman, H. R., et al.
(författare)
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Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration
- 2019
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Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 71:3, s. 594-602
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Excess liver iron content is common and is linked to the risk of hepatic and extrahepatic diseases. We aimed to identify genetic variants influencing liver iron content and use genetics to understand its link to other traits and diseases. Methods: First, we performed a genome-wide association study (GWAS) in 8,289 individuals from UK Biobank, whose liver iron level had been quantified by magnetic resonance imaging, before validating our findings in an independent cohort (n = 1,513 from IMI DIRECT). Second, we used Mendelian randomisation to test the causal effects of 25 predominantly metabolic traits on liver iron content. Third, we tested phenome-wide associations between liver iron variants and 770 traits and disease outcomes. Results: We identified 3 independent genetic variants (rs1800562 [C282Y] and rs1799945 [H63D] in HFE and rs855791 [V736A] in TMPRSS6) associated with liver iron content that reached the GWAS significance threshold (p <5 × 10−8). The 2 HFE variants account for ∼85% of all cases of hereditary haemochromatosis. Mendelian randomisation analysis provided evidence that higher central obesity plays a causal role in increased liver iron content. Phenome-wide association analysis demonstrated shared aetiopathogenic mechanisms for elevated liver iron, high blood pressure, cirrhosis, malignancies, neuropsychiatric and rheumatological conditions, while also highlighting inverse associations with anaemias, lipidaemias and ischaemic heart disease. Conclusion: Our study provides genetic evidence that mechanisms underlying higher liver iron content are likely systemic rather than organ specific, that higher central obesity is causally associated with higher liver iron, and that liver iron shares common aetiology with multiple metabolic and non-metabolic diseases. Lay summary: Excess liver iron content is common and is associated with liver diseases and metabolic diseases including diabetes, high blood pressure, and heart disease. We identified 3 genetic variants that are linked to an increased risk of developing higher liver iron content. We show that the same genetic variants are linked to higher risk of many diseases, but they may also be associated with some health advantages. Finally, we use genetic variants associated with waist-to-hip ratio as a tool to show that central obesity is causally associated with increased liver iron content.
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| 3. |
- Baldi, R. D., et al.
(författare)
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LeMMINGs III. The e-MERLIN legacy survey of the Palomar sample: Exploring the origin of nuclear radio emission in active and inactive galaxies through the [O iii] - Radio connection
- 2021
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 508:2, s. 2019-2038
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Tidskriftsartikel (refereegranskat)abstract
- What determines the nuclear radio emission in local galaxies? To address this question, we combine optical [O iii] line emission, robust black hole (BH) mass estimates, and high-resolution e-MERLIN 1.5-GHz data, from the LeMMINGs survey, of a statistically complete sample of 280 nearby optically active (LINER and Seyfert) and inactive [H ii and absorption line galaxies (ALGs)] galaxies. Using [O iii] luminosity (L[O III]) as a proxy for the accretion power, local galaxies follow distinct sequences in the optical-radio planes of BH activity, which suggest different origins of the nuclear radio emission for the optical classes. The 1.5-GHz radio luminosity of their parsec-scale cores (Lcore) is found to scale with BH mass (MBH) and [O iii] luminosity. Below MBH ∼106.5 M⊙, stellar processes from non-jetted H ii galaxies dominate with Lcore ∝ MBH0.61 ± 0.33 and Lcore ∝ L[O III]0.79 ± 0.30. Above MBH ∼106.5 M⊙, accretion-driven processes dominate with Lcore ∝ MBH1.5-1.65 and Lcore ∝ L[O III]0.99-1.31 for active galaxies: radio-quiet/loud LINERs, Seyferts, and jetted H ii galaxies always display (although low) signatures of radio-emitting BH activity, with L1.5 GHz ≳ 1019.8 W Hz-1 and MBH ≳ 107 M⊙, on a broad range of Eddington-scaled accretion rates (m). Radio-quiet and radio-loud LINERs are powered by low-m discs launching sub-relativistic and relativistic jets, respectively. Low-power slow jets and disc/corona winds from moderately high to high-m discs account for the compact and edge-brightened jets of Seyferts, respectively. Jetted H ii galaxies may host weakly active BHs. Fuel-starved BHs and recurrent activity account for ALG properties. In conclusion, specific accretion-ejection states of active BHs determine the radio production and the optical classification of local active galaxies.
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| 4. |
- Dullo, B. T., et al.
(författare)
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LeMMINGs. VI. Connecting nuclear activity to bulge properties of active and inactive galaxies: radio scaling relations and galaxy environment
- 2023
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Ingår i: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 522:3, s. 3412-3438
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Tidskriftsartikel (refereegranskat)abstract
- Multiwavelength studies indicate that nuclear activity and bulge properties are closely related, but the details remain unclear. To study this further, we combine Hubble Space Telescope bulge structural and photometric properties with 1.5 GHz, e-MERLIN nuclear radio continuum data from the LeMMINGs survey for a large sample of 173 'active' galaxies (LINERs and Seyferts) and 'inactive' galaxies (H IIs and absorption line galaxies, ALGs). Dividing our sample into active and inactive, they define distinct (radio core luminosity)-(bulge mass), LR,core − M∗,bulge, relations, with a mass turnover at M∗,bulge ∼ 109.8±0.3M☉ (supermassive blackhole mass MBH ∼ 106.8±0.3M☉), which marks the transition from AGN-dominated nuclear radio emission in more massive bulges to that mainly driven by stellar processes in low-mass bulges. None of our 10/173 bulge-less galaxies host an AGN. The AGN fraction increases with increasing M∗,bulge such that foptical_AGN ∝ M∗,bulge0.24±0.06 and fradio_AGN ∝ M∗,bulge0.24±0.05. Between M∗,bulge ∼ 108.5 and 1011.3M☉, foptical_AGN steadily rises from 15 ± 4 to 80 ± 5 per cent. We find that at fixed bulge mass, the radio loudness, nuclear radio activity, and the (optical and radio) AGN fraction exhibit no dependence on environment. Radio-loud hosts preferentially possess an early-type morphology than radio-quiet hosts, the two types are however indistinguishable in terms of bulge Sérsic index and ellipticity, while results on the bulge inner logarithmic profile slope are inconclusive. We finally discuss the importance of bulge mass in determining the AGN triggering processes, including potential implications for the nuclear radio emission in nearby galaxies.
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| 5. |
- Dullo, B. T., et al.
(författare)
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LeMMINGs: V. Nuclear activity and bulge properties: A detailed multi-component decomposition of e -MERLIN Palomar galaxies with HST
- 2023
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 675
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Tidskriftsartikel (refereegranskat)abstract
- We used high-resolution HST imaging and e-MERLIN 1.5-GHz observations of galaxy cores from the LeMMINGs survey to investigate the relation between optical structural properties and nuclear radio emission for a large sample of galaxies. We performed accurate, multi-component decompositions of new surface brightness profiles extracted from HST images for 163 LeMMINGs galaxies and fitted up to six galaxy components (e.g. bulges, discs, AGN, bars, rings, spiral arms, and nuclear star clusters) simultaneously with Sérsic and/or core-Sérsic models. By adding such decomposition data for ten LeMMINGs galaxies from our past work, the final sample of 173 nearby galaxies (102 Ss, 42 S0s, 23 Es, plus six Irr) with a typical bulge stellar mass of M∗,bulge ~ 106 -1012.5 M⊙ encompasses all optical spectral classes: low-ionisation nuclear emission-line region (LINER), Seyfert, Absorption Line Galaxy (ALG), and H′ ¯II. We show that the bulge mass can be significantly overestimated in many galaxies when components such as bars, rings, and spirals are not included in the fits. We additionally implemented a Monte Carlo method to determine errors on the bulge, disc, and other fitted structural parameters. Moving (in the opposite direction) across the Hubble sequence, that is from the irregular to elliptical galaxies, we confirm that bulges become larger, more prominent, and round. Such bulge dominance is associated with a brighter radio core luminosity. We also find that the radio detection fraction increases with bulge mass. At M∗,bulge ≫ 1011 M⊙, the radio detection fraction is 77%, declining to 24% for M∗,bulge < 1010 M⊙. Furthermore, we observe that core-Sérsic bulges tend to be systematically round and to possess high radio core luminosities and boxy-distorted or pure elliptical isophotes. However, there is no evidence for the previously alleged strong tendency of galaxies'central structures (i.e. a sharp Sérsic, core-Sérsic dichotomy) with their radio loudness, isophote shape, and flattening.
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| 6. |
- Allesøe, Rosa Lundbye, et al.
(författare)
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Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models
- 2023
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Ingår i: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 41:3, s. 399-408
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Tidskriftsartikel (refereegranskat)abstract
- The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate such data and applied it to a cohort of 789 people with newly diagnosed type 2 diabetes with deep multi-omics phenotyping from the DIRECT consortium. Using in silico perturbations, we identified drug–omics associations across the multi-modal datasets for the 20 most prevalent drugs given to people with type 2 diabetes with substantially higher sensitivity than univariate statistical tests. From these, we among others, identified novel associations between metformin and the gut microbiota as well as opposite molecular responses for the two statins, simvastatin and atorvastatin. We used the associations to quantify drug–drug similarities, assess the degree of polypharmacy and conclude that drug effects are distributed across the multi-omics modalities.
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| 7. |
- Mutie, I., et al.
(författare)
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Radio jets in NGC 1068 with e-MERLIN and VLA: Structure and morphology
- 2024
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Ingår i: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 527:4, s. 11756-11765
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Tidskriftsartikel (refereegranskat)abstract
- We present new high-sensitivity e-MERLIN and Very Large Array (VLA) radio images of the prototypical Seyfert 2 galaxy NGC 1068 at 5, 10, and 21 GHz. We image the radio jet, from the compact components north-east (NE), C, S1, and S2 to the faint double-lobed jet structure of the NE and south-west (SW) jet lobes. We map the jet between 15 kλ and 3300 kλ spatial scales by combining enhanced-Multi Element Radio Linked Interferometer Network (e-MERLIN) and VLA data for the first time. Components NE, C, and S2 have steep spectra indicative of optically thin non-Thermal emission domination between 5 and 21 GHz. Component S1, which is where the active galactic nucleus resides, has a flat radio spectrum. We report a new component, S2a, a part of the southern jet. We compare these new data with the MERLIN and VLA data observed in 1983, 1992, and 1995 and report a flux decrease by a factor of 2 in component C, suggesting variability of this jet component. With the high angular resolution e-MERLIN maps, we detect the bow shocks in the NE jet lobe that coincide with the molecular gas outflows observed with ALMA. The NE jet lobe has a jet power of 6.7 × 1042 erg s-1 and is considered to be responsible for driving out the dense molecular gas observed with ALMA around the same region.
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