| 1. |
- 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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| 2. |
- Baum, Sebastian, et al.
(författare)
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Dark matter capture, subdominant WIMPs, and neutrino observatories
- 2017
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Ingår i: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 95:4
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Tidskriftsartikel (refereegranskat)abstract
- Weakly interacting massive particles (WIMPs), which are among the best motivated dark matter (DM) candidates, could make up all or only a fraction of the total DM budget. We consider a scenario in which WIMPs are a subdominant DM component; such a scenario would affect both current direct and indirect bounds on the WIMP-nucleon scattering cross section. In this paper we focus on indirect searches for the neutrino flux produced by annihilation of subdominant WIMPs captured by the Sun or the Earth via either spin-dependent or spin-independent scattering. We derive the annihilation rate and the expected neutrino flux at neutrino observatories. In our computation, we include an updated chemical composition of the Earth with respect to the previous literature, leading to an increase of the Earth's capture rate for spin-dependent scattering by a factor of 3. Results are compared with current bounds from Super-Kamiokande and IceCube. We discuss the scaling of bounds from both direct and indirect detection methods with the WIMP abundance.
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| 3. |
- Baum, Sebastian, et al.
(författare)
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Hunting for scalar lepton partners at future electron colliders
- 2020
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Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 102:1
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Tidskriftsartikel (refereegranskat)abstract
- New physics close to the electroweak scale is well motivated by a number of theoretical arguments. However, colliders, most notably the Large Hadron Collider, have failed to deliver evidence for physics beyond the Standard Model. One possibility for how new electroweak-scale particles could have evaded detection so far is if they carry only electroweak charge, i.e., are color neutral. Future e(+)e(-) colliders are prime tools to study such new physics. Here, we investigate the sensitivity of e(+)e(-) colliders to scalar partners of the charged leptons, known as sleptons in supersymmetric extensions of the Standard Model. In order to allow such scalar lepton partners to decay, we consider models with an additional neutral fermion, which in supersymmetric models corresponds to a neutralino. We demonstrate that future e(+)e(-) colliders would be able to probe most of the kinematically accessible parameter space, i.e., where the mass of the scalar lepton partner is less than half of the collider's center-of-mass energy, with only a few days of data. Besides constraining more general models, this would allow to probe some well motivated dark matter scenarios in the Minimal Supersymmetric Standard Model, in particular the incredible bulk and stau coannihilation scenarios.
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| 4. |
- Baum, Sebastian, et al.
(författare)
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Paleodetectors for Galactic supernova neutrinos
- 2020
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Ingår i: Physical Review D. - : American Physical Society (APS). - 2470-0010 .- 2470-0029. ; 101:10
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Tidskriftsartikel (refereegranskat)abstract
- Paleodetectors are a proposed experimental technique in which one would search for traces of recoiling nuclei in ancient minerals. Natural minerals on Earth are as old as O(1) Gyr and, in many minerals, the damage tracks left by recoiling nuclei are also preserved for timescales long compared to 1 Gyr once created. Thus, even reading out relatively small target samples of order 100 g, paleodetectors would allow one to search for very rare events thanks to the large exposure, epsilon similar to 100 g Gyr = 10(5) t yr. Here, we explore the potential of paleodetectors to measure nuclear recoils induced by neutrinos from Galactic core collapse supernovae. We find that they would not only allow for a direct measurement of the average core collapse supernova rate in the Milky Way, but would also contain information about the time dependence of the local supernova rate over the past similar to 1 Gyr. Since the supernova rate is thought to be directly proportional to the star formation rate, such a measurement would provide a determination of the local star formation history. We investigate the sensitivity of paleodetectors to both a smooth time evolution and an enhancement of the core collapse supernova rate on relatively short timescales, as would be expected for a starburst period in the local group.
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| 5. |
- Baum, Sebastian, et al.
(författare)
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Searching for dark matter with paleo-detectors
- 2020
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Ingår i: Physics Letters B. - : ELSEVIER. - 0370-2693 .- 1873-2445. ; 803
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Tidskriftsartikel (refereegranskat)abstract
- A large experimental program is underway to extend the sensitivity of direct detection experiments, searching for interaction of Dark Matter with nuclei, down to the neutrino floor. However, such experiments are becoming increasingly difficult and costly due to the large target masses and exquisite background rejection needed for the necessary improvements in sensitivity. We investigate an alternative approach to the detection of Dark Matter-nucleon interactions: Searching for the persistent traces left by Dark Matter scattering in ancient minerals obtained from much deeper than current underground laboratories. We estimate the sensitivity of paleo-detectors, which extends far beyond current upper limits for a wide range of Dark Matter masses. The sensitivity of our proposal also far exceeds the upper limits set by Snowden-Ifft et al. more than three decades ago using ancient Mica in an approach similar to paleo-detectors.
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| 6. |
- Baum, Sebastian, et al.
(författare)
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Searching for Dark Matter with Paleo-Detectors
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- A large experimental program is underway to extend the sensitivity of direct detection experiments, searching for interactions of Dark Matter with nuclei, down to the neutrino floor. However, such experiments are becoming increasingly difficult and costly due to the large target masses and exquisite background rejection needed for the necessary improvements in sensitivity. We investigate an alternative approach to the detection of Dark Matter--nucleon interactions: Searching for the persistent traces left by Dark Matter scattering in ancient minerals obtained from much deeper than current underground laboratories. We estimate the sensitivity of paleo-detectors, which extends far beyond current upper limits for a wide range of Dark Matter masses.
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| 7. |
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| 8. |
- Drukier, Andrzej K., et al.
(författare)
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Paleo-detectors : Searching for Dark Matter with Ancient Minerals
- 2019
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Ingår i: Physical Review D. Particles and fields. - : AMER PHYSICAL SOC. - 0556-2821 .- 1089-4918. ; 99:4
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Tidskriftsartikel (refereegranskat)abstract
- We explore paleo-detectors as an approach to the direct detection of weakly interacting massive particle (WIMP) dark matter radically different from conventional detectors. Instead of instrumenting a (large) target mass in a laboratory in order to observe WIMP-induced nuclear recoils in real time, the approach is to examine ancient minerals for traces of WIMP-nucleus interactions recorded over timescales as large as 1 Gyr. Here, we discuss the paleo-detector proposal in detail, including background sources and possible target materials. In order to suppress backgrounds induced by radioactive contaminants such as uranium, we propose to use minerals found in marine evaporites or in ultrabasic rocks. We estimate the sensitivity of paleo-detectors to spin-independent and spin-dependent WIMP-nucleus interactions. The sensitivity to low-mass WIMPs with masses mχ≲10 GeV extends to WIMP-nucleon cross sections many orders of magnitude smaller than current upper limits. For heavier WIMPs with masses mχ≳30 GeV cross sections a factor of a few to ∼100 smaller than current upper limits can be probed by paleo-detectors.
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| 9. |
- Edwards, Thomas D. P., et al.
(författare)
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Digging for dark matter : Spectral analysis and discovery potential of paleo-detectors
- 2019
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Ingår i: Physical Review D. Particles and fields. - : AMER PHYSICAL SOC. - 0556-2821 .- 1089-4918. ; 99:4
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Tidskriftsartikel (refereegranskat)abstract
- Paleo-detectors are a recently proposed method for the direct detection of dark matter (DM). In such detectors, one would search for the persistent damage features left by DM–nucleus interactions in ancient minerals. Initial sensitivity projections have shown that paleo-detectors could probe much of the remaining weakly interacting massive particle (WIMP) parameter space. In this paper, we improve upon the cut-and-count approach previously used to estimate the sensitivity by performing a full spectral analysis of the background- and DM-induced signal spectra. We consider two scenarios for the systematic errors on the background spectra: (i) systematic errors on the normalization only, and (ii) systematic errors on the shape of the backgrounds. We find that the projected sensitivity is rather robust to imperfect knowledge of the backgrounds. Finally, we study how well the parameters of the true WIMP model could be reconstructed in the hypothetical case of a WIMP discovery.
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| 10. |
- Jordan, Johnathon R., et al.
(författare)
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Measuring Changes in the Atmospheric Neutrino Rate over Gigayear Timescales
- 2020
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 125:23
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Tidskriftsartikel (refereegranskat)abstract
- Measuring the cosmic ray flux over timescales comparable to the age of the Solar System, similar to 4.5 Gyr, could provide a new window on the history of the Earth, the Solar System, and even our Galaxy. We present a technique to indirectly measure the rate of cosmic rays as a function of time using the imprints of atmospheric neutrinos in paleo-detectors, natural minerals that record damage tracks from nuclear recoils. Minerals commonly found on Earth are less than or similar to 1 Gyr old, providing the ability to look back across cosmic ray history on timescales of the same order as the age of the Solar System. Given a collection of differently aged samples dated with reasonable accuracy, this technique is particularly well-suited to measuring historical changes in the cosmic ray flux at Earth and is broadly applicable in astrophysics and geophysics.
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