| 1. |
- Orlando, Ludovic, et al.
(författare)
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Recalibrating Equus evolution using the genome sequence of an early Middle Pleistocene horse
- 2013
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 499:7456, s. 74-
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Tidskriftsartikel (refereegranskat)abstract
- The rich fossil record of equids has made them a model for evolutionary processes(1). Here we present a 1.12-times coverage draft genome from a horse bone recovered from permafrost dated to approximately 560-780 thousand years before present (kyr BP)(2,3). Our data represent the oldest full genome sequence determined so far by almost an order of magnitude. For comparison, we sequenced the genome of a Late Pleistocene horse (43 kyr BP), and modern genomes of five domestic horse breeds (Equus ferus caballus), a Przewalski's horse (E. f. prze-walskii) and a donkey (E. asinus). Our analyses suggest that the Equus lineage giving rise to all contemporary horses, zebras and donkeys originated 4.0-4.5 million years before present (Myr BP), twice the conventionally accepted time to the most recent common ancestor of the genus Equus(4,5). We also find that horse population size fluctuated multiple times over the past 2 Myr, particularly during periods of severe climatic changes. We estimate that the Przewalski's and domestic horse populations diverged 38-72 kyr BP, and find no evidence of recent admixture between the domestic horse breeds and the Przewalski's horse investigated. This supports the contention that Przewalski's horses represent the last surviving wild horse population(6). We find similar levels of genetic variation among Przewalski's and domestic populations, indicating that the former are genetically viable and worthy of conservation efforts. We also find evidence for continuous selection on the immune system and olfaction throughout horse evolution. Finally, we identify 29 genomic regions among horse breeds that deviate from neutrality and show low levels of genetic variation compared to the Przewalski's horse. Such regions could correspond to loci selected early during domestication.
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| 2. |
- Rasmussen, Morten, et al.
(författare)
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Ancient human genome sequence of an extinct Palaeo-Eskimo
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 463:7282, s. 757-762
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Tidskriftsartikel (refereegranskat)abstract
- We report here the genome sequence of an ancient human. Obtained from ∼4,000-year-old permafrost-preserved hair, the genome represents a male individual from the first known culture to settle in Greenland. Sequenced to an average depth of 20×, we recover 79% of the diploid genome, an amount close to the practical limit of current sequencing technologies. We identify 353,151 high-confidence single-nucleotide polymorphisms (SNPs), of which 6.8% have not been reported previously. We estimate raw read contamination to be no higher than 0.8%. We use functional SNP assessment to assign possible phenotypic characteristics of the individual that belonged to a culture whose location has yielded only trace human remains. We compare the high-confidence SNPs to those of contemporary populations to find the populations most closely related to the individual. This provides evidence for a migration from Siberia into the New World some 5,500 years ago, independent of that giving rise to the modern Native Americans and Inuit.
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| 3. |
- 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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| 4. |
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| 5. |
- Andersson, Anders-Petter, 1969-
(författare)
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Interaktiv musikkomposition
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation, titled Interactive Music Composition, is a practice based Ph.D. thesis in the field of Musicology. The purpose is to explore if and how one can compose computer based interactive music, that is musically satisfying for an interacting audience, consisting of both laymen and skilled musicians. The text describes the design and reflection in two interactive music installations: Do-Be-DJ, open-air installation in a public park, and, Mufi, with modular and moveable interface. Based on methods and perspectives in Musicology and Interaction Design, a composition model for interactive music is developed. The model investigates the experience dimensions listen, explore, compose and collaborate. It also investigates the design dimensions of interaction, narrative structure, composition rule and sound node. The conceptual approach is to apply improvisation and composition methods from jazz, pop and groove based music on interactive music. It also uses the concepts of openess in musical structures and interpretation, musical mediation of actions and meaning and everyday use of music, when composing interactive music. The dissertation contributes to an understanding of how to create composition techniques for interactive music, such as: Direct, varied and shifting response. It reflects on the change in meaning of the musicological terms composition, improvisation, musical work, listener, musician and audience. And on the interaction design terms interaction, gameplay, system and user. The term co-creator is used to describe an actively, interacting and collaborating person, to complement traditional terms like audience, performer and user.
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| 6. |
- Andersson, Robin, 1980-
(författare)
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Decoding the Structural Layer of Transcriptional Regulation : Computational Analyses of Chromatin and Chromosomal Aberrations
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Gene activity is regulated at two separate layers. Through structural and chemical properties of DNA – the primary layer of encoding – local signatures may enable, or disable, the binding of proteins or complexes of them with regulatory potential to the DNA. At a higher level – the structural layer of encoding – gene activity is regulated through the properties of higher order DNA structure, chromatin, and chromosome organization. Cells with abnormal chromosome compaction or organization, e.g. cancer cells, may thus have perturbed regulatory activities resulting in abnormal gene activity. Hence, there is a great need to decode the transcriptional regulation encoded in both layers to further our understanding of the factors that control activity and life of a cell and, ultimately, an organism. Modern genome-wide studies with those aims rely on data-intense experiments requiring sophisticated computational and statistical methods for data handling and analyses. This thesis describes recent advances of analyzing experimental data from quantitative biological studies to decipher the structural layer of encoding in human cells. Adopting an integrative approach when possible, combining multiple sources of data, allowed us to study the influences of chromatin (Papers I and II) and chromosomal aberrations (Paper IV) on transcription. Combining chromatin data with chromosomal aberration data allowed us to identify putative driver oncogenes and tumor-suppressor genes in cancer (Paper IV). Bayesian approaches enabling the incorporation of background information in the models and the adaptability of such models to data have been very useful. Their usages yielded accurate and narrow detection of chromosomal breakpoints in cancer (Papers III and IV) and reliable positioning of nucleosomes and their dynamics during transcriptional regulation at functionally relevant regulatory elements (Paper II). Using massively parallel sequencing data, we explored the chromatin landscapes of human cells (Papers I and II) and concluded that there is a preferential and evolutionary conserved positioning at internal exons nearly unaffected by the transcriptional level. We also observed a strong association between certain histone modifications and the inclusion or exclusion of an exon in the mature gene transcript, suggesting a functional role in splicing.
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| 7. |
- Cordova, R., et al.
(författare)
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Dietary intake of advanced glycation end products (AGEs) and changes in body weight in European adults
- 2020
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Ingår i: European Journal of Nutrition. - : Springer Berlin/Heidelberg. - 1436-6207 .- 1436-6215. ; 59, s. 2893-2904
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Advanced glycation end products (AGEs) can be formed in foods by the reaction of reducing sugars with proteins, and have been shown to induce insulin resistance and obesity in experimental studies. We examined the association between dietary AGEs intake and changes in body weight in adults over an average of 5 years of follow-up.Methods: A total of 255,170 participants aged 25–70 years were recruited in ten European countries (1992–2000) in the PANACEA study (Physical Activity, Nutrition, Alcohol, Cessation of smoking, Eating out of home in relation to Anthropometry), a sub-cohort of the EPIC (European Prospective Investigation into Cancer and Nutrition). Body weight was measured at recruitment and self-reported between 2 and 11 years later depending on the study center. A reference database for AGEs was used containing UPLC–MS/MS-measured Nε-(carboxymethyl)-lysine (CML), Nε-(1-carboxyethyl)-lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) in 200 common European foods. This reference database was matched to foods and decomposed recipes obtained from country-specific validated dietary questionnaires in EPIC and intake levels of CEL, CML, and MG-H1 were estimated. Associations between dietary AGEs intake and body weight change were estimated separately for each of the three AGEs using multilevel mixed linear regression models with center as random effect and dietary AGEs intake and relevant confounders as fixed effects.Results: A one-SD increment in CEL intake was associated with 0.111 kg (95% CI 0.087–0.135) additional weight gain over 5 years. The corresponding additional weight gain for CML and MG-H1 was 0.065 kg (0.041–0.089) and 0.034 kg (0.012, 0.057), respectively. The top six food groups contributing to AGEs intake, with varying proportions across the AGEs, were cereals/cereal products, meat/processed meat, cakes/biscuits, dairy, sugar and confectionary, and fish/shellfish.Conclusion: In this study of European adults, higher intakes of AGEs were associated with marginally greater weight gain over an average of 5 years of follow-up.
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| 8. |
- Davies, Siwan M, et al.
(författare)
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Identification of the Fugloyarbanki tephra in the NGRIP ice-core: a key tie-point for marine and ice-core sequences during the last glacial period
- 2008
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Ingår i: Journal of Quaternary Science. - : Wiley. - 0267-8179 .- 1099-1417. ; 23:5, s. 409-414
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Tidskriftsartikel (refereegranskat)abstract
- A visible tephra horizon in the NGRIP ice core has been identified by geochemical analysis as the Fugloyarbanki Tephra, a widespread marker horizon in marine cores from the Faroe Islands area and the northern North Atlantic. An age of 26 740 ± 390 yr b2k (1σ uncertainty) is derived for this tephra according to the new Greenland Ice Core Chronology (GICC05) based on multi-parameter counting of annual layers. Detection of this tephra for the first time within the NGRIP ice core provides a key tie-point between marine and ice-core records during the transition between MIS 3 and 2. Identification of this volcanic event within the Greenland records demonstrates the future potential of using tephrochronology to precisely correlate palaeoarchives in widely separated localities that span the last glacial period, as well as providing a potential method for examining the extent of the radiocarbon marine reservoir effect at this time.
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| 9. |
- Hougaard, Jesper Leth, et al.
(författare)
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The nerve fibre layer symmetry test: computerized evaluation of human retinal nerve fibre layer thickness as measured by optical coherence tomography
- 2004
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Ingår i: Acta Ophthalmologica Scandinavica. - : Wiley. - 1395-3907 .- 1600-0420. ; 82:4, s. 410-418
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To present and test a new interpretative concept, the nerve fibre layer symmetry test (NST), for computerized evaluation of retinal nerve fibre layer thickness (RNFLT) as measured by optical coherence tomography (OCT) in glaucoma. Methods: The NST concept was constructed and tested in a pilot study. A total of 32 healthy and 40 age-matched glaucomatous eyes were included and examined by OCT, computerized perimetry, RNFL/disc photography, tonometry and a general ophthalmologic examination. Results: The observed NST sensitivity and specificity were high, at 38/40 eyes (95%) and 32/32 eyes (100%), respectively, and 40/40 eyes (100%), and 31/32 eyes (97%), respectively, when correcting the OCT RNFLT measurement for the influence of variability in image signal/quality. The NST sensitivity was 8-10% higher than the single most sensitive traditional OCT RNFLT parameter; this difference was not statistically significant in this small sample. Conclusion: The NST showed high specificity and sensitivity for detection of RNFLT attenuation indicating early to severe glaucoma. Although promising, the NST needs to be further developed and validated in larger study samples and in patients with various stages of glaucomatous damage.
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| 10. |
- Häfner, Sophia J., et al.
(författare)
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Ribosomal RNA 2′-O-methylation dynamics impact cell fate decisions
- 2023
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Ingår i: Developmental Cell. - 1534-5807. ; 58:17, s. 9-1609
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Tidskriftsartikel (refereegranskat)abstract
- Translational regulation impacts both pluripotency maintenance and cell differentiation. To what degree the ribosome exerts control over this process remains unanswered. Accumulating evidence has demonstrated heterogeneity in ribosome composition in various organisms. 2′-O-methylation (2′-O-me) of rRNA represents an important source of heterogeneity, where site-specific alteration of methylation levels can modulate translation. Here, we examine changes in rRNA 2′-O-me during mouse brain development and tri-lineage differentiation of human embryonic stem cells (hESCs). We find distinct alterations between brain regions, as well as clear dynamics during cortex development and germ layer differentiation. We identify a methylation site impacting neuronal differentiation. Modulation of its methylation levels affects ribosome association of the fragile X mental retardation protein (FMRP) and is accompanied by an altered translation of WNT pathway-related mRNAs. Together, these data identify ribosome heterogeneity through rRNA 2′-O-me during early development and differentiation and suggest a direct role for ribosomes in regulating translation during cell fate acquisition.
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