| 1. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 2. |
- Wiedorn, Max O., et al.
(författare)
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Megahertz serial crystallography
- 2018
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The new European X-ray Free-Electron Laser is the first X-ray free-electron laser capable of delivering X-ray pulses with a megahertz inter-pulse spacing, more than four orders of magnitude higher than previously possible. However, to date, it has been unclear whether it would indeed be possible to measure high-quality diffraction data at megahertz pulse repetition rates. Here, we show that high-quality structures can indeed be obtained using currently available operating conditions at the European XFEL. We present two complete data sets, one from the well-known model system lysozyme and the other from a so far unknown complex of a beta-lactamase from K. pneumoniae involved in antibiotic resistance. This result opens up megahertz serial femtosecond crystallography (SFX) as a tool for reliable structure determination, substrate screening and the efficient measurement of the evolution and dynamics of molecular structures using megahertz repetition rate pulses available at this new class of X-ray laser source.
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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. |
- Chen, Mo, et al.
(författare)
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Molecular Dynamics Simulations of the Ionic Liquid 1-n-Butyl-3-Methylimidazolium Chloride and Its Binary Mixtures with Ethanol
- 2014
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Ingår i: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 10:10, s. 4465-4479
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Tidskriftsartikel (refereegranskat)abstract
- Room temperature ionic liquids (ILs) of the imidazolium family have attracted much attention during the past decade for their capability to dissolve biomass. Besides experimental work, numerous compuational studies have been concerned with the physical properties of both neat ILs and their interactions with different solutes, in particular, carbohydrates. Many classical force fields designed specifically for ILs have been found to yield viscosities that are too high for the liquid state, which has been attributed to the fact that the effective charge densities are too high due to the lack of electronic polarizability. One solution to this problem has been uniform scaling of the partial charges by a scale factor in the range 0.6-0.9, depending on model. This procedure has been shown to improve the viscosity of the models, and also to positively affect other properties, such as diffusion constants and ionic conductivity. However, less attention has been paid to how this affects the overall thermodynamics of the system, and the problems it might create when the IL models are combined with other force fields (e.g., for solutes). In the present work, we employ three widely used IL force fields to simulate 1-n-buty1-3-methyl-imidazolium chloride in both the crystal and the liquid state, as well as its binary mixture with ethanol. Two approaches are used: one in which the ionic charge is retained at its full integer value and one in which the partial charges are uniformly reduced to 85%. We investigate and calculate crystal and liquid structures, molar heat capacities, heats of fusion, self-diffusion constants, ionic conductivity, and viscosity for the neat IL, and ethanol activity as a function of ethanol concentration for the binary mixture. We show that properties of the crystal are less affected by charge scaling compared to the liquid. In the liquid state, transport properties of the neat IL are generally improved by scaling, whereas values for the heat of fusion are unaffected, and results for the heat capacity are ambiguous. Neither full nor reduced charges could reproduce experimental ethanol activities for the whole range of compositions.
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| 6. |
- de Rezende, Susanna F., 1989-, et al.
(författare)
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Lifting with Simple Gadgets and Applications to Circuit and Proof Complexity
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We significantly strengthen and generalize the theorem lifting Nullstellensatz degree to monotone span program size by Pitassi and Robere (2018) so that it works for any gadget with high enough rank, in particular, for useful gadgets such as equality and greater-than. We apply our generalized theorem to solve two open problems:We present the first result that demonstrates a separation in proof power for cutting planes with unbounded versus polynomially bounded coefficients. Specifically, we exhibit CNF formulas that can be refuted in quadratic length and constant line space in cutting planes with unbounded coefficients, but for which there are no refutations in subexponential length and subpolynomialline space if coefficients are restricted to be of polynomial magnitude.We give the first explicit separation between monotone Boolean formulas and monotone real formulas. Specifically, we give an explicit family of functions that can be computed with monotone real formulas of nearly linear size but require monotone Boolean formulas of exponential size. Previously only a non-explicit separation was known.An important technical ingredient, which may be of independent interest, is that we show that the Nullstellensatz degree of refuting the pebbling formula over a DAG G over any field coincides exactly with the reversible pebbling price of G. In particular, this implies that the standard decision tree complexity and the parity decision tree complexity of the corresponding falsified clause search problem are equal.
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| 7. |
- de Rezende, Susanna F., et al.
(författare)
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Nullstellensatz Size-Degree Trade-offs from Reversible Pebbling
- 2019
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Ingår i: Proceedings of the 34th Annual Computational Complexity Conference (CCC ’19). - : Schloss Dagstuhl- Leibniz-Zentrum fur Informatik GmbH, Dagstuhl Publishing. - 9783959771160 ; , s. 18:1-18:16
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Konferensbidrag (refereegranskat)abstract
- We establish an exactly tight relation between reversible pebblings of graphs and Nullstellensatz refutations of pebbling formulas, showing that a graph G can be reversibly pebbled in time t and space s if an only if there is a Nullstellensatz refutation of the pebbling formula over G in size t + 1 and degree s (independently of the field in which the Nullstellensatz refutation is made). We use this correspondence to prove a number of strong size-degree trade-offs for Nullstellensatz, which to the best of our knowledge are the first such results for this proof system.
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| 8. |
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| 9. |
- Rossitto, Chiara, et al.
(författare)
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Data-Enabled Sustainability : The Collective Work of Turning Data into Actions for Environmental Care
- 2023
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Ingår i: CSCW '23 Companion. - : Association for Computing Machinery. - 9798400701290 ; , s. 506-511
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Konferensbidrag (refereegranskat)abstract
- This one-day workshop invites discussions on the role of data and data-enabled practices in addressing challenges of environmental sustainability. Fostering acts of care for the environment is a complex endeavor entailing multi-lifespan relations to people and institutions, to the environment and other non-human actors, and to existing infrastructures and processes. The workshop addresses such challenges by exploring the role of data, and the work of making them actionable for the many actors involved in protecting the environment. It will bring together interdisciplinary scholars, representatives of public institutions, activists, environmental collectives, and IT practitioners interested in the design of more sustainable futures. The workshop will discuss analytical and design issues of data-enabled sustainability, along with the practical opportunities of using data to infrastructure acts of care for the environment. The workshop will accommodate up to twenty participants and will be mainly run on-site.
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| 10. |
- Rossitto, Chiara, et al.
(författare)
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Towards Digital Environmental Stewardship : the Work of Caring for the Environment in Waste Management
- 2022
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Ingår i: Conference on Human Factors in Computing Systems - Proceedings. - New York, NY, USA : Association for Computing Machinery. - 9781450391573 ; , s. 1-16
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Konferensbidrag (refereegranskat)abstract
- This paper discusses Digital Environmental Stewardship as an analytical framework that can help HCI scholarship to understand, design, and assess sociotechnical interventions concerned with sustainable waste management practices. Drawing on environmental studies, we outline key concepts of environmental stewardship - namely actors, capacity, and motivations - to unpack how different initiatives for handling waste are organised, both through grassroots and top-down interventions, and through varying sociotechnical configurations. We use these dimensions to analyse three different cases of waste management that illustrate how actions of care for the environment are ecologically organised, and what challenges might hinder them beyond -or besides- behavioural motivations. We conclude with a discussion on the orientation to action that the suggested framework provides, and its role in understanding, designing and assessing digital technologies in this domain. We argue that examining how stewardship actions fold into each other helps design sociotechnical interventions for managing waste from within a relational perspective.
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