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- Noguchi, S, et al.
(author)
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FANTOM5 CAGE profiles of human and mouse samples
- 2017
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In: Scientific data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4, s. 170112-
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Journal article (peer-reviewed)abstract
- In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands of samples, consisting of a variety of primary cells, tissues, cell lines, and time series samples during cell activation and development, were subjected to a uniform pipeline of CAGE data production. The analysis pipeline started by measuring RNA extracts to assess their quality, and continued to CAGE library production by using a robotic or a manual workflow, single molecule sequencing, and computational processing to generate frequencies of transcription initiation. Resulting data represents the consequence of transcriptional regulation in each analyzed state of mammalian cells. Non-overlapping peaks over the CAGE profiles, approximately 200,000 and 150,000 peaks for the human and mouse genomes, were identified and annotated to provide precise location of known promoters as well as novel ones, and to quantify their activities.
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- Carmona-Gutierrez, D., et al.
(author)
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Guidelines and recommendations on yeast cell death nomenclature
- 2018
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In: Microbial Cell. - : Shared Science Publishers OG. - 2311-2638. ; 5:1, s. 4-31
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Research review (peer-reviewed)abstract
- Elucidating the biology of yeast in its full complexity has major implications for science, medicine and industry. One of the most critical processes determining yeast life and physiology is cellular demise. However, the investigation of yeast cell death is a relatively young field, and a widely accepted set of concepts and terms is still missing. Here, we propose unified criteria for the definition of accidental, regulated, and programmed forms of cell death in yeast based on a series of morphological and biochemical criteria. Specifically, we provide consensus guidelines on the differential definition of terms including apoptosis, regulated necrosis, and autophagic cell death, as we refer to additional cell death routines that are relevant for the biology of (at least some species of) yeast. As this area of investigation advances rapidly, changes and extensions to this set of recommendations will be implemented in the years to come. Nonetheless, we strongly encourage the authors, reviewers and editors of scientific articles to adopt these collective standards in order to establish an accurate framework for yeast cell death research and, ultimately, to accelerate the progress of this vibrant field of research.
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- Ramilowski, JA, et al.
(author)
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Functional annotation of human long noncoding RNAs via molecular phenotyping
- 2020
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In: Genome research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 30:7, s. 1060-1072
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Journal article (peer-reviewed)abstract
- Long noncoding RNAs (lncRNAs) constitute the majority of transcripts in the mammalian genomes, and yet, their functions remain largely unknown. As part of the FANTOM6 project, we systematically knocked down the expression of 285 lncRNAs in human dermal fibroblasts and quantified cellular growth, morphological changes, and transcriptomic responses using Capped Analysis of Gene Expression (CAGE). Antisense oligonucleotides targeting the same lncRNAs exhibited global concordance, and the molecular phenotype, measured by CAGE, recapitulated the observed cellular phenotypes while providing additional insights on the affected genes and pathways. Here, we disseminate the largest-to-date lncRNA knockdown data set with molecular phenotyping (over 1000 CAGE deep-sequencing libraries) for further exploration and highlight functional roles for ZNF213-AS1 and lnc-KHDC3L-2.
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- Filippatos, G. S., et al.
(author)
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Independent academic Data Monitoring Committees for clinical trials in cardiovascular and cardiometabolic diseases
- 2017
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In: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 19:4, s. 449-456
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Journal article (peer-reviewed)abstract
- Data Monitoring Committees (DMCs) play a crucial role in the conducting of clinical trials to ensure the safety of study participants and to maintain a trial's scientific integrity. Generally accepted standards exist for DMC composition and operational conduct. However, some relevant issues are not specifically addressed in current guidance documents, resulting in uncertainties regarding optimal approaches for communication between the DMC, steering committee, and sponsors, release of information, and liability protection for DMC members. The Heart Failure Association (HFA) of the European Society of Cardiology (ESC), in collaboration with the Clinical Trials Unit of the European Heart Agency (EHA) of the ESC convened a meeting of international experts in DMCs for cardiovascular and cardiometabolic clinical trials to identify specific issues and develop steps to resolve challenges faced by DMCs.The main recommendations from the meeting relate to methodological consistency, independence, managing conflicts of interest, liability protection, and training of future DMC members. This paper summarizes the key outcomes from this expert meeting, and describes the core set of activities that might be further developed and ultimately implemented by the ESC, HFA, and other interested ESC constituent bodies. The HFA will continue to work with stakeholders in cardiovascular and cardiometabolic clinical research to promote these goals.
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- Fonslet, J., et al.
(author)
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135La as an Auger-electron emitter for targeted internal radiotherapy
- 2018
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In: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 63:1
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Journal article (peer-reviewed)abstract
- 135La has favorable nuclear and chemical properties for Auger-based targeted internal radiotherapy. Here we present detailed investigations of the production, emissions, and dosimetry related to 135La therapy. 135La was produced by 16.5 MeV proton irradiation of metallic natBa on a medical cyclotron, and was isolated and purified by trap-and-release on weak cation-exchange resin. The average production rate was 407 19 MBq A-1 (saturation activity), and the radionuclidic purity was 98% at 20 h post irradiation. Chemical separation recovered > 98 % of the 135La with an effective molar activity of 70 20 GBq mol-1. To better assess cellular and organ dosimetry of this nuclide, we have calculated the x-ray and Auger emission spectra using a Monte Carlo model accounting for effects of multiple vacancies during the Auger cascade. The generated Auger spectrum was used to calculate cellular S-factors. 135La was produced with high specific activity, reactivity, radionuclidic purity, and yield. The emission spectrum and the dosimetry are favorable for internal radionuclide therapy.
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- Hillier, Ladeana W, et al.
(author)
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Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution
- 2004
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In: Nature. - 0028-0836 .- 1476-4687. ; 432:7018, s. 695-716
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Journal article (peer-reviewed)abstract
- We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken is a modern descendant of the dinosaurs and the first non-mammalian amniote to have its genome sequenced, the draft sequence of its genome--composed of approximately one billion base pairs of sequence and an estimated 20,000-23,000 genes--provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes. For example, the evolutionary distance between chicken and human provides high specificity in detecting functional elements, both non-coding and coding. Notably, many conserved non-coding sequences are far from genes and cannot be assigned to defined functional classes. In coding regions the evolutionary dynamics of protein domains and orthologous groups illustrate processes that distinguish the lineages leading to birds and mammals. The distinctive properties of avian microchromosomes, together with the inferred patterns of conserved synteny, provide additional insights into vertebrate chromosome architecture.
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- Lizio, M, et al.
(author)
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Monitoring transcription initiation activities in rat and dog
- 2017
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In: Scientific data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4, s. 170173-
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Journal article (peer-reviewed)abstract
- The promoter landscape of several non-human model organisms is far from complete. As a part of FANTOM5 data collection, we generated 13 profiles of transcription initiation activities in dog and rat aortic smooth muscle cells, mesenchymal stem cells and hepatocytes by employing CAGE (Cap Analysis of Gene Expression) technology combined with single molecule sequencing. Our analyses show that the CAGE profiles recapitulate known transcription start sites (TSSs) consistently, in addition to uncover novel TSSs. Our dataset can be thus used with high confidence to support gene annotation in dog and rat species. We identified 28,497 and 23,147 CAGE peaks, or promoter regions, for rat and dog respectively, and associated them to known genes. This approach could be seen as a standard method for improvement of existing gene models, as well as discovery of novel genes. Given that the FANTOM5 data collection includes dog and rat matched cell types in human and mouse as well, this data would also be useful for cross-species studies.
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- Grapotte, M, et al.
(author)
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Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network
- 2021
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 3297-
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Journal article (peer-reviewed)abstract
- Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism.
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- Hallgren, Mikael, et al.
(author)
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The tubed mega frame - An innovative structural system for tall buildings
- 2015
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In: Concrete - Innovation and Design. - : Technical University of Denmark. ; , s. 473-474, s. 473-474
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Conference paper (peer-reviewed)abstract
- The Tubed Mega Frame is a new structure concept for high-rise buildings which is developed by Tyréns in Sweden. The Tubed Mega Frame consists of large hollow vertical shafts, mega columns, and perimeter walls. In a series of in-depth structural studies, the global response of the system as well as the detailed design of the mega columns and the perimeter walls have been investigated. The studies have been performed on an 800 m high prototype building. Parallel to these studies, the feasibility of the construction process has been the objective in another investigation. The chosen structural material for the Tubed Mega Frame is reinforced high-strength concrete. The conclusions from the studies show that the Tubed Mega Frame is a potentially feasible structural system with high-efficiency for high-rise buildings.
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- Talyzin, Alexandr, et al.
(author)
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Delamination of graphite oxide in a liquid upon cooling
- 2015
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In: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 7:29, s. 12625-12630
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Journal article (peer-reviewed)abstract
- Graphite oxide (GO) in liquid acetonitrile undergoes a transition from an ordered phase around ambient temperature to a gel-like disordered phase at temperatures below 260 K, as demonstrated by in situ X-ray diffraction. The stacking order of GO layers is restored below the freezing point of acetonitrile (199 K). The reversible swelling transition between a stacked crystalline phase and an amorphous delaminated state observed upon cooling provides an unusual example of increased structural disorder at lower temperatures. The formation of the gel-like phase is attributed to the thermo-responsive conformational change of individual GO flakes induced by stronger solvation. Scanning force microscopy demonstrates that GO flakes deposited onto a solid substrate from acetonitrile dispersions at a temperature below 260 K exhibit corrugations and wrinkling which are not observed for the flakes deposited at ambient temperature. The thermo-responsive transition between the delaminated and stacked phases reported here can be used for sonication-free dispersion of graphene oxide, micro-container applications, or the preparation of new composite materials.
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- Tromp, J., et al.
(author)
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World Heart Federation Roadmap for Digital Health in Cardiology
- 2022
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In: GLOBAL HEALTH. - : UBIQUITY PRESS LTD. - 2211-8160 .- 2308-4553 .- 2211-8179. ; 17:1
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Journal article (peer-reviewed)abstract
- More than 500 million people worldwide live with cardiovascular disease (CVD). Health systems today face fundamental challenges in delivering optimal care due to ageing populations, healthcare workforce constraints, financing, availability and affordability of CVD medicine, and service delivery. Digital health technologies can help address these challenges. They may be a tool to reach Sustainable Development Goal 3.4 and reduce premature mortality from non-communicable diseases (NCDs) by a third by 2030. Yet, a range of fundamental barriers prevents implementation and access to such technologies. Health system governance, health provider, patient and technological factors can prevent or distort their implementation. World Heart Federation (WHF) roadmaps aim to identify essential roadblocks on the pathway to effective prevention, detection, and treatment of CVD. Further, they aim to provide actionable solutions and implementation frameworks for local adaptation. This WHF Roadmap for digital health in cardiology identifies barriers to implementing digital health technologies for CVD and provides recommendations for overcoming them.
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- Yu, Hui, et al.
(author)
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Accelerometer sampling requirements for animal behaviour classification and estimation of energy expenditure
- 2023
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In: Animal Biotelemetry. - 2050-3385. ; 11:1
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Journal article (peer-reviewed)abstract
- Background: Biologgers have contributed greatly to studies of animal movement, behaviours and physiology. Accelerometers, among the various on-board sensors of biologgers, have mainly been used for animal behaviour classification and energy expenditure estimation. However, a general principle for the combined sampling duration and frequency for different taxa is lacking. In this study, we evaluated whether Nyquist–Shannon sampling theorem applies to accelerometer-based classification of animal behaviour and energy expenditure approximation. To evaluate the influence of accelerometer sampling frequency on behaviour classification, we annotated accelerometer data from seven European pied flycatchers (Ficedula hypoleuca) freely moving in aviaries. We also used simulated data to systematically evaluate the combined effect of sampling duration and sampling frequency on the performance of estimating signal frequency and amplitude. Results: We found that a sampling frequency higher than Nyquist frequency at 100 Hz was needed to classify fast, short-burst behavioural movements of pied flycatcher, such as swallowing food with a mean frequency of 28 Hz. In contrast, high frequency movements with longer durations such as flight could be characterized adequately using much lower sampling frequency of 12.5 Hz. To identify rapid transient prey catching manoeuvres within these flight bouts, again a high frequency sampling at 100 Hz was needed. For both the experimental data of the flycatchers and the simulated data, the combination of sampling frequency and sampling duration affected the accuracy of signal frequency and amplitude estimation. For long sampling durations, the sampling frequency equal to the Nyquist frequency was adequate for accurate signal frequency and amplitude estimation. Accuracy declined with decreasing sampling duration, especially for signal amplitude estimation with up to 40% standard deviation of normalized amplitude difference. To accurately estimate signal amplitude at low sampling duration, a sampling frequency of four times the signal frequency was necessary (two times the Nyquist frequency). Conclusions: The appropriate sampling frequency of accelerometers depends on the objective of the specific study and the characteristics of the behaviour. For studies with no constraints on device battery and storage, a sampling frequency of at least two times the Nyquist frequency will achieve relative optimal representative of signal information (i.e., frequency and amplitude). For classification and energy expenditure estimation of short-burst behaviours, 1.4 times the Nyquist frequency of behaviour is required.
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