| 1. |
- Ahrén, Dag, et al.
(författare)
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PHOREST: a web-based tool for comparative analyses of expressed sequence tag data
- 2004
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Ingår i: Molecular Ecology Notes. - : Wiley. - 1471-8278 .- 1471-8286. ; 4:2, s. 311-314
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Tidskriftsartikel (refereegranskat)abstract
- Comparative analysis of expressed sequence tags is becoming an important tool in molecular ecology for comparing gene expression in organisms grown in certain environments. Additionally, expressed sequence tag database information can be used for the construction of DNA microarrays and for the detection of single nucleotide polymorphisms. For such applications, we present PHOREST, a web-based tool for managing, analysing and comparing various collections of expressed sequence tags. It is written in PHP (PHP: Hypertext Preprocessor) and runs on UNIX, Microsoft Windows and Macintosh (Mac OS X) platforms.
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| 2. |
- Andersson, Emil, et al.
(författare)
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Facilitating clinically relevant skin tumor diagnostics with spectroscopy-driven machine learning
- 2024
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Ingår i: iScience. - 2589-0042. ; 27:5
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Tidskriftsartikel (refereegranskat)abstract
- In the dawning era of artificial intelligence (AI), health care stands to undergo a significant transformation with the increasing digitalization of patient data. Digital imaging, in particular, will serve as an important platform for AI to aid decision making and diagnostics. A growing number of studies demonstrate the potential of automatic pre-surgical skin tumor delineation, which could have tremendous impact on clinical practice. However, current methods rely on having ground truth images in which tumor borders are already identified, which is not clinically possible. We report a novel approach where hyperspectral images provide spectra from small regions representing healthy tissue and tumor, which are used to generate prediction maps using artificial neural networks (ANNs), after which a segmentation algorithm automatically identifies the tumor borders. This circumvents the need for ground truth images, since an ANN model is trained with data from each individual patient, representing a more clinically relevant approach.
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| 3. |
- Breslin, Thomas, et al.
(författare)
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Signal transduction pathway profiling of individual tumor samples
- 2005
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Ingår i: BMC Bioinformatics. - : Springer Science and Business Media LLC. - 1471-2105. ; 6:163
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Tidskriftsartikel (refereegranskat)abstract
- Background Signal transduction pathways convey information from the outside of the cell to transcription factors, which in turn regulate gene expression. Our objective is to analyze tumor gene expression data from microarrays in the context of such pathways. Results We use pathways compiled from the TRANSPATH/TRANSFAC databases and the literature, and three publicly available cancer microarray data sets. Variation in pathway activity, across the samples, is gauged by the degree of correlation between downstream targets of a pathway. Two correlation scores are applied; one considers all pairs of downstream targets, and the other considers only pairs without common transcription factors. Several pathways are found to be differentially active in the data sets using these scores. Moreover, we devise a score for pathway activity in individual samples, based on the average expression value of the downstream targets. Statistical significance is assigned to the scores using permutation of genes as null model. Hence, for individual samples, the status of a pathway is given as a sign, + or -, and a p-value. This approach defines a projection of high-dimensional gene expression data onto low-dimensional pathway activity scores. For each dataset and many pathways we find a much larger number of significant samples than expected by chance. Finally, we find that several sample-wise pathway activities are significantly associated with clinical classifications of the samples. Conclusion This study shows that it is feasible to infer signal transduction pathway activity, in individual samples, from gene expression data. Furthermore, these pathway activities are biologically relevant in the three cancer data sets.
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| 4. |
- Chickarmane, Vijay, et al.
(författare)
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Transcriptional dynamics of the embryonic stem cell switch
- 2006
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Ingår i: PLoS Computational Biology. - : Public Library of Science (PLoS). - 1553-7358. ; 2:9, s. 1080-1092
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Tidskriftsartikel (refereegranskat)abstract
- Recent ChIP experiments of human and mouse embryonic stem cells have elucidated the architecture of the transcriptional regulatory circuitry responsible for cell determination, which involves the transcription factors OCT4, SOX2, and NANOG. In addition to regulating each other through feedback loops, these genes also regulate downstream target genes involved in the maintenance and differentiation of embryonic stem cells. A search for the OCT4-SOX2-NANOG network motif in other species reveals that it is unique to mammals. With a kinetic modeling approach, we ascribe function to the observed OCT4-SOX2-NANOG network by making plausible assumptions about the interactions between the transcription factors at the gene promoter binding sites and RNA polymerase (RNAP), at each of the three genes as well as at the target genes. We identify a bistable switch in the network, which arises due to several positive feedback loops, and is switched ON/OFF by input environmental signals. The switch stabilizes the expression levels of the three genes, and through their regulatory roles on the downstream target genes, leads to a binary decision: when OCT4, SOX2, and NANOG are expressed and the switch is ON, the self-renewal genes are ON and the differentiation genes are OFF. The opposite holds when the switch is OFF. The model is extremely robust to parameter changes. In addition to providing a self-consistent picture of the transcriptional circuit, the model generates several predictions. Increasing the binding strength of NANOG to OCT4 and SOX2, or increasing its basal transcriptional rate, leads to an irreversible bistable switch: the switch remains ON even when the activating signal is removed. Hence, the stem cell can be manipulated to be self-renewing without the requirement of input signals. We also suggest tests that could discriminate between a variety of feedforward regulation architectures of the target genes by OCT4, SOX2, and NANOG.
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| 5. |
- De Beeck, Michiel Op, et al.
(författare)
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Elucidating fungal decomposition of organic matter at sub-micrometer spatial scales using optical photothermal infrared (O-PTIR) microspectroscopy
- 2024
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Ingår i: Applied and Environmental Microbiology. - 0099-2240. ; 90:2
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Tidskriftsartikel (refereegranskat)abstract
- In microbiological studies, a common goal is to link environmental factors to microbial activities. Both environmental factors and microbial activities are typically derived from bulk samples. It is becoming increasingly clear that such bulk environmental parameters poorly represent the microscale environments microorganisms experience. Using infrared (IR) microspectroscopy, the spatial distribution of chemical compound classes can be visualized, making it a useful tool for studying the interactions between microbial cells and their microenvironments. The spatial resolution of conventional IR microspectroscopy has been limited by the diffractionlimit of IR light. The recent development of optical photothermal infrared (O-PTIR) microspectroscopy has pushed the spatial resolution of IR microspectroscopy beyond this diffractionlimit, allowing the distribution of chemical compound classes to be visualized at sub-micrometer spatial scales. To examine the potential and limitations of O-PTIR microspectroscopy to probe the interactions between fungal cells and their immediate environments, we imaged the decomposition of cellulose filmsby cells of the ectomycorrhizal fungus Paxillus involutus and compared O-PTIR results using conventional IR microspectroscopy. Whereas the data collected with conventional IR microspectroscopy indicated that P. involutus has only a very limited ability to decompose cellulose films,O-PTIR data suggested that the ability of P. involutus to decompose cellulose was substantial. Moreover, the O-PTIR method enabled the identificationof a zone located outside the fungal hyphae where the cellulose was decomposed by oxidation. We conclude that O-PTIR can provide valuable new insights into the abilities and mechanisms by which microorganisms interact with their surrounding environments.
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| 6. |
- Dixon, Laura E., et al.
(författare)
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Light and circadian regulation of clock components aids flexible responses to environmental signals
- 2014
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Ingår i: New Phytologist. - : Wiley. - 1469-8137 .- 0028-646X. ; 203:2, s. 568-577
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Tidskriftsartikel (refereegranskat)abstract
- The circadian clock measures time across a 24h period, increasing fitness by phasing biological processes to the most appropriate time of day. The interlocking feedback loop mechanism of the clock is conserved across species; however, the number of loops varies. Mathematical and computational analyses have suggested that loop complexity affects the overall flexibility of the oscillator, including its responses to entrainment signals. We used a discriminating experimental assay, at the transition between different photoperiods, in order to test this proposal in a minimal circadian network (in Ostreococcus tauri) and a more complex network (in Arabidopsis thaliana). Transcriptional and translational reporters in O.tauri primarily tracked dawn or dusk, whereas in A.thaliana, a wider range of responses were observed, consistent with its more flexible clock. Model analysis supported the requirement for this diversity of responses among the components of the more complex network. However, these and earlier data showed that the O.tauri network retains surprising flexibility, despite its simple circuit. We found that models constructed from experimental data can show flexibility either from multiple loops and/or from multiple light inputs. Our results suggest that O.tauri has adopted the latter strategy, possibly as a consequence of genomic reduction.
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| 7. |
- Fogelmark, Karl, et al.
(författare)
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Rethinking transcriptional activation in the Arabidopsis circadian clock.
- 2014
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Ingår i: PLoS Computational Biology. - : Public Library of Science (PLoS). - 1553-7358. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Circadian clocks are biological timekeepers that allow living cells to time their activity in anticipation of predictable daily changes in light and other environmental factors. The complexity of the circadian clock in higher plants makes it difficult to understand the role of individual genes or molecular interactions, and mathematical modelling has been useful in guiding clock research in model organisms such as Arabidopsis thaliana. We present a model of the circadian clock in Arabidopsis, based on a large corpus of published time course data. It appears from experimental evidence in the literature that most interactions in the clock are repressive. Hence, we remove all transcriptional activation found in previous models of this system, and instead extend the system by including two new components, the morning-expressed activator RVE8 and the nightly repressor/activator NOX. Our modelling results demonstrate that the clock does not need a large number of activators in order to reproduce the observed gene expression patterns. For example, the sequential expression of the PRR genes does not require the genes to be connected as a series of activators. In the presented model, transcriptional activation is exclusively the task of RVE8. Predictions of how strongly RVE8 affects its targets are found to agree with earlier interpretations of the experimental data, but generally we find that the many negative feedbacks in the system should discourage intuitive interpretations of mutant phenotypes. The dynamics of the clock are difficult to predict without mathematical modelling, and the clock is better viewed as a tangled web than as a series of loops.
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| 8. |
- Fogelmark, Karl, et al.
(författare)
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Selection Shapes Transcriptional Logic and Regulatory Specialization in Genetic Networks.
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:2
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Tidskriftsartikel (refereegranskat)abstract
- Living organisms need to regulate their gene expression in response to environmental signals and internal cues. This is a computational task where genes act as logic gates that connect to form transcriptional networks, which are shaped at all scales by evolution. Large-scale mutations such as gene duplications and deletions add and remove network components, whereas smaller mutations alter the connections between them. Selection determines what mutations are accepted, but its importance for shaping the resulting networks has been debated.
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| 9. |
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| 10. |
- Holzgräfe, Christian, et al.
(författare)
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Mutation-induced fold switching among lattice proteins.
- 2011
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 135:19
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Tidskriftsartikel (refereegranskat)abstract
- Recent experiments uncovered a mutational pathway between two proteins, along which a single mutation causes a switch in fold. Searching for such paths between real proteins remains, despite this achievement, a true challenge. Here, we analyze fold switching in the minimalistic hydrophobic/polar model on a square lattice. For this analysis, we generate a comprehensive sequence-structure database for chains of length ≤ 30, which exceeds previous work by five units. Single-mutation-induced fold switching turns out to be quite common in the model. The switches define a fold network, whose topology is roughly similar to what one would expect for a set of randomly connected nodes. In the combinatorially challenging search for fold switches between two proteins, a tempting strategy is to only consider paths containing the minimum number of mutations. Such a restricted search fails to correctly identify 40% of the single-mutation-linked fold pairs that we observe. The thermodynamic stability is correlated with mutational stability and is, on average, markedly reduced at the observed fold switches.
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