| 1. |
- Ovegård, Erik, et al.
(författare)
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Operational Guidance with Respect to Pure Loss of Stability and Parametric Rolling
- 2012
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Ingår i: Proceedings of the 11<sup>th</sup> International Conference on the Stability of Ships and Ocean Vehicles (STAB2012).
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Konferensbidrag (refereegranskat)abstract
- This paper reviews two previously presented simplified methods for assessment of pure loss of stability and parametric rolling based on linear signal theory. The methods are evaluated in relation to full-scale incidents and time-domain simulations. Underlying assumptions and tuning of the critical levels in the simplified methods with reference to time-domain simulations is discussed. Given proper tuning the methods are concluded to provide a feasible basis for ship specific on-board operational guidance.
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| 2. |
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| 3. |
- Rosén, Anders, et al.
(författare)
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Experience from Parametric Rolling of Ships
- 2012
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Ingår i: Parametric Resonance in Dynamical Systems. - New York, NY : Springer. - 9781461410423 ; , s. 147-165
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Bokkapitel (refereegranskat)abstract
- This chapter reviews three recent full-scale events with parametric rolling for Ro–Ro Large Car and Truck Carriers (LCTC). The events represent three principally different modes of parametric rolling: principal parametric resonance where the period of encounter is half of the roll natural period in following seas (I) and in head seas (II), and fundamental parametric resonance where the period of encounter coincides with the roll natural period in following seas (III). Roll motion, course, and speed recorded during the events are presented and analyzed together with the present weather situation based on recordings, forecasts, and re-analysis. Different aspects of on-board operational guidance for assisting crews in avoiding parametric rolling are discussed in relation to the presented events. Involved complexities and considerations that are normally not included in well defined model tests or numerical simulations are exposed.
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| 4. |
- Abdellah, Tebani, et al.
(författare)
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Integration of molecular profiles in a longitudinal wellness profiling cohort.
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies andimmune cell profiling, complementedwith gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.
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| 5. |
- Avican, Kemal, et al.
(författare)
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Reprogramming of Yersinia from Virulent to Persistent Mode Revealed by Complex In Vivo RNA-seq Analysis
- 2015
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Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- We recently found that Yersinia pseudotuberculosis can be used as a model of persistent bacterial infections. We performed in vivo RNA-seq of bacteria in small cecal tissue biopsies at early and persistent stages of infection to determine strategies associated with persistence. Comprehensive analysis of mixed RNA populations from infected tissues revealed that Y. pseudotuberculosis undergoes transcriptional reprogramming with drastic down-regulation of T3SS virulence genes during persistence when the pathogen resides within the cecum. At the persistent stage, the expression pattern in many respects resembles the pattern seen in vitro at 26oC, with for example, up-regulation of flagellar genes and invA. These findings are expected to have impact on future rationales to identify suitable bacterial targets for new antibiotics. Other genes that are up-regulated during persistence are genes involved in anaerobiosis, chemotaxis, and protection against oxidative and acidic stress, which indicates the influence of different environmental cues. We found that the Crp/CsrA/RovA regulatory cascades influence the pattern of bacterial gene expression during persistence. Furthermore, arcA, fnr, frdA, and wrbA play critical roles in persistence. Our findings suggest a model for the life cycle of this enteropathogen with reprogramming from a virulent to an adapted phenotype capable of persisting and spreading by fecal shedding.
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| 6. |
- Bengtsson-Palme, Johan, 1985, et al.
(författare)
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The human gut microbiome as a transporter of antibiotic resistance genes between continents
- 2015
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Ingår i: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 59:10, s. 6551-6560
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies of antibiotic resistance dissemination by travel have, by targeting only a select number of cultivable bacterial species, omitted most of the human microbiome. Here, we used explorative shotgun metagenomic sequencing to address the abundance of >300 antibiotic resistance genes in fecal specimens from 35 Swedish students taken before and after exchange programs on the Indian peninsula or in Central Africa. All specimens were additionally cultured for extended-spectrum beta-lactamase (ESBL)-producing enterobacteria, and the isolates obtained were genome sequenced. The overall taxonomic diversity and composition of the gut microbiome remained stable before and after travel, but there was an increasing abundance of Proteobacteria in 25/35 students. The relative abundance of antibiotic resistance genes increased, most prominently for genes encoding resistance to sulfonamide (2.6-fold increase), trimethoprim (7.7-fold), and beta-lactams (2.6-fold). Importantly, the increase observed occurred without any antibiotic intake. Of 18 students visiting the Indian peninsula, 12 acquired ESBL-producing Escherichia coli, while none returning from Africa were positive. Despite deep sequencing efforts, the sensitivity of metagenomics was not sufficient to detect acquisition of the low-abundant genes responsible for the observed ESBL phenotype. In conclusion, metagenomic sequencing of the intestinal microbiome of Swedish students returning from exchange programs in Central Africa or the Indian peninsula showed increased abundance of genes encoding resistance to widely used antibiotics.
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| 7. |
- Bersani, Cinzia, et al.
(författare)
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Genome-wide identification of Wig-1 mRNA targets by RIP-Seq analysis
- 2016
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Ingår i: Oncotarget. - : Impact Journals LLC. - 1949-2553. ; 7:2, s. 1895-1911
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Tidskriftsartikel (refereegranskat)abstract
- RNA-binding proteins (RBPs) play important roles in the regulation of gene expression through a variety of post-transcriptional mechanisms. The p53-induced RBP Wig-1 (Zmat3) binds RNA through its zinc finger domains and enhances stability of p53 and N-Myc mRNAs and decreases stability of FAS mRNA. To identify novel Wig-1-bound RNAs, we performed RNA-immunoprecipitation followed by high-throughput sequencing (RIP-Seq) in HCT116 and Saos-2 cells. We identified 286 Wig-1-bound mRNAs common between the two cell lines. Sequence analysis revealed that AU-rich elements (AREs) are highly enriched in the 3'UTR of these Wig-1-bound mRNAs. Network enrichment analysis showed that Wig-1 preferentially binds mRNAs involved in cell cycle regulation. Moreover, we identified a 2D Wig-1 binding motif in HIF1A mRNA. Our findings confirm that Wig-1 is an ARE-BP that regulates cell cycle-related processes and provide a novel view of how Wig-1 may bind mRNA through a putative structural motif. We also significantly extend the repertoire of Wig-1 target mRNAs. Since Wig-1 is a transcriptional target of the tumor suppressor p53, these results have implications for our understanding of p53-dependent stress responses and tumor suppression.
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| 8. |
- Boissin, Constance, et al.
(författare)
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Development and evaluation of deep learning algorithms for assessment of acute burns and the need for surgery
- 2023
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Assessment of burn extent and depth are critical and require very specialized diagnosis. Automated image-based algorithms could assist in performing wound detection and classification. We aimed to develop two deep-learning algorithms that respectively identify burns, and classify whether they require surgery. An additional aim assessed the performances in different Fitzpatrick skin types. Annotated burn (n = 1105) and background (n = 536) images were collected. Using a commercially available platform for deep learning algorithms, two models were trained and validated on 70% of the images and tested on the remaining 30%. Accuracy was measured for each image using the percentage of wound area correctly identified and F1 scores for the wound identifier; and area under the receiver operating characteristic (AUC) curve, sensitivity, and specificity for the wound classifier. The wound identifier algorithm detected an average of 87.2% of the wound areas accurately in the test set. For the wound classifier algorithm, the AUC was 0.885. The wound identifier algorithm was more accurate in patients with darker skin types; the wound classifier was more accurate in patients with lighter skin types. To conclude, image-based algorithms can support the assessment of acute burns with relatively good accuracy although larger and different datasets are needed.
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| 9. |
- Branca, Rui M. M., et al.
(författare)
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HiRIEF LC-MSMS enables deep proteome coverage and unbiased proteogenomics
- 2014
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Ingår i: Nature Methods. - 1548-7091 .- 1548-7105. ; 11:1, s. 59-
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Tidskriftsartikel (refereegranskat)abstract
- We present a liquid chromatography-mass spectrometry (LC-MSMS)-based method permitting unbiased (gene prediction-independent) genome-wide discovery of protein-coding loci in higher eukaryotes. Using high-resolution isoelectric focusing (HiRIEF) at the peptide level in the 3.7-5.0 pH range and accurate peptide isoelectric point (pI) prediction, we probed the six-reading-frame translation of the human and mouse genomes and identified 98 and 52 previously undiscovered protein-coding loci, respectively. The method also enabled deep proteome coverage, identifying 13,078 human and 10,637 mouse proteins.
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| 10. |
- Brownstein, Catherine A., et al.
(författare)
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An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge
- 2014
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:3, s. R53-
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.
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| 11. |
- Danielsson, Frida, et al.
(författare)
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Assessing the consistency of public human tissue RNA-seq data sets
- 2015
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Ingår i: Briefings in Bioinformatics. - : Oxford University Press. - 1467-5463 .- 1477-4054. ; 16:6, s. 941-949
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Tidskriftsartikel (refereegranskat)abstract
- Sequencing-based gene expression methods like RNA-sequencing (RNA-seq) have become increasingly common, but it is often claimed that results obtained in different studies are not comparable owing to the influence of laboratory batch effects, differences in RNA extraction and sequencing library preparation methods and bioinformatics processing pipelines. It would be unfortunate if different experiments were in fact incomparable, as there is great promise in data fusion and meta-analysis applied to sequencing data sets. We therefore compared reported gene expression measurements for ostensibly similar samples (specifically, human brain, heart and kidney samples) in several different RNA-seq studies to assess their overall consistency and to examine the factors contributing most to systematic differences. The same comparisons were also performed after preprocessing all data in a consistent way, eliminating potential bias from bioinformatics pipelines. We conclude that published human tissue RNA-seq expression measurements appear relatively consistent in the sense that samples cluster by tissue rather than laboratory of origin given simple preprocessing transformations. The article is supplemented by a detailed walkthrough with embedded R code and figures.
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| 12. |
- Danielsson, Frida, 1984-
(författare)
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Integration of RNA and protein expression profiles to study human cells
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cellular life is highly complex. In order to expand our understanding of the workings of human cells, in particular in the context of health and disease, detailed knowledge about the underlying molecular systems is needed. The unifying theme of this thesis concerns the use of data derived from sequencing of RNA, both within the field of transcriptomics itself and as a guide for further studies at the level of protein expression. In paper I, we showed that publicly available RNA-seq datasets are consistent across different studies, requiring only light processing for the data to cluster according to biological, rather than technical characteristics. This suggests that RNA-seq has developed into a reliable and highly reproducible technology, and that the increasing amount of publicly available RNA-seq data constitutes a valuable resource for meta-analyses. In paper II, we explored the ability to extrapolate protein concentrations by the use of RNA expression levels. We showed that mRNA and corresponding steady-state protein concentrations correlate well by introducing a gene-specific RNA-to-protein conversion factor that is stable across various cell types and tissues. The results from this study indicate the utility of RNA-seq also within the field of proteomics.The second part of the thesis starts with a paper in which we used transcriptomics to guide subsequent protein studies of the molecular mechanisms underlying malignant transformation. In paper III, we applied a transcriptomics approach to a cell model for defined steps of malignant transformation, and identified several genes with interesting expression patterns whose corresponding proteins were further analyzed with subcellular spatial resolution. Several of these proteins were further studied in clinical tumor samples, confirming that this cell model provides a relevant system for studying cancer mechanisms. In paper IV, we continued to explore the transcriptional landscape in the same cell model under moderate hypoxic conditions.To conclude, this thesis demonstrates the usefulness of RNA-seq data, from a transcriptomics perspective and beyond; to guide in analyses of protein expression, with the ultimate goal to unravel the complexity of the human cell, from a holistic point of view.
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| 13. |
- Danielsson, Frida, et al.
(författare)
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Majority of differentially expressed genes are down-regulated during malignant transformation in a four-stage model
- 2013
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 110:17, s. 6853-6858
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Tidskriftsartikel (refereegranskat)abstract
- The transformation of normal cells to malignant, metastatic tumor cells is a multistep process caused by the sequential acquirement of genetic changes. To identify these changes, we compared the transcriptomes and levels and distribution of proteins in a four-stage cell model of isogenically matched normal, immortalized, transformed, and metastatic human cells, using deep transcriptome sequencing and immunofluorescence microscopy. The data show that similar to 6% (n = 1,357) of the human protein-coding genes are differentially expressed across the stages in the model. Interestingly, the majority of these genes are down-regulated, linking malignant transformation to dedifferentiation. The up-regulated genes are mainly components that control cellular proliferation, whereas the down-regulated genes consist of proteins exposed on or secreted from the cell surface. As many of the identified gene products control basic cellular functions that are defective in cancers, the data provide candidates for follow-up studies to investigate their functional roles in tumor formation. When we further compared the expression levels of four of the identified proteins in clinical cancer cohorts, similar differences were observed between benign and cancer cells, as in the cell model. This shows that this comprehensive demonstration of the molecular changes underlying malignant transformation is a relevant model to study the process of tumor formation.
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| 14. |
- de la Paz Celorio-Mancera, Maria, 1978-, et al.
(författare)
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Evolutionary history of host use, rather than plant phylogeny, determines gene expression in a generalist butterfly
- 2016
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Ingår i: BMC Evolutionary Biology. - : Springer Science and Business Media LLC. - 1471-2148. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although most insect species are specialized on one or few groups of plants, there are phytophagous insects that seem to use virtually any kind of plant as food. Understanding the nature of this ability to feed on a wide repertoire of plants is crucial for the control of pest species and for the elucidation of the macroevolutionary mechanisms of speciation and diversification of insect herbivores. Here we studied Vanessa cardui, the species with the widest diet breadth among butterflies and a potential insect pest, by comparing tissue-specific transcriptomes from caterpillars that were reared on different host plants. We tested whether the similarities of gene-expression response reflect the evolutionary history of adaptation to these plants in the Vanessa and related genera, against the null hypothesis of transcriptional profiles reflecting plant phylogenetic relatedness. Result: Using both unsupervised and supervised methods of data analysis, we found that the tissue-specific patterns of caterpillar gene expression are better explained by the evolutionary history of adaptation of the insects to the plants than by plant phylogeny. Conclusion: Our findings suggest that V. cardui may use two sets of expressed genes to achieve polyphagy, one associated with the ancestral capability to consume Rosids and Asterids, and another allowing the caterpillar to incorporate a wide range of novel host-plants.
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| 15. |
- Fagerberg, Linn, et al.
(författare)
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Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics
- 2014
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 13:2, s. 397-406
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Tidskriftsartikel (refereegranskat)abstract
- Global classification of the human proteins with regards to spatial expression patterns across organs and tissues is important for studies of human biology and disease. Here, we used a quantitative transcriptomics analysis (RNA-Seq) to classify the tissue-specific expression of genes across a representative set of all major human organs and tissues and combined this analysis with antibody- based profiling of the same tissues. To present the data, we launch a new version of the Human Protein Atlas that integrates RNA and protein expression data corresponding to 80% of the human protein-coding genes with access to the primary data for both the RNA and the protein analysis on an individual gene level. We present a classification of all human protein-coding genes with regards to tissue-specificity and spatial expression pattern. The integrative human expression map can be used as a starting point to explore the molecular constituents of the human body.
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| 16. |
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| 17. |
- Hagey, Daniel W., et al.
(författare)
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Distinct transcription factor complexes act on a permissive chromatin landscape to establish regionalized gene expression in CNS stem cells
- 2016
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 26:7, s. 908-917
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Tidskriftsartikel (refereegranskat)abstract
- Spatially distinct gene expression profiles in neural stem cells (NSCs) are a prerequisite to the formation of neuronal diversity, but how these arise from the regulatory interactions between chromatin accessibility and transcription factor activity has remained unclear. Here, we demonstrate that, despite their distinct gene expression profiles, NSCs of the mouse cortex and spinal cord share the majority of their DNase I hypersensitive sites (DHSs). Regardless of this similarity, domain-specific gene expression is highly correlated with the relative accessibility of associated DHSs, as determined by sequence read density. Notably, the binding pattern of the general NSC transcription factor SOX2 is also largely cell type specific and coincides with an enrichment of LHX2 motifs in the cortex and HOXA9 motifs in the spinal cord. Interestingly, in a zebrafish reporter gene system, these motifs were critical determinants of patterned gene expression along the rostral-caudal axis. Our findings establish a predictive model for patterned NSC gene expression, whereby domain-specific expression of LHX2 and HOX proteins act on their target motifs within commonly accessible cis-regulatory regions to specify SOX2 binding. In turn, this binding correlates strongly with these DHSs relative accessibility-a robust predictor of neighboring gene expression.
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| 18. |
- Hallén, Kristofer, et al.
(författare)
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mGluR-Mediated calcium oscillations in the lamprey: a computational model
- 2004
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Ingår i: Neurocomputing. - AMSTERDAM : Elsevier BV. - 0925-2312 .- 1872-8286. ; 58-60, s. 431-435, s. 431-435
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Tidskriftsartikel (refereegranskat)abstract
- Slow Ca2+ oscillations caused by release from intracellular stores have been observed in neurons in the lamprey spinal cord. These oscillations are triggered by activation of metabotropic glutamate receptors on the cell surface. The pathway leading from receptor activation to the inositol triphosphate-mediated release of Ca2+ from the endoplasmatic reticulum has been modelled in order to facilitate further understanding of the nature of these oscillations. The model generates Ca2+ oscillations with a frequency range of 0.01–0.09 Hz. A prediction of the model is that the frequency will increase with a stronger extracellular glutamate signal.
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| 19. |
- Hasmats, Johanna, et al.
(författare)
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Assessment of Whole Genome Amplification for Sequence Capture and Massively Parallel Sequencing
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:1, s. e84785-
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Tidskriftsartikel (refereegranskat)abstract
- Exome sequence capture and massively parallel sequencing can be combined to achieve inexpensive and rapid global analyses of the functional sections of the genome. The difficulties of working with relatively small quantities of genetic material, as may be necessary when sharing tumor biopsies between collaborators for instance, can be overcome using whole genome amplification. However, the potential drawbacks of using a whole genome amplification technology based on random primers in combination with sequence capture followed by massively parallel sequencing have not yet been examined in detail, especially in the context of mutation discovery in tumor material. In this work, we compare mutations detected in sequence data for unamplified DNA, whole genome amplified DNA, and RNA originating from the same tumor tissue samples from 16 patients diagnosed with non-small cell lung cancer. The results obtained provide a comprehensive overview of the merits of these techniques for mutation analysis. We evaluated the identified genetic variants, and found that most (74%) of them were observed in both the amplified and the unamplified sequence data. Eighty-nine percent of the variations found by WGA were shared with unamplified DNA. We demonstrate a strategy for avoiding allelic bias by including RNA-sequencing information.
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| 20. |
- Hasmats, Johanna, et al.
(författare)
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Validation of whole genome amplification for analysis of the p53 tumor suppressor gene in limited amounts of tumor samples
- 2012
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 425:2, s. 379-383
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Tidskriftsartikel (refereegranskat)abstract
- Personalized cancer treatment requires molecular characterization of individual tumor biopsies. These samples are frequently only available in limited quantities hampering genomic analysis. Several whole genome amplification (WGA) protocols have been developed with reported varying representation of genomic regions post amplification. In this study we investigate region dropout using a 929 polymerase based WGA approach. DNA from 123 lung cancers specimens and corresponding normal tissue were used and evaluated by Sanger sequencing of the p53 exons 5-8. To enable comparative analysis of this scarce material, WGA samples were compared with unamplified material using a pooling strategy of the 123 samples. In addition, a more detailed analysis of exon 7 amplicons were performed followed by extensive cloning and Sanger sequencing. Interestingly, by comparing data from the pooled samples to the individually sequenced exon 7, we demonstrate that mutations are more easily recovered from WGA pools and this was also supported by simulations of different sequencing coverage. Overall this data indicate a limited random loss of genomic regions supporting the use of whole genome amplification for genomic analysis.
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| 21. |
- Holme, Petter, et al.
(författare)
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Atmospheric Reaction Systems as Null-Models to Identify Structural Traces of Evolution in Metabolism
- 2011
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:5, s. e19759-
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Tidskriftsartikel (refereegranskat)abstract
- The metabolism is the motor behind the biological complexity of an organism. One problem of characterizing its large-scale structure is that it is hard to know what to compare it to. All chemical reaction systems are shaped by the same physics that gives molecules their stability and affinity to react. These fundamental factors cannot be captured by standard null-models based on randomization. The unique property of organismal metabolism is that it is controlled, to some extent, by an enzymatic machinery that is subject to evolution. In this paper, we explore the possibility that reaction systems of planetary atmospheres can serve as a null-model against which we can define metabolic structure and trace the influence of evolution. We find that the two types of data can be distinguished by their respective degree distributions. This is especially clear when looking at the degree distribution of the reaction network (of reaction connected to each other if they involve the same molecular species). For the Earth's atmospheric network and the human metabolic network, we look into more detail for an underlying explanation of this deviation. However, we cannot pinpoint a single cause of the difference, rather there are several concurrent factors. By examining quantities relating to the modular-functional organization of the metabolism, we confirm that metabolic networks have a more complex modular organization than the atmospheric networks, but not much more. We interpret the more variegated modular arrangement of metabolism as a trace of evolved functionality. On the other hand, it is quite remarkable how similar the structures of these two types of networks are, which emphasizes that the constraints from the chemical properties of the molecules has a larger influence in shaping the reaction system than does natural selection.
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| 22. |
- Holme, Petter, et al.
(författare)
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Subnetwork hierarchies of biochemical pathways
- 2003
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 19:4, s. 532-538
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Tidskriftsartikel (refereegranskat)abstract
- Motivation: The vastness and complexity of the biochemical networks that have been mapped out by modern genomics calls for decomposition into subnetworks. Such networks can have inherent non-local features that require the global structure to be taken into account in the decomposition procedure. Furthermore, basic questions such as to what extent the network (graph theoretically) can be said to be built by distinct subnetworks are little studied. Results: We present a method to decompose biochemical networks into subnetworks based on the global geometry of the network. This method enables us to analyze the full hierarchical organization of biochemical networks and is applied to 43 organisms from the WIT database. Two types of biochemical networks are considered: metabolic networks and whole-cellular networks (also including for example information processes). Conceptual and quantitative ways of describing the hierarchical ordering are discussed. The general picture of the metabolic networks arising from our study is that of a few core-clusters centred around the most highly connected substances enclosed by other substances in outer shells, and a few other well-defined subnetworks.
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| 23. |
- Holme, Petter, et al.
(författare)
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Substance networks are optimal simple-graph representations of metabolism
- 2010
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Ingår i: Chinese Science Bulletin. - : Springer. - 1001-6538 .- 1861-9541. ; 55:27-28, s. 3161-3168
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Tidskriftsartikel (refereegranskat)abstract
- One approach to study the system-wide organization of biochemistry is to use statistical graph theory. In such heavily simplified methods, which disregard most of the dynamic aspects of biochemistry, one is faced with fundamental questions. One such question is how the chemical reaction systems should be reduced to a graph retaining as much functional information as possible from the original reaction system. In these graph representations, should the edges go between substrates and products, or substrates and substrates, or both? Should vertices represent substances or reactions? Different representations encode different information about the reaction system and affect network measures in different ways. This paper investigates which representation reflects the functional organization of the metabolic system in the best way, according to the defined criteria. Four different graph representations of metabolism (three where the vertices are metabolites, one where the vertices are reactions) are evaluated using data from different organisms and databases. The graph representations are evaluated by comparing the overlap between clusters (network modules) and annotated functions, and also by comparing the set of identified currency metabolites with those that other authors have identified using qualitative biological arguments. It is found that a “substance network”, where all metabolites participating in a reaction are connected, is better than others, evaluated with respect to both the functional overlap between modules and functions and to the number and identity of the identified currency metabolites.
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| 24. |
- Holme, Petter, et al.
(författare)
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Understanding and Exploiting Information Spreading and Integrating Technologies
- 2011
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Ingår i: Journal of Computer Science and Technology. - : Springer Science and Business Media LLC. - 1000-9000 .- 1860-4749. ; 26:5, s. 829-836
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Tidskriftsartikel (refereegranskat)abstract
- Our daily life leaves an increasing amount of digital traces, footprints that are improving our lives. Data-mining tools, like recommender systems, convert these traces to information for aiding decisions in an ever-increasing number of areas in our lives. The feedback loop from what we do, to the information this produces, to decisions what to do next, will likely be an increasingly important factor in human behavior on all levels from individuals to societies. In this essay, we review some effects of this feedback and discuss how to understand and exploit them beyond mapping them on more well-understood phenomena. We take examples from models of spreading phenomena in social media to argue that analogies can be deceptive, instead we need to fresh approaches to the new types of data, something we exemplify with promising applications in medicine.
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| 25. |
- Hu, Yue O. O., et al.
(författare)
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Stationary and portable sequencing-based approaches for tracing wastewater contamination in urban stormwater systems
- 2018
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Urban sewer systems consist of wastewater and stormwater sewers, of which only wastewater is processed before being discharged. Occasionally, misconnections or damages in the network occur, resulting in untreated wastewater entering natural water bodies via the stormwater system. Cultivation of faecal indicator bacteria (e.g. Escherichia coli; E. coli) is the current standard for tracing wastewater contamination. This method is cheap but has limited specificity and mobility. Here, we compared the E. coli culturing approach with two sequencing-based methodologies (Illumina MiSeq 16S rRNA gene amplicon sequencing and Oxford Nanopore MinION shotgun metagenomic sequencing), analysing 73 stormwater samples collected in Stockholm. High correlations were obtained between E. coli culturing counts and frequencies of human gut microbiome amplicon sequences, indicating E. coli is indeed a good indicator of faecal contamination. However, the amplicon data further holds information on contamination source or alternatively how much time has elapsed since the faecal matter has entered the system. Shotgun metagenomic sequencing on a subset of the samples using a portable real-time sequencer, MinION, correlated well with the amplicon sequencing data. This study demonstrates the use of DNA sequencing to detect human faecal contamination in stormwater systems and the potential of tracing faecal contamination directly in the field.
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