Molecular mechanisms of lower-grade (II–III) diffuse gliomas (LGG) are still poorly understood, mainly because of their heterogeneity. They split into astrocytoma- (IDH-A) and oligodendroglioma-like (IDH-O) tumors both carrying mutations(s) at the isocitrate dehydrogenase (IDH) gene and into IDH wild type (IDH-wt) gliomas of glioblastoma resemblance. We generated detailed maps of the transcriptomes and DNA methylomes, revealing that cell functions divided into three major archetypic hallmarks: (i) increased proliferation in IDH-wt and, to a lesser degree, IDH-O; (ii) increased inflammation in IDH-A and IDH-wt; and (iii) the loss of synaptic transmission in all subtypes. Immunogenic properties of IDH-A are diverse, partly resembling signatures observed in grade IV mesenchymal glioblastomas or in grade I pilocytic astrocytomas. We analyzed details of coregulation between gene expression and DNA methylation and of the immunogenic micro-environment presumably driving tumor development and treatment resistance. Our transcriptome and methylome maps support personalized, case-by-case views to decipher the heterogeneity of glioma states in terms of data portraits. Thereby, molecular cartography provides a graphical coordinate system that links gene-level information with glioma subtypes, their phenotypes, and clinical context.

Surveillance of the evolving SARS-CoV-2 genome combined with epidemiological monitoring and emerging vaccination became paramount tasks to control the pandemic which is rapidly changing in time and space. Genomic surveillance must combine generation and sharing sequence data with appropriate bioinformatics monitoring and analysis methods. We applied molecular portrayal using self-organizing maps machine learning (SOM portrayal) to characterize the diversity of the virus genomes, their mutual relatedness and development since the beginning of the pandemic. The genetic landscape obtained visualizes the relevant mutations in a lineage-specific fashion and provides developmental paths in genetic state space from early lineages towards the variants of concern alpha, beta, gamma and delta. The different genes of the virus have specific footprints in the landscape reflecting their biological impact. SOM portrayal provides a novel option for ‘bioinformatics surveillance’ of the pandemic, with strong odds regarding visualization, intuitive perception and ‘personalization’ of the mutational patterns of the virus genomes.

Drug repositioning can save considerable time and resources and significantly speed up the drug development process. The increasing availability of drug action and disease-associated transcriptome data makes it an attractive source for repositioning studies. Here, we have developed a transcriptome-guided approach for drug/biologics repositioning based on multi-layer self-organizing maps (ml-SOM). It allows for analyzing multiple transcriptome datasets by segmenting them into layers of drug action- and disease-associated transcriptome data. A comparison of expression changes in clusters of functionally related genes across the layers identifies “drug target” spots in disease layers and evaluates the repositioning possibility of a drug. The repositioning potential for two approved biologics drugs (infliximab and brodalumab) confirmed the drugs’ action for approved diseases (ulcerative colitis and Crohn’s disease for infliximab and psoriasis for brodalumab). We showed the potential efficacy of infliximab for the treatment of sarcoidosis, but not chronic obstructive pulmonary disease (COPD). Brodalumab failed to affect dysregulated functional gene clusters in Crohn’s disease (CD) and systemic juvenile idiopathic arthritis (SJIA), clearly indicating that it may not be effective in the treatment of these diseases. In conclusion, ml-SOM offers a novel approach for transcriptome-guided drug repositioning that could be particularly useful for biologics drugs.

Single-cell RNA sequencing has become a standard technique to characterize tissue development. Hereby, cross-sectional snapshots of the diversity of cell transcriptomes were transformed into (pseudo-) longitudinal trajectories of cell differentiation using computational methods, which are based on similarity measures distinguishing cell phenotypes. Cell development is driven by alterations of transcriptional programs e.g., by differentiation from stem cells into various tissues or by adapting to micro-environmental requirements. We here complement developmental trajectories in cell-state space by trajectories in gene-state space to more clearly address this latter aspect. Such trajectories can be generated using self-organizing maps machine learning. The method transforms multidimensional gene expression patterns into two dimensional data landscapes, which resemble the metaphoric Waddington epigenetic landscape. Trajectories in this landscape visualize transcriptional programs passed by cells along their developmental paths from stem cells to differentiated tissues. In addition, we generated developmental “vector fields” using RNA-velocities to forecast changes of RNA abundance in the expression landscapes. We applied the method to tissue development of planarian as an illustrative example. Gene-state space trajectories complement our data portrayal approach by (pseudo-)temporal information about changing transcriptional programs of the cells. Future applications can be seen in the fields of tissue and cell differentiation, ageing and tumor progression and also, using other data types such as genome, methylome, and also clinical and epidemiological phenotype data.

Coeliac disease (CD) is a clinically heterogeneous autoimmune disease with variable presentation and progression triggered by gluten intake. Molecular or genetic factors contribute to disease heterogeneity, but the reasons for different outcomes are poorly understood. Transcriptome studies of tissue biopsies from CD patients are scarce. Here, we present a high-resolution analysis of the transcriptomes extracted from duodenal biopsies of 24 children and adolescents with active CD and 21 individuals without CD but with intestinal afflictions as controls. The transcriptomes of CD patients divide into three groups—a mixed group presenting the control cases, and CD-low and CD-high groups referring to lower and higher levels of CD severity. Persistence of symptoms was weakly associated with subgroup, but the highest marsh stages were present in subgroup CD-high, together with the highest cell cycle rates as an indicator of virtually complete villous atrophy. Considerable variation in inflammation-level between subgroups was further deciphered into immune cell types using cell type de-convolution. Self-organizing maps portrayal was applied to provide high-resolution landscapes of the CD-transcriptome. We find asymmetric patterns of miRNA and long non-coding RNA and discuss the effect of epigenetic regulation. Expression of genes involved in interferon gamma signaling represent suitable markers to distinguish CD from non-CD cases. Multiple pathways overlay in CD biopsies in different ways, giving rise to heterogeneous transcriptional patterns, which potentially provide information about etiology and the course of the disease.

Background: The blood transcriptome is expected to provide a detailed picture of an organism’s physiological state with potential outcomes for applications in medical diagnostics and molecular and epidemiological research.We here present the analysis of blood specimens of 3,388 adult individuals, together with phenotype characteristics such as disease history, medication status, lifestyle factors, and body mass index (BMI). The size and heterogeneity of this data challenges analytics in terms of dimension reduction, knowledge mining, feature extraction, and data integration. Methods: Self-organizing maps (SOM)-machine learning was applied to study transcriptional states on a population-wide scale. This method permits a detailed description and visualization of the molecular heterogeneity of transcriptomes and of their association with different phenotypic features. Results: The diversity of transcriptomes is described by personalized SOM-portraits, which specify the samples in terms of modules of co-expressed genes of different functional context. We identified two major blood transcriptome types where type 1 was found more in men, the elderly, and overweight people and it upregulated genes associated with inflammation and increased heme metabolism, while type 2 was predominantly found in women, younger, and normal weight participants and it was associated with activated immune responses, transcriptional, ribosomal, mitochondrial, and telomere-maintenance cell-functions. We find a striking overlap of signatures shared by multiple diseases, aging, and obesity driven by an underlying common pattern, which was associated with the immune response and the increase of inflammatory processes. Conclusions: Machine learning applications for large and heterogeneous omics data provide a holistic view on the diversity of the human blood transcriptome. It provides a tool for comparative analyses of transcriptional signatures and of associated phenotypes in population studies and medical applications.

No description available.

L’humanité fait l’expérience d’une période de crise systémique. En effet, la crise sanitaire du printemps 2020 soulève beaucoup d’incertitude dans la conduite à projet et remet en question les paradigmes existants. Pour répondre à ce contexte de crise, de nouvelles postures et pratiques sont nécessaires dans tous les domaines tels que le design. Dans l’optique d’explorer les dynamiques de réponse en contexte de crise, la réflexion porte sur le rôle du design dans la conduite à projet en de telles circonstances. La compétence du design mise de l’avant est la compétence de pouvoir agir/réagir à tout évènement, nouvelle situation lors de la réalisation d’un projet en contexte de crise La question à laquelle la présente recherche se propose de répondre est la suivante : « Comment et à quel niveau est-ce que le design intervient dans la conduite à projet en contexte de crise ? ». Pour répondre à cette question, le cadre théorique s’appuie sur les notions de design stratégique, de la conduite à projet et des dynamiques sociales de la collaboration et de la confiance. L’objectif principal de la recherche est d’identifier et de comprendre la compétence du design dynamisant la conduite d’un projet en contexte de crise et les pratiques associées. La présente recherche propose de répondre à cette question avec une approche méthodologique de l’étude du transitoire. L’approche méthodologique vise à observer, par l’entremise d’entretiens semi-dirigés et des observations participantes, la conduite du projet Visières. Le projet Visières est une réponse à la pénurie de visières médicales vécues lors de la crise du printemps 2020. Le parcours du projet et son évolution à la suite des différents problèmes rencontrés agissent à titre de vitrine sur le rôle du design dans la conduite à projet en contexte de crise. Les résultats de la présente recherche sur la compétence d’action et de réaction du design en contexte de crise avancent que la pratique de design du bricolage est la plus adaptée à la conduite à projet en temps de crise. De plus, pour favoriser le succès de la conduite à projet, la pratique du bricolage s’insère dans un cadre organisationnel agile et une conduite agile du projet. / Humanity is experiencing a period of systemic crisis. The crisis of spring 2020 revealed many disfunctions and established a climat of uncertainty over different sector of activity. To respond to this climat of crisis, new postures and practices are required; and design is no exception. In order to explore the dynamics of response to a crisis and the role of design, this research project is investigating the role of design in the conduct of project in a context of crisis. The key ability of design to act and react to any events, situations, actions that emerges during the conduct of a project in a time of crisis. This research is looking into answering the question: “How does design dynamize the conduct of project in a context of crisis and at which level?” In order to answer this question, theories of strategic design, project management and the dynamics of trust and cooperation are presented. The main objective of this research is to identify and understand the competency of design intervenes the conduct of project and the associated practices. This research looks to answer those questions through the case study of a crisis. Interviews and observations were conducted through the participation in the project Visières. The project Visières is a self-organizing response to the shortage of protective medical visor during the spring crisis of 2020. The course and the evolution of the project act as a showcase of the role of design in the conduct of project in times of crisis. The strategic design perspective is used to explore the position of design and its competency of adaptation as a key actor in societal transformation and emergency relief. The results of this research on the specific competency of design to act and react to events of a project promotes that the design practice of « bricolage » is the most suited to conduct a project in a context of crisis. Also, to support the success of the project, the practice of « bricolage » requires an agile environment, an agile organization and agile organizational practices.

Following the significant transition from the traditional production industry to an informationbased economy, the telecommunications industry was faced with an explosion of innovation, resulting in a continuous change in user behaviour. The industry has made efforts to adapt to a more datadriven future, which has given rise to larger and more complex systems. Therefore, troubleshooting systems such as anomaly detection and root cause analysis are essential features for maintaining service quality and facilitating daily operations. This study aims to explore the possibilities, benefits, and drawbacks of implementing cluster analysis for anomaly detection in hybrid fibercoaxial networks. Based on the literature review on unsupervised anomaly detection and an assumption regarding the anomalous behaviour in hybrid fibercoaxial network data, the kmeans, SelfOrganizing Map, and Gaussian Mixture Model were implemented both with and without Principal Component Analysis. Analysis of the results demonstrated an increase in performance for all models when the Principal Component Analysis was applied, with kmeans outperforming both SelfOrganizing Map and Gaussian Mixture Model. On this basis, it is recommended to apply Principal Component Analysis for clusteringbased anomaly detection. Further research is necessary to identify whether cluster analysis is the most appropriate unsupervised anomaly detection approach. / Följt av övergången från den traditionella tillverkningsindustrin till en informationsbaserad ekonomi stod telekommunikationsbranschen inför en explosion av innovation. Detta skifte resulterade i en kontinuerlig förändring av användarbeteende och branschen tvingades genomgå stora ansträngningar för att lyckas anpassa sig till den mer datadrivna framtiden. Större och mer komplexa system utvecklades och således blev felsökningsfunktioner såsom anomalidetektering och rotfelsanalys centrala för att upprätthålla servicekvalitet samt underlätta för den dagliga driftverksamheten. Syftet med studien är att utforska de möjligheterna, för- samt nackdelar med att använda klusteranalys för anomalidetektering inom HFC- nätverk. Baserat på litteraturstudien för oövervakad anomalidetektering samt antaganden för anomalibeteenden inom HFC- data valdes algritmerna k- means, Self- Organizing Map och Gaussian Mixture Model att implementeras, både med och utan Principal Component Analysis. Analys av resultaten påvisade en uppenbar ökning av prestanda för samtliga modeller vid användning av PCA. Vidare överträffade k- means, både Self- Organizing Maps och Gaussian Mixture Model. Utifrån resultatanalysen rekommenderas det således att PCA bör tillämpas vid klusterings- baserad anomalidetektering. Vidare är ytterligare forskning nödvändig för att avgöra huruvida klusteranalys är den mest lämpliga metoden för oövervakad anomalidetektering.

Network Direct Selling Organisations (NDSOs) exist in more than 50 countries and have more than 74 million members. The most recent statistical information reveals that the vast majority of members do not earn significant income. Criticism of these organisations revolves around the ethicality of consumption, the commercialisation of personal relationships, and the exploitation of unrealistic expectations. This study aims to explore how communication creates networks that sustain an industry of this kind despite the improbability of its existence. The study commences with a description of NDSOs from historical, operational, tactical, and strategic perspectives. Given the broader context created by the global presence of this industry, cybernetics has been selected as a meta-theoretical perspective for the study of communication. The more recent development of second-order cybernetics and social autopoiesis are introduced to communication theory as a field. Niklas Luhmann‟s new social theory of communication is assessed and applied in relation to existing communication theory. New conceptual models are developed to explore communication as the unity of the synthesis of information, utterance, understanding, and expectations as selections that occur both consciously and unconsciously, intentionally and unintentionally. These models indicate the multiplexity of individual and social operationally closed, yet informationally open systems, and they are used here to provide a systemic and coherent alternative to orthodox communication approaches to the study of organisations. The study adopts a constructivist epistemological stance and propounds throughout the necessity of further interdisciplinary collaboration. The study concludes that individuals are composite unities of self-creating systems, and they co-create social systems by self-creating and co-creating meaning. Meaning is described as the continuous virtualisation and actualisation of potentialities that in turn coordinate individual and social systems‟ actions. A communication process flow model is created to provide a theoretical explanation for the existence of NDSOs as self-creating systems. The study aims to show that communication has arguably become the most pervasive discipline as a result of the globally interactive era. It is shown that second-order cybernetics and social autopoiesis raise several further questions to be explored within communication theory as a field. / Communication, first-order cybernetics, second-order cybernetics, Complexity and complex systems, autopoiesis, self-reference, recursivity, operational closure, system boundaries, Network Direct Selling Organisations / Communication / D. Litt. et Phil. (Communication)