Tissue responses and host transcriptomics in bacterial infections

Bacterial infections can damage host tissue and are as such a potential threat to their hosts. To protect themselves from pathogens, hosts therefore can employ diverse immune reactions. When bacteria are recognized by their hosts, complex signaling cascades are triggered that lead to an in ux of specialized immune cells into the infected tissue and a change in tissue integrity. The in- ammation that is mounted may eliminate the pathogens, but will also cause substantial tissue damage. The foundation for the in ammatory process is laid early, in the rst 12 hours of infection. This thesis aims to reveal host responses within this early time frame. While in vitro studies can yield highly detailed data on subjects as proteinprotein and cell-bacterial interactions, they cannot reproduce all aspects that occur in a live animal, such as immune in ltration, nerve, and hormone e ects. We have developed a kidney infection model of bacterial infection to study early whole-host responses to bacteria. Using micropuncture techniques, we delivered bacteria to a known nephron, from where the infection progressed. Within hours, we observed numerous physiological changes of the tissue volume bordering the infection. Infection kinetics could be visualized and showed markedly faster host responses to haemolysin (Hly)-carrying bacteria compared to Hly-knockouts. Tissue oxygen levels decreased in response to infection, possibly caused both by blood ow restriction combined with epithelial oxygen consumption. Blood ow shutdown at the infected nephron was due to activation of the coagulation cascade. Coagulation also protected against sepsis, as animals died due to bacteremia when this cascade was inhibited. Some of these phenomena could be found in the host transcriptome. We also found that a core of common gene expression exists in live host innate immune responses by applying bioinformatic methods on the gene expression measurements. This core had a strong IFN-γ signature, a cytokine which we consequently found increased in the blood stream, and expressed by cells in the spleen. We go on to show that IFN-γ downregulates transcription of several neutrophil-attracting chemokines, and that this does not occur through canonical e ectors of either IFN-γ or in ammatory signaling pathways. The data I present here show that using a live host infection model can reveal host processes that cannot be found using in vitro models. By combining this model with analysis methods that yield detailed data, early responses could be studied. The data show the importance of live models for discovering unknown contributors and functions in in ammation, which may lead to possible future medicine development

The Molecular Tumor Board Portal supports clinical decisions and automated reporting for precision oncology

Cancer; Cancer geneticsCáncer; Genética del cáncerCàncer; Genètica del càncerThere is a growing need for systems that efficiently support the work of medical teams at the precision-oncology point of care. Here, we present the implementation of the Molecular Tumor Board Portal (MTBP), an academic clinical decision support system developed under the umbrella of Cancer Core Europe that creates a unified legal, scientific and technological platform to share and harness next-generation sequencing data. Automating the interpretation and reporting of sequencing results decrease the need for time-consuming manual procedures that are prone to errors. The adoption of an expert-agreed process to systematically link tumor molecular profiles with clinical actions promotes consistent decision-making and structured data capture across the connected centers. The use of information-rich patient reports with interactive content facilitates collaborative discussion of complex cases during virtual molecular tumor board meetings. Overall, streamlined digital systems like the MTBP are crucial to better address the challenges brought by precision oncology and accelerate the use of emerging biomarkers.Open access funding provided by Karolinska Institut

Support systems to guide clinical decision-making in precision oncology: The Cancer Core Europe Molecular Tumor Board Portal.

To the editor: the optimal management of cancer patients is increasingly dependent on individualized treatments guided by tumor sequencing data. As comprehensive genomic tests become routine in many disease settings and academic centers promote omics-guided clinical trial recruitment, accurate and scalable data interpretation represents a major challenge. The meticulous task of matching tumor alterations with approved or experimental therapies relies heavily on the expertise of each center

Comparative tissue transcriptomics reveal prompt inter-organ communication in response to local bacterial kidney infection

<p>Abstract</p> <p>Background</p> <p>Mucosal infections elicit inflammatory responses via regulated signaling pathways. Infection outcome depends strongly on early events occurring immediately when bacteria start interacting with cells in the mucosal membrane. Hitherto reported transcription profiles on host-pathogen interactions are strongly biased towards <it>in vitro </it>studies. To detail the local <it>in vivo </it>genetic response to infection, we here profiled host gene expression in a recent experimental model that assures high spatial and temporal control of uropathogenic <it>Escherichia coli </it>(UPEC) infection within the kidney of a live rat.</p> <p>Results</p> <p>Transcriptional profiling of tissue biopsies from UPEC-infected kidney tissue revealed 59 differentially expressed genes 8 h post-infection. Their relevance for the infection process was supported by a Gene Ontology (GO) analysis. Early differential expression at 3 h and 5 h post-infection was of low statistical significance, which correlated to the low degree of infection. Comparative transcriptomics analysis of the 8 h data set and online available studies of early local infection and inflammation defined a core of 80 genes constituting a "General tissue response to early local bacterial infections". Among these, 25% were annotated as interferon-γ (IFN-γ) regulated. Subsequent experimental analyses confirmed a systemic increase of IFN-γ in rats with an ongoing local kidney infection, correlating to splenic, rather than renal <it>Ifng </it>induction and suggested this inter-organ communication to be mediated by interleukin (IL)-23. The use of comparative transcriptomics allowed expansion of the statistical data handling, whereby relevant data could also be extracted from the 5 h data set. Out of the 31 differentially expressed core genes, some represented specific 5 h responses, illustrating the value of comparative transcriptomics when studying the dynamic nature of gene regulation in response to infections.</p> <p>Conclusion</p> <p>Our hypothesis-free approach identified components of infection-associated multi-cellular tissue responses and demonstrated how a comparative analysis allows retrieval of relevant information from lower-quality data sets. The data further define marked representation of IFN-γ responsive genes and a prompt inter-organ communication as a hallmark of an early local tissue response to infection.</p

The Molecular Tumor Board Portal supports clinical decisions and automated reporting for precision oncology.

There is a growing need for systems that efficiently support the work of medical teams at the precision-oncology point of care. Here, we present the implementation of the Molecular Tumor Board Portal (MTBP), an academic clinical decision support system developed under the umbrella of Cancer Core Europe that creates a unified legal, scientific and technological platform to share and harness next-generation sequencing data. Automating the interpretation and reporting of sequencing results decrease the need for time-consuming manual procedures that are prone to errors. The adoption of an expert-agreed process to systematically link tumor molecular profiles with clinical actions promotes consistent decision-making and structured data capture across the connected centers. The use of information-rich patient reports with interactive content facilitates collaborative discussion of complex cases during virtual molecular tumor board meetings. Overall, streamlined digital systems like the MTBP are crucial to better address the challenges brought by precision oncology and accelerate the use of emerging biomarkers

galaxyproteomics/docker-galaxyp: 17.09 release

:whale: Galaxy Docker repository with tools for proteomics (GalaxyP flavour

NBISweden/wgs-structvar: 1.1.3

Whole Genome Sequenceing Structural Variation Pipeline

Multi-omic data analysis using Galaxy

[Extract] Comprehensive multi-omic data acquisition has become a reality, largely driven by the\ud availability of high-throughput sequencing technologies for genomes and transcriptomes1,\ud and high-resolution mass spectrometry (MS)2,3 for the in-depth characterization of proteomes and metabolomes. Integrating genomic and proteomic data enables proteogenomic 4 and metaproteomic approaches 4, whereas integrating metabolomic and transcriptomic or proteomic data links biochemical activity profiles to expressed genes and proteins 6. Despite the potential for new discoveries, integrated analysis of raw multi-omic data is an often overlooked challenge 7, demanding the use of disparate software programs and requiring computational resources beyond the capacity of most biological research laboratories. For these reasons, multi-omic approaches remain out of reach for many. Here, we describe how Galaxy 8 can be used as one solution to this\ud problem