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Hauser, P.

Publications and source records attributed to Hauser, P..

2 recordsLinked to original sources

Graph Lens Lite: An interactive biological network viewer for displaying, exploring, and sharing disease pathobiology and drug mechanism of action models

Biological network visualization together with graph-based analyses are key techniques in systems biology and network medicine to detect patterns and generate hypotheses regarding disease pathobiology, drug target identification, biomarker prioritization, and digital drug discovery. Network representations provide an intuitive way to communicate and share research findings. We have developed Graph Lens Lite, a browser-based tool that combines rich visualization with a streamlined interface for exploring and sharing biological networks. It offers an expressive query language, topological network analysis, interactive filtering, visual grouping, customizable layouts, a data editor, fine-grained property-based styling, animated edge-flow visualization, community detection, and a context-aware locally powered AI assistant particularly suited for exploring molecular models of disease pathobiology or drug mechanism of action. We demonstrate its utility on a curated network model of autosomal dominant polycystic kidney disease. Graph Lens Lite is open source, with a live web version available at https://delta4ai.github.io/GraphLensLite/.

bioinformatics↗

Mechanisms of surface antigenic variation in the human pathogenic fungus Pneumocystis jirovecii

Microbial pathogens commonly escape the human immune system by varying surface proteins. We investigated the mechanisms used for that purpose by Pneumocystis jirovecii. This uncultivable fungus is an obligate pulmonary pathogen which causes pneumonia in immuno-compromised individuals, a major life-threatening infection. Long-read PacBio sequencing was used to assemble a core of subtelomeres of a single P. jirovecii strain from a bronchoalveolar lavage fluid specimen of a single patient. A total of 113 genes encoding surface proteins were identified, including 28 pseudogenes. These genes formed a subtelomeric gene superfamily which included five families encoding adhesive GPI-anchored glycoproteins, and one family encoding excreted glycoproteins. Numerical analyses suggested that diversification of the glycoproteins relies on mosaic genes created by ectopic recombination, and occurs only within each family. DNA motifs suggested that all genes are expressed independently, except those of the family encoding the most abundant surface glycoproteins which are subject to mutually exclusive expression. PCR analyses showed that exchange of the expressed gene of the latter family occurs frequently, possibly favoured by the location of the genes proximal to the telomere because this allows concomitant telomere exchange. Our observations suggest that (i) P. jirovecii cell surface is made of a complex mixture of different surface proteins, with a majority of a single isoform of the most abundant glycoprotein, (ii) genetic mosaicism within each family ensures variation of the glycoproteins, and (iii) the strategy of the fungus consists in the continuous production of new subpopulations composed of cells which are antigenically different.

microbiology↗