Diffuse leptomeningeal glioneuronal tumour (DLGNT) in children: the emerging role of genomic analysis

Diffuse leptomeningeal glioneuronal tumours (DLGNT) represent rare enigmatic CNS tumours of childhood. Most patients with this disease share common radiological and histopathological features but the clinical course of this disease is variable. A radiological hallmark of this disease is widespread leptomeningeal enhancement that may involve the entire neuroaxis with predilection for the posterior fossa and spine. The classic pathologic features include low- to moderate-density cellular lesions with OLIG2 expression and evidence of ‘oligodendroglioma-like’ appearance. The MAPK/ERK signaling pathway has recently been reported as a potential driver of tumourigenesis in up to 80% of DLGNT with KIAA1549:BRAF fusions being the most common event seen. Until now, limited analysis of the biological drivers of tumourigenesis has been undertaken via targeted profiling, chromosomal analysis and immunohistochemistry. Our study represents the first examples of comprehensive genomic sequencing in DLGNT and shows that it is not only feasible but crucial to our understanding of this rare disease. Moreover, we demonstrate that DLGNT may be more genomically complex than single-event MAPK/ERK signaling pathway tumours.

On sample preparation methods for fermented beverage VOCs profiling by GCxGC-TOFMS

Introduction Aromas and tastes have crucial influences on the quality of fermented beverages. The determination of aromatic compounds requires global non-targeted profiling of the volatile organic compounds (VOCs) in the beverages. However, experimental VOC profiling result depends on the chosen VOC collection method. Objectives This study aims to observe the impact of using different sample preparation techniques [dynamic headspace (DHS), vortex-assisted liquid–liquid microextraction (VALLME), multiple stir bar sorptive extraction (mSBSE), solid phase extraction (SPE), and solid phase micro-extraction (SPME)] to figure out the most suitable sample preparation protocol for profiling the VOCs from fermented beverages. Methods Five common sample preparation methods were studied with beer, cider, red wine, and white wine samples. After the sample preparation, collected VOCs were analyzed by two-dimensional gas chromatography coupled with time of flight mass spectrometry (GCxGC-TOFMS). Results GCxGC oven parameters can be optimized with the Box–Behnken surface response model and response measure on peak dispersion. Due to the unavoidable column and detector saturation during metabolomic analysis, errors may happen during mass spectrum construction. Profiling results obtained with different sample preparation methods show considerable variance. Common findings occupy a small fraction of total annotated VOCs. For known fermentative aromas, best coverage can be reached by using SPME together with SPE for beer, and VALLME for wine and cider. Conclusions GCxGC-TOFMS is a promising tool for non-targeted profiling on VOCs from fermented beverages. However, a proper data processing protocol is lacking for metabolomic analysis. Each sample preparation method has a specific profiling spectrum on VOC profiling. The coverage of the VOC metabolome can be improved by combining complementary methods.

A modular framework for the development of targeted Covid-19 blood transcript profiling panels

Background: Covid-19 morbidity and mortality are associated with a dysregulated immune response. Tools are needed to enhance existing immune profiling capabilities in affected patients. Here we aimed to develop an approach to support the design of focused blood transcriptome panels for profiling the immune response to SARS-CoV-2 infection. Methods: We designed a pool of candidates based on a pre-existing and well-characterized repertoire of blood transcriptional modules. Available Covid-19 blood transcriptome data was also used to guide this process. Further selection steps relied on expert curation. Additionally, we developed several custom web applications to support the evaluation of candidates. Results: As a proof of principle, we designed three targeted blood transcript panels, each with a different translational connotation: immunological relevance, therapeutic development relevance and SARS biology relevance. Conclusion: Altogether the work presented here may contribute to the future expansion of immune profiling capabilities via targeted profiling of blood transcript abundance in Covid-19 patients.