RESUMO
To better understand how tumours develop, identify prognostic biomarkers and find new treatments, researchers have generated vast catalogues of cancer genome data. However, these datasets are complex, so interpreting their important features requires specialized computational skills and analytical tools, which presents a significant technical challenge. To address this, we developed CRUX, a platform for exploring genomic data from cancer cohorts. CRUX enables researchers to perform common analyses including cohort comparisons, biomarker discovery, survival analysis, and to create visualisations including oncoplots and lollipop charts. CRUX simplifies cancer genome analysis in several ways: (i) it has an easy-to-use graphical interface; (ii) it enables users to create custom cohorts, as well as analyse precompiled public and private user-created datasets; (iii) it allows analyses to be run locally to address data privacy concerns (though an online version is also available) and (iv) it makes it easy to use additional specialized tools by exporting data in the correct formats. We showcase CRUX's capabilities with case studies employing different types of cancer genome analysis, demonstrating how it can be used flexibly to generate valuable insights into cancer biology. CRUX is freely available at https://github.com/CCICB/CRUX and https://ccicb.shinyapps.io/crux (DOI: 10.5281/zenodo.8015714).
RESUMO
The fungus Aspergillus fumigatus, the cause of invasive aspergillosis (IA), is a serious risk to transplant patients and those with respiratory diseases. Host immune suppression is considered the most important factor for the development of IA. Less is known about the importance of fungal virulence in the development of IA including the significance of variation between isolates. In this study, isolates of A. fumigatus from cases diagnosed as having proven IA or colonisation (no evidence of IA) were compared in assays to measure isolate virulence. These assays included the measurement of radial growth and protease production on agar, sensitivity to UV light and oxidative stressors, and virulence in Tenebrio molitor (mealworm) larvae. These assays did not reveal obvious differences in virulence between the two groups of isolates; this provided the impetus to conduct genomic analysis. Whole genome sequencing and analysis did not allow grouping into coloniser or IA isolates. However, focused analysis of single nucleotide polymorphisms revealed variation in three putative genes: AFUA_5G09420 (ccg-8), AFUA_4G00330, and AFUA_4G00350. These are known to be responsive to azole exposure, and ccg-8 deletion leads to azole hypersensitivity in other fungi. A. fumigatus virulence is challenging, but the findings of this study indicate that further research into the response to oxidative stress and azole exposure are required to understand the development of IA.
