59 research outputs found
A Bayesian method to cluster single-cell RNA sequencing data using Copy Number Alterations
No full textAbstract
Motivation
Cancers are composed by several heterogeneous subpopulations, each one harbouring different genetic and epigenetic somatic alterations that contribute to disease onset and therapy response. In recent years, copy number alterations leading to tumour aneuploidy have been identified as potential key drivers of such populations, but the definition of the precise makeup of cancer subclones from sequencing assays remains challenging. In the end, little is known about the mapping between complex copy number alterations and their effect on cancer phenotypes.
Results
We introduce CONGAS, a Bayesian probabilistic method to phase bulk DNA and single-cell RNA measurements from independent assays. CONGAS jointly identifies clusters of single cells with subclonal copy number alterations, and differences in RNA expression. The model builds statistical priors leveraging bulk DNA sequencing data, does not require a normal reference and scales fast thanks to a GPU backend and variational inference. We test CONGAS on both simulated and real data, and find that it can determine the tumour subclonal composition at the single-cell level together with clone-specific RNA phenotypes in tumour data generated from both 10x and Smart-Seq assays.
Availability
CONGAS is available as 2 packages: CONGAS (https://github.com/caravagnalab/congas), which implements the model in Python, and RCONGAS (https://caravagnalab.github.io/rcongas/), which provides R functions to process inputs, outputs, and run CONGAS fits. The analysis of real data and scripts to generate figures of this paper are available via RCONGAS; code associated to simulations is available at https://github.com/caravagnalab/rcongas_test
Mean and Outcomes
No full textThe article explores the role of research in architecture as an intermediate territory between science and art, emphasising the importance of expressive tools such as drawing, writing and typological comparison. Through the concept of ‘archaeology of the design process’, the author reflects on how method, subjectivity and context are indispensable elements in producing results that are original yet open to discussion. Architectural research is seen as a dynamic process, in which the comparison with existing cases and the conscious use of representative tools allow the construction of sharable knowledge that is never definitive
EDOTENSIOMETRO DA LABORATORIO
No full textA model of combined oedometer and tensiometer for laboratory examination of the behaviour of rebuilded samples of swelling soils is presented. It allows registration of simultaneous variation of mechanical stress (overburden potential) and water potential (poral water pressure or interstitial water pressure). The measurement of the uptake as well as the release of water from the sample are obtained through continuous weight determinations of the water content in a beacker tank. Issues from any eventual air release in the hydraulic system (through air trap) and loss by evaporation both at the beaker tank and from the upper side of the soil sample are faced and discussed
Heme Oxigenase-1 (HO-1) and Oxidative Stress in Rat Heart
No full textLow oxygen tension (hypoxia) is a potent regulator of diverse biological processes. Mammalian cells respond to hypoxia in part by increased expression of several genes that encode for tissue-specific and ubiquitous proteins. The aim of this study was to evaluate the effects of chronic exposure to low tension of oxygen (hypoxia) on the induction of heme-oxygenase-1 (HO-1) as an oxidative stress model. Adult male Wistar rats were used and subdivided randomly in two groups: A:(n=10) maintained in normoxic conditions and B: (n=10) maintained in hypoxic conditions. The animal of both groups were sacrificed after 14 days. Group A showed an evident non-specific reaction. Group B presented an increased positively of HO-1 immunoreaction. This data was confirmed by western blot analysis of protein and by the study of mRNA through rtPCR. These results suggest that myocardial adaptive response to hypoxia involves up-regulation of HO-1 in cardiac cells, indicating that this enzyme may participate in regulating vascular tone via CO and thereby contributing to the pathophysiologically important defense mechanism of the heart
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