Raman-based machine learning platform reveals unique metabolic differences between IDHmut and IDHwt glioma.

BACKGROUND: Formalin-fixed, paraffin-embedded (FFPE) tissue slides are routinely used in cancer diagnosis, clinical decision-making, and stored in biobanks, but their utilization in Raman spectroscopy-based studies has been limited due to the background coming from embedding media. METHODS: Spontaneous Raman spectroscopy was used for molecular fingerprinting of FFPE tissue from 46 patient samples with known methylation subtypes. Spectra were used to construct tumor/non-tumor, IDH1WT/IDH1mut, and methylation-subtype classifiers. Support vector machine and random forest were used to identify the most discriminatory Raman frequencies. Stimulated Raman spectroscopy was used to validate the frequencies identified. Mass spectrometry of glioma cell lines and TCGA were used to validate the biological findings. RESULTS: Here we develop APOLLO (rAman-based PathOLogy of maLignant glioma) - a computational workflow that predicts different subtypes of glioma from spontaneous Raman spectra of FFPE tissue slides. Our novel APOLLO platform distinguishes tumors from nontumor tissue and identifies novel Raman peaks corresponding to DNA and proteins that are more intense in the tumor. APOLLO differentiates isocitrate dehydrogenase 1 mutant (IDH1mut) from wildtype (IDH1WT) tumors and identifies cholesterol ester levels to be highly abundant in IDHmut glioma. Moreover, APOLLO achieves high discriminative power between finer, clinically relevant glioma methylation subtypes, distinguishing between the CpG island hypermethylated phenotype (G-CIMP)-high and G-CIMP-low molecular phenotypes within the IDH1mut types. CONCLUSIONS: Our results demonstrate the potential of label-free Raman spectroscopy to classify glioma subtypes from FFPE slides and to extract meaningful biological information thus opening the door for future applications on these archived tissues in other cancers.

Network analytics for drug repurposing in COVID-19.

To better understand the potential of drug repurposing in COVID-19, we analyzed control strategies over essential host factors for SARS-CoV-2 infection. We constructed comprehensive directed protein-protein interaction (PPI) networks integrating the top-ranked host factors, the drug target proteins and directed PPI data. We analyzed the networks to identify drug targets and combinations thereof that offer efficient control over the host factors. We validated our findings against clinical studies data and bioinformatics studies. Our method offers a new insight into the molecular details of the disease and into potentially new therapy targets for it. Our approach for drug repurposing is significant beyond COVID-19 and may be applied also to other diseases.

Simplified and Yet Turing Universal Spiking Neural P Systems with Communication on Request.

Spiking neural P systems are a class of third generation neural networks belonging to the framework of membrane computing. Spiking neural P systems with communication on request (SNQ P systems) are a type of spiking neural P system where the spikes are requested from neighboring neurons. SNQ P systems have previously been proved to be universal (computationally equivalent to Turing machines) when two types of spikes are considered. This paper studies a simplified version of SNQ P systems, i.e. SNQ P systems with one type of spike. It is proved that one type of spike is enough to guarantee the Turing universality of SNQ P systems. Theoretical results are shown in the cases of the SNQ P system used in both generating and accepting modes. Furthermore, the influence of the number of unbounded neurons (the number of spikes in a neuron is not bounded) on the computation power of SNQ P systems with one type of spike is investigated. It is found that SNQ P systems functioning as number generating devices with one type of spike and four unbounded neurons are Turing universal.

Spiking Neural P Systems With Polarizations.

Spiking neural P (SN P) systems are a class of parallel computation models inspired by neurons, where the firing condition of a neuron is described by a regular expression associated with spiking rules. However, it is NP-complete to decide whether the number of spikes is in the length set of the language associated with the regular expression. In this paper, in order to avoid using regular expressions, two major and rather natural modifications in their form and functioning are proposed: the spiking rules no longer check the number of spikes in a neuron, but, in exchange, a polarization is associated with neurons and rules, one of the three electrical charges -, 0,+. Surprisingly enough, the computing devices obtained are still computationally complete, which are able to compute all Turing computable sets of natural numbers. On this basis, the number of neurons in a universal SN P system with polarizations is estimated. Several research directions are mentioned at the end of this paper.

Educating for action: Aligning skills with policies for sustainable development in the Danube river basin.

Sustainable river basin management depends on knowledge, skills and education. The DANCERS project set out to identify feasible options for achieving education for sustainable water management across the Danube river basin, and its integration with broader education and economic development. The study traced the historic, regulatory and educational landscape of water management in the basin, contrasting it with the complex political decision-making, data-heavy decision support, learning-centred collaboration, and information-based participation that are all inherent components of Integrated Water Resource Management (IWRM). While there is a wide range of educational opportunities and mobility schemes available to individuals, there is no coherent network related to training in water management and sustainable development in the study region. Progress in addressing the multi-layered environmental challenges within the basin requires further aligning of economic, environmental and educational policies, advancing the EU Bologna Process across the region, and the development of dedicated training programmes that combine technical and relational skills. The DANCERS project identified key short and medium term needs for education and research to support progressive adoption of sustainable development, and the necessary dialogue across the public and private sectors to align policies. These include the development of new education networks for masters and PhD programmes, including joint programmes; improved access to technical training and life-long learning programmes for skills development; developing formalized and certified competency structures and associated accreditation of institutions where such skilled individuals work; and developing a co-ordinated research infrastructure and pan-basin programme for research for water management and sustainable development.

On the Universality of Axon P Systems.

Axon P systems are computing models with a linear structure in the sense that all nodes (i.e., computing units) are arranged one by one along the axon. Such models have a good biological motivation: an axon in a nervous system is a complex information processor of impulse signals. Because the structure of axon P systems is linear, the computational power of such systems has been proved to be greatly restricted; in particular, axon P systems are not universal as language generators. It remains open whether axon P systems are universal as number generators. In this paper, we prove that axon P systems are universal as both number generators and function computing devices, and investigate the number of nodes needed to construct a universal axon P system. It is proved that four nodes (respectively, nine nodes) are enough for axon P systems to achieve universality as number generators (respectively, function computing devices). These results illustrate that the simple linear structure is enough for axon P systems to achieve a desired computational power.

Small universal spiking neural P systems.

In search for small universal computing devices of various types, we consider here the case of spiking neural P systems (SN P systems), in two variants: as devices that compute functions and as devices that generate sets of numbers. We start with the first case and we produce a universal spiking neural P system with 84 neurons. If a slight generalization of the used rules is adopted, namely, we allow rules for producing simultaneously several spikes, then a considerable reduction, to 49 neurons, is obtained. For SN P systems used as generators of sets of numbers, we find a universal system with restricted rules having 76 neurons and one with extended rules having 50 neurons.