COSMIC: the Catalogue Of Somatic Mutations In Cancer.

COSMIC, the Catalogue Of Somatic Mutations In Cancer (https://cancer.sanger.ac.uk) is the most detailed and comprehensive resource for exploring the effect of somatic mutations in human cancer. The latest release, COSMIC v86 (August 2018), includes almost 6 million coding mutations across 1.4 million tumour samples, curated from over 26 000 publications. In addition to coding mutations, COSMIC covers all the genetic mechanisms by which somatic mutations promote cancer, including non-coding mutations, gene fusions, copy-number variants and drug-resistance mutations. COSMIC is primarily hand-curated, ensuring quality, accuracy and descriptive data capture. Building on our manual curation processes, we are introducing new initiatives that allow us to prioritize key genes and diseases, and to react more quickly and comprehensively to new findings in the literature. Alongside improvements to the public website and data-download systems, new functionality in COSMIC-3D allows exploration of mutations within three-dimensional protein structures, their protein structural and functional impacts, and implications for druggability. In parallel with COSMIC's deep and broad variant coverage, the Cancer Gene Census (CGC) describes a curated catalogue of genes driving every form of human cancer. Currently describing 719 genes, the CGC has recently introduced functional descriptions of how each gene drives disease, summarized into the 10 cancer Hallmarks.

Programming Light-Harvesting Efficiency Using DNA Origami.

The remarkable performance and quantum efficiency of biological light-harvesting complexes has prompted a multidisciplinary interest in engineering biologically inspired antenna systems as a possible route to novel solar cell technologies. Key to the effectiveness of biological "nanomachines" in light capture and energy transport is their highly ordered nanoscale architecture of photoactive molecules. Recently, DNA origami has emerged as a powerful tool for organizing multiple chromophores with base-pair accuracy and full geometric freedom. Here, we present a programmable antenna array on a DNA origami platform that enables the implementation of rationally designed antenna structures. We systematically analyze the light-harvesting efficiency with respect to number of donors and interdye distances of a ring-like antenna using ensemble and single-molecule fluorescence spectroscopy and detailed Förster modeling. This comprehensive study demonstrates exquisite and reliable structural control over multichromophoric geometries and points to DNA origami as highly versatile platform for testing design concepts in artificial light-harvesting networks.

Learning exact enumeration and approximate estimation in deep neural network models.

A system for approximate number discrimination has been shown to arise in at least two types of hierarchical neural network models-a generative Deep Belief Network (DBN) and a Hierarchical Convolutional Neural Network (HCNN) trained to classify natural objects. Here, we investigate whether the same two network architectures can learn to recognise exact numerosity. A clear difference in performance could be traced to the specificity of the unit responses that emerged in the last hidden layer of each network. In the DBN, the emergence of a layer of monotonic 'summation units' was sufficient to produce classification behaviour consistent with the behavioural signature of the approximate number system. In the HCNN, a layer of units uniquely tuned to the transition between particular numerosities effectively encoded a thermometer-like 'numerosity code' that ensured near-perfect classification accuracy. The results support the notion that parallel pattern-recognition mechanisms may give rise to exact and approximate number concepts, both of which may contribute to the learning of symbolic numbers and arithmetic.

Instabilities and solitons in systems with spatiotemporal dispersion.

A simple model based on the 1D nonlinear Schrödinger equation is studied, which contains both spatially and temporally dispersive terms. Parametric instabilities for plane waves are analyzed in detail, and solitary waves (both bright and dark) are found. The model presented here is able to describe the non-trivial unstable dynamics of intense, nonlinear light propagation near a material resonance in presence of negative spatial dispersion. We provide as a practical example the light propagation near the tail of an exciton-polariton resonance in a specially designed semiconductor superlattice.

Studying light-harvesting models with superconducting circuits.

The process of photosynthesis, the main source of energy in the living world, converts sunlight into chemical energy. The high efficiency of this process is believed to be enabled by an interplay between the quantum nature of molecular structures in photosynthetic complexes and their interaction with the environment. Investigating these effects in biological samples is challenging due to their complex and disordered structure. Here we experimentally demonstrate a technique for studying photosynthetic models based on superconducting quantum circuits, which complements existing experimental, theoretical, and computational approaches. We demonstrate a high degree of freedom in design and experimental control of our approach based on a simplified three-site model of a pigment protein complex with realistic parameters scaled down in energy by a factor of 105. We show that the excitation transport between quantum-coherent sites disordered in energy can be enabled through the interaction with environmental noise. We also show that the efficiency of the process is maximized for structured noise resembling intramolecular phononic environments found in photosynthetic complexes.

Publisher Correction: Studying light-harvesting models with superconducting circuits.

The original HTML version of this Article contained an error in the second mathematical expression in the fourth sentence of the fourth paragraph of the 'Excitation transfer with uniform white noise' section of the Results. This has been corrected in the HTML version of the Article.The original PDF version of this Article incorrectly stated that 'Correspondence and requests for materials should be addressed to A. Pcn.', instead of the correct 'Correspondence and requests for materials should be addressed to A. Potocnik'. This has been corrected in the PDF version of the Article.