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.

Numerous studies have determined that physical cues, especially the nanotopography of materials, play key roles in directing stem cell differentiation. However, most research on nanoarrays for stem cell fate regulation is based on nonbiodegradable materials, such as silicon wafers, TiO, and poly(methyl methacrylate), which are rarely used as tissue engineering biomaterials. In this study, we prepared biodegradable polylactic acid (PLA) nanopillar arrays with different diameters but the same center-to-center distance using a series of anodic aluminum oxide nanowell arrays as templates. Human adipose-derived stem cells (hADSCs) were selected to investigate the effect of the diameter of PLA nanopillar arrays on stem cell differentiation. By culturing hADSCs without the assistance of any growth factors or osteogenic-induced media, the differentiation tendencies of hADSCs on the nanopillar arrays were assessed at the gene and protein levels. The assessment results suggested that the osteogenic differentiation of hADSCs can be driven by nanopillar arrays, especially by nanopillar arrays with a diameter of 200 nm. Moreover, an in vivo animal model of the samples demonstrated that PLA film with the 200 nm pillar array exhibits an improved ectopic osteogenic ability compared with the planar PLA film after 4 weeks of ectopic implantation. This study has provided a new variable to investigate in the interaction between stem cells and nanoarray structures, which will guide the bone regeneration clinical research field. This work paves the way for the utility of degradable biopolymer nanoarrays with specific geometrical and mechanical signals in biomedical applications, such as patches and strips for spine fusion, bone crack repair, and restoration of tooth enamel.

Localized surface plasmon resonance-based plasmonic biosensors are interesting candidates for the design of portable optical biosensor platforms owing to their integration, miniaturization, multiparameter, real-time, and label-free detection characteristics. Plasmonic biosensor arrays that have been combined with microfluidics have been developed herein to detect exosomes label-free. Gold nano-ellipsoid arrays were fabricated with low-cost anodic aluminum oxide thin films that act as shadow masks for evaporation of Au. The nano-ellipsoid arrays were integrated with a microfluidic chip to achieve multiparameter detection. The anti-CD63 antibody that is specific to the exosome transmembrane protein CD63 is modified on the surface of the nano-ellipsoids. Exosome samples were injected into the biosensor platform at different concentrations and detected successfully. The detection limit was 1 ng/mL. The proposed plasmonic biosensor array can be universally applicable for the detection of other biomarkers by simply changing the antibody on the surface of the Au nano-ellipsoids. Moreover, this biosensor platform is envisaged to be potentially useful in the development of low-cost plasmonic-based biosensors for biomarker detection and for the investigation of exosomes for noninvasive disease diagnoses.

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It is well-accepted that most osteogenic differentiation processes do need growth factors assistance to improve efficiency. As a material cue, hydroxyapatite (HAp) can promote osteogenic differentiation of stem cells only in a way. Up to now, rare work related to the relationship between HAp nanostructures and stem cells in osteogenic differentiation process without the assistance of growth factors has been reported. In this study, one-dimensional (1D) HAp nanostructures with tunable length were synthesized by an oleic acid assisted solvothermal method by adjusting the alcohol/water ratio (η). The morphology of 1D HAp nanostructures can be changed from long nanowires into nanorods with the η value change. Different substrates constructed by 1D HAp nanostructures were prepared to investigate the effect of morphology of nanostructured HAp on stem cell fate without any growth factors or differentiation induce media. Human adipose-derived stem cells (hADSCs), a kind of promising stem cell for autologous stem cell tissue engineering, were used as the stem cell model. The experiments prove that HAp morphology can determine the performance of hADSCs cultured on different substrates. Substrate constructed by HAp nanorods (100 nm) is of little benefit to osteogenic differentiations. Substrate constructed on HAp long nanowires (50 μm) causes growth and spread inhibition of hADSCs, which even causes most cells death after 7 days of culture. However, substrate constructed by HAp short nanowires (5 μm) can destine the hADSCs differentiation to osteoblasts efficiently in normal medium (after 3 weeks) without any growth factors. It is surprise that hADSCs have changed to polyhedral morphology and exhibited the tendency to osteogenic differentiation after only 24 h culture. Hydroxyapatite nanostructures mediated stem cell osteogenic differentiation excluding growth factors provides a powerful cue to design biomaterials with special nanostructures, and helps to elucidate the interaction of stem cell and biomaterials nanostructures. The results from this study are promising for application in bone tissue engineering.

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BackgroundHigh-throughput transcriptomic data generated by microarray experiments is the most abundant and frequently stored kind of data currently used in translational medicine studies. Although microarray data is supported in data warehouses such as tranSMART, when querying relational databases for hundreds of different patient gene expression records queries are slow due to poor performance. Non-relational data models, such as the key-value model implemented in NoSQL databases, hold promise to be more performant solutions. Our motivation is to improve the performance of the tranSMART data warehouse with a view to supporting Next Generation Sequencing data.ResultsIn this paper we introduce a new data model better suited for high-dimensional data storage and querying, optimized for database scalability and performance. We have designed a key-value pair data model to support faster queries over large-scale microarray data and implemented the model using HBase, an implementation of Google's BigTable storage system. An experimental performance comparison was carried out against the traditional relational data model implemented in both MySQL Cluster and MongoDB, using a large publicly available transcriptomic data set taken from NCBI GEO concerning Multiple Myeloma. Our new key-value data model implemented on HBase exhibits an average 5.24-fold increase in high-dimensional biological data query performance compared to the relational model implemented on MySQL Cluster, and an average 6.47-fold increase on query performance on MongoDB.ConclusionsThe performance evaluation found that the new key-value data model, in particular its implementation in HBase, outperforms the relational model currently implemented in tranSMART. We propose that NoSQL technology holds great promise for large-scale data management, in particular for high-dimensional biological data such as that demonstrated in the performance evaluation described in this paper. We aim to use this new data model as a basis for migrating tranSMART's implementation to a more scalable solution for Big Data.

Carbon quantum dots (CQDs) are a new type of fluorescent nanoparticle for cell imaging and tracking. However, they would easily diffuse and quench, followed by the loss of their fluorescence ability. By connecting their functional groups with other nanoparticles, the CQDs will be protected from destruction and exhibit long-time fluorescence. Here, carbon quantum dot-hydroxyapatite (CQD-HAp) hybrid nanorods were prepared by the self-assembly of CQDs on the surface of HAp nanorods through a facile one-pot process. The morphology and size of the CQD-HAp hybrid nanorods can be well controlled by using oleic acid, which meanwhile is the source of CQDs. The hydrophilic CQD-HAp hybrid nanorods have prolonged fluorescence life due to the connection between CQDs and HAp nanorods, and exhibit a higher fluorescence quantum yield than pure CQDs. In addition, when hybrid nanorods load doxorubicin (Dox) to form Dox-CQD-HAp hybrid nanorods, they can more efficiently kill human cervical cancer (HeLa) cells, rather than human prostatic cancer (PC-3) cells. Long time fluorescence for cell imaging and high efficiency in killing cancer cells as a drug-delivery medium make CQD-HAp hybrid nanorods have great potential applications in the bio-field.