Expression Atlas update: insights from sequencing data at both bulk and single cell level.

Expression Atlas (www.ebi.ac.uk/gxa) and its newest counterpart the Single Cell Expression Atlas (www.ebi.ac.uk/gxa/sc) are EMBL-EBI's knowledgebases for gene and protein expression and localisation in bulk and at single cell level. These resources aim to allow users to investigate their expression in normal tissue (baseline) or in response to perturbations such as disease or changes to genotype (differential) across multiple species. Users are invited to search for genes or metadata terms across species or biological conditions in a standardised consistent interface. Alongside these data, new features in Single Cell Expression Atlas allow users to query metadata through our new cell type wheel search. At the experiment level data can be explored through two types of dimensionality reduction plots, t-distributed Stochastic Neighbor Embedding (tSNE) and Uniform Manifold Approximation and Projection (UMAP), overlaid with either clustering or metadata information to assist users' understanding. Data are also visualised as marker gene heatmaps identifying genes that help confer cluster identity. For some data, additional visualisations are available as interactive cell level anatomograms and cell type gene expression heatmaps.

Immunohistochemical evaluation of superficial and invasive front of oral squamous cell carcinoma using epithelial membrane antigen as a marker.

Background: Epithelial membrane antigen (EMA) has been used as a marker for the expression of tumour margins in various glandular neoplastic lesions. Histopathologically, oral squamous cell carcinoma (OSCC) may exhibit several features within the same tumour cells, portraying that these cells at the invasive margins commonly display certain features that differ from those of the superficial part of the tumour. Aim: To identify and study the invasive tumour front and also to recognise any micrometastases in an OSCC lesion. Materials and Method: A retrospective study of 30 OSCC cases with superficial and most invasive parts were sectioned at 4 µm. Routine H&E staining and immunohistochemical staining with mouse antihuman EMA were done. The OSCC cases were graded into well differentiated squamous cell carcinoma (WDSCC), moderately differentiated squamous cell carcinoma (MDSCC) and poorly differentiated squamous cell carcinoma (PDSCC). The EMA-stained slides were observed and analysed under higher magnification to identify the individual EMA-stained cells. Results: Analysis of Variance (ANOVA) analysis revealed that when comparing the superficial and invasive fronts of OSCC, it was evident that the P values were significant across the groups. In WDSCC, positive predictive value was 70.6% and sensitivity was 100% when the same slide was analysed for large and small islands to individual cells in an EMA-stained section, while MDSCC and PDSCC showed both sensitivity and positive predictive value to be 100%. Conclusion: EMA could be considered a useful prognostic marker for describing the nature of the neoplastic epithelium as well as recognising the typical anaplastic cells in cases of OSCC.

Analysis of folate and curcumin-conjugated cadmium sulfide cystein quantum dots for targeted cancer therapy.

The aim of this study was to develop the ranostic nanocomposite by conjugating quantum dots with functional, therapeutic and targeting moieties. The quantum dots nanoparticles were used to diagnose and deliver anti-tumor drugs in a controlled manner to cancerous cells by fusing with tumor cell surfaces. To enhance the attachment of the nano-composite to specific tumor cells without harming neighboring normal cells, folic acid was conjugated with the nano-composite as folate receptors are over expressed in different kinds of tumors. The study was conducted for one year at the University of Punjab. The quantum dots were synthesized by a hydrothermal process using cadmium acetate and sodium sulfide. The response was evaluated on breast tumor samples for binding and nano-composite delivery under a fluorescent microscope. Fourier-transform infrared analysis was performed to confirm CdS conjugation with cysteine, folic acid and curcumin. The results showed that the quantum dot conjugate provides a two-way attack on cancer cells and causes increased cellular apoptosis. Further testing on murine animal models is required to confirm the results of this research study.

Evaluation of Electrosurgery and Diode Laser in Gingival Depigmentation.

Introduction: Gingival depigmentation is a surgical procedure done to eliminate or reduce gingival hyperpigmentation. Various techniques are employed such as scalpel de-epithelization, gingivectomy, electrosurgery, use of chemical agents, cryosurgery, and lasers. The present study was conducted to assess the efficacy of laser and electrosurgical procedure in reducing gingival pigmentation in terms of pain, wound healing, and recurrence of melanin pigmentation. Methodology: A prospective study was conducted on 40 subjects affected by melanin pigmentation. Group I patients were treated with electrosurgery and Group II patients with diode laser procedure. Evaluation for pain was done intraoperatively, 24 hours and 7 days using VAS. Wound healing and recurrence of pigmentation was assessed at one month and three months. Results: No significant difference was noted between the two groups for pain assessment at 7 days with P > 0.001. Both electrosurgery and laser group showed significant differences between intraoperative time period to 24 hours and 24 hours to 7 days at P < 0.001 for pain. Conclusion: Esthetic demands necessitate cosmetic gingival depigmentation procedure. Laser diode photoablation proves to be an effective and reliable technique in achieving the same.

Expression Atlas update: gene and protein expression in multiple species.

The EMBL-EBI Expression Atlas is an added value knowledge base that enables researchers to answer the question of where (tissue, organism part, developmental stage, cell type) and under which conditions (disease, treatment, gender, etc) a gene or protein of interest is expressed. Expression Atlas brings together data from >4500 expression studies from >65 different species, across different conditions and tissues. It makes these data freely available in an easy to visualise form, after expert curation to accurately represent the intended experimental design, re-analysed via standardised pipelines that rely on open-source community developed tools. Each study's metadata are annotated using ontologies. The data are re-analyzed with the aim of reproducing the original conclusions of the underlying experiments. Expression Atlas is currently divided into Bulk Expression Atlas and Single Cell Expression Atlas. Expression Atlas contains data from differential studies (microarray and bulk RNA-Seq) and baseline studies (bulk RNA-Seq and proteomics), whereas Single Cell Expression Atlas is currently dedicated to Single Cell RNA-Sequencing (scRNA-Seq) studies. The resource has been in continuous development since 2009 and it is available at https://www.ebi.ac.uk/gxa.

From ArrayExpress to BioStudies.

ArrayExpress (https://www.ebi.ac.uk/arrayexpress) is an archive of functional genomics data at EMBL-EBI, established in 2002, initially as an archive for publication-related microarray data and was later extended to accept sequencing-based data. Over the last decade an increasing share of biological experiments involve multiple technologies assaying different biological modalities, such as epigenetics, and RNA and protein expression, and thus the BioStudies database (https://www.ebi.ac.uk/biostudies) was established to deal with such multimodal data. Its central concept is a study, which typically is associated with a publication. BioStudies stores metadata describing the study, provides links to the relevant databases, such as European Nucleotide Archive (ENA), as well as hosts the types of data for which specialized databases do not exist. With BioStudies now fully functional, we are able to further harmonize the archival data infrastructure at EMBL-EBI, and ArrayExpress is being migrated to BioStudies. In future, all functional genomics data will be archived at BioStudies. The process will be seamless for the users, who will continue to submit data using the online tool Annotare and will be able to query and download data largely in the same manner as before. Nevertheless, some technical aspects, particularly programmatic access, will change. This update guides the users through these changes.

Expression Atlas update: from tissues to single cells.

Expression Atlas is EMBL-EBI's resource for gene and protein expression. It sources and compiles data on the abundance and localisation of RNA and proteins in various biological systems and contexts and provides open access to this data for the research community. With the increased availability of single cell RNA-Seq datasets in the public archives, we have now extended Expression Atlas with a new added-value service to display gene expression in single cells. Single Cell Expression Atlas was launched in 2018 and currently includes 123 single cell RNA-Seq studies from 12 species. The website can be searched by genes within or across species to reveal experiments, tissues and cell types where this gene is expressed or under which conditions it is a marker gene. Within each study, cells can be visualized using a pre-calculated t-SNE plot and can be coloured by different features or by cell clusters based on gene expression. Within each experiment, there are links to downloadable files, such as RNA quantification matrices, clustering results, reports on protocols and associated metadata, such as assigned cell types.

ArrayExpress update - from bulk to single-cell expression data.

ArrayExpress (https://www.ebi.ac.uk/arrayexpress) is an archive of functional genomics data from a variety of technologies assaying functional modalities of a genome, such as gene expression or promoter occupancy. The number of experiments based on sequencing technologies, in particular RNA-seq experiments, has been increasing over the last few years and submissions of sequencing data have overtaken microarray experiments in the last 12 months. Additionally, there is a significant increase in experiments investigating single cells, rather than bulk samples, known as single-cell RNA-seq. To accommodate these trends, we have substantially changed our submission tool Annotare which, along with raw and processed data, collects all metadata necessary to interpret these experiments. Selected datasets are re-processed and loaded into our sister resource, the value-added Expression Atlas (and its component Single Cell Expression Atlas), which not only enables users to interpret the data easily but also serves as a test for data quality. With an increasing number of studies that combine different assay modalities (multi-omics experiments), a new more general archival resource the BioStudies Database has been developed, which will eventually supersede ArrayExpress. Data submissions will continue unchanged; all existing ArrayExpress data will be incorporated into BioStudies and the existing accession numbers and application programming interfaces will be maintained.

Gramene 2018: unifying comparative genomics and pathway resources for plant research.

Gramene (http://www.gramene.org) is a knowledgebase for comparative functional analysis in major crops and model plant species. The current release, #54, includes over 1.7 million genes from 44 reference genomes, most of which were organized into 62,367 gene families through orthologous and paralogous gene classification, whole-genome alignments, and synteny. Additional gene annotations include ontology-based protein structure and function; genetic, epigenetic, and phenotypic diversity; and pathway associations. Gramene's Plant Reactome provides a knowledgebase of cellular-level plant pathway networks. Specifically, it uses curated rice reference pathways to derive pathway projections for an additional 66 species based on gene orthology, and facilitates display of gene expression, gene-gene interactions, and user-defined omics data in the context of these pathways. As a community portal, Gramene integrates best-of-class software and infrastructure components including the Ensembl genome browser, Reactome pathway browser, and Expression Atlas widgets, and undergoes periodic data and software upgrades. Via powerful, intuitive search interfaces, users can easily query across various portals and interactively analyze search results by clicking on diverse features such as genomic context, highly augmented gene trees, gene expression anatomograms, associated pathways, and external informatics resources. All data in Gramene are accessible through both visual and programmatic interfaces.