Spatial Transcriptomics: Constructing a Single-Cell Resolution Transcriptome-Wide Expression Atlas.

The method described here aims at the construction of a single-cell resolution gene expression atlas for an animal or tissue, combining in situ hybridization (ISH) and single-cell mRNA-sequencing (scRNAseq).A high resolution and medium-coverage gene expression atlas of an animal or tissue of interest can be obtained by performing a series of ISH experiments, followed by a process of image registration and gene expression averaging. Using the overlapping fraction of the genes, concomitantly obtained scRNAseq data can be fitted into the spatial context of the gene expression atlas, complementing the coverage by genes.

The systems biology format converter.

BACKGROUND: Interoperability between formats is a recurring problem in systems biology research. Many tools have been developed to convert computational models from one format to another. However, they have been developed independently, resulting in redundancy of efforts and lack of synergy. RESULTS: Here we present the System Biology Format Converter (SBFC), which provide a generic framework to potentially convert any format into another. The framework currently includes several converters translating between the following formats: SBML, BioPAX, SBGN-ML, Matlab, Octave, XPP, GPML, Dot, MDL and APM. This software is written in Java and can be used as a standalone executable or web service. CONCLUSIONS: The SBFC framework is an evolving software project. Existing converters can be used and improved, and new converters can be easily added, making SBFC useful to both modellers and developers. The source code and documentation of the framework are freely available from the project web site.

High-throughput spatial mapping of single-cell RNA-seq data to tissue of origin.

Understanding cell type identity in a multicellular organism requires the integration of gene expression profiles from individual cells with their spatial location in a particular tissue. Current technologies allow whole-transcriptome sequencing of spatially identified cells but lack the throughput needed to characterize complex tissues. Here we present a high-throughput method to identify the spatial origin of cells assayed by single-cell RNA-sequencing within a tissue of interest. Our approach is based on comparing complete, specificity-weighted mRNA profiles of a cell with positional gene expression profiles derived from a gene expression atlas. We show that this method allocates cells to precise locations in the brain of the marine annelid Platynereis dumerilii with a success rate of 81%. Our method is applicable to any system that has a reference gene expression database of sufficiently high resolution.

BioModels: ten-year anniversary.

BioModels (http://www.ebi.ac.uk/biomodels/) is a repository of mathematical models of biological processes. A large set of models is curated to verify both correspondence to the biological process that the model seeks to represent, and reproducibility of the simulation results as described in the corresponding peer-reviewed publication. Many models submitted to the database are annotated, cross-referencing its components to external resources such as database records, and terms from controlled vocabularies and ontologies. BioModels comprises two main branches: one is composed of models derived from literature, while the second is generated through automated processes. BioModels currently hosts over 1200 models derived directly from the literature, as well as in excess of 140,000 models automatically generated from pathway resources. This represents an approximate 60-fold growth for literature-based model numbers alone, since BioModels' first release a decade ago. This article describes updates to the resource over this period, which include changes to the user interface, the annotation profiles of models in the curation pipeline, major infrastructure changes, ability to perform online simulations and the availability of model content in Linked Data form. We also outline planned improvements to cope with a diverse array of new challenges.

Identifying cell types from spatially referenced single-cell expression datasets.

Complex tissues, such as the brain, are composed of multiple different cell types, each of which have distinct and important roles, for example in neural function. Moreover, it has recently been appreciated that the cells that make up these sub-cell types themselves harbour significant cell-to-cell heterogeneity, in particular at the level of gene expression. The ability to study this heterogeneity has been revolutionised by advances in experimental technology, such as Wholemount in Situ Hybridizations (WiSH) and single-cell RNA-sequencing. Consequently, it is now possible to study gene expression levels in thousands of cells from the same tissue type. After generating such data one of the key goals is to cluster the cells into groups that correspond to both known and putatively novel cell types. Whilst many clustering algorithms exist, they are typically unable to incorporate information about the spatial dependence between cells within the tissue under study. When such information exists it provides important insights that should be directly included in the clustering scheme. To this end we have developed a clustering method that uses a Hidden Markov Random Field (HMRF) model to exploit both quantitative measures of expression and spatial information. To accurately reflect the underlying biology, we extend current HMRF approaches by allowing the degree of spatial coherency to differ between clusters. We demonstrate the utility of our method using simulated data before applying it to cluster single cell gene expression data generated by applying WiSH to study expression patterns in the brain of the marine annelid Platynereis dumereilii. Our approach allows known cell types to be identified as well as revealing new, previously unexplored cell types within the brain of this important model system.

bioWeb3D: an online webGL 3D data visualisation tool.

BACKGROUND: Data visualization is critical for interpreting biological data. However, in practice it can prove to be a bottleneck for non trained researchers; this is especially true for three dimensional (3D) data representation. Whilst existing software can provide all necessary functionalities to represent and manipulate biological 3D datasets, very few are easily accessible (browser based), cross platform and accessible to non-expert users. RESULTS: An online HTML5/WebGL based 3D visualisation tool has been developed to allow biologists to quickly and easily view interactive and customizable three dimensional representations of their data along with multiple layers of information. Using the WebGL library Three.js written in Javascript, bioWeb3D allows the simultaneous visualisation of multiple large datasets inputted via a simple JSON, XML or CSV file, which can be read and analysed locally thanks to HTML5 capabilities. CONCLUSIONS: Using basic 3D representation techniques in a technologically innovative context, we provide a program that is not intended to compete with professional 3D representation software, but that instead enables a quick and intuitive representation of reasonably large 3D datasets.