Visualizing omics and clinical data: Which challenges for dealing with their variety?

Life sciences are currently going through a great number of transformations raised by the in-going revolution in high-throughput technologies for the acquisition of data. The integration of their high dimensionality, ranging from omics to clinical data, is becoming one of the most challenging stages. It involves inter-disciplinary developments with the aim to move towards an enhanced understanding of human physiology for caring purposes. Biologists, bioinformaticians, physicians and other experts related to the healthcare domain have to accompany each step of the analysis process in order to investigate and expertise these various data. In this perspective, methods related to information visualization are gaining increasing attention within life sciences. The softwares based on these methods are now well recognized to facilitate expert users' success in carrying out their data analysis tasks. This article aims at reviewing the current methods and techniques dedicated to information visualisation and their current use in software development related to omics or/and clinical data.

rNAV 2.0: a visualization tool for bacterial sRNA-mediated regulatory networks mining.

BACKGROUND: Bacterial sRNA-mediated regulatory networks has been introduced as a powerful way to analyze the fast rewiring capabilities of a bacteria in response to changing environmental conditions. The identification of mRNA targets of bacterial sRNAs is essential to investigate their functional activities. However, this step remains challenging with the lack of knowledge of the topological and biological constraints behind the formation of sRNA-mRNA duplexes. Even with the most sophisticated bioinformatics target prediction tools, the large proportion of false predictions may be prohibitive for further analyses. To deal with this issue, sRNA target analyses can be carried out from the resulting gene lists given by RNA-SEQ experiments when available. However, the number of resulting target candidates may be still huge and cannot be easily interpreted by domain experts who need to confront various biological features to prioritize the target candidates. Therefore, novel strategies have to be carried out to improve the specificity of computational prediction results, before proposing new candidates for an expensive experimental validation stage. RESULT: To address this issue, we propose a new visualization tool rNAV 2.0, for detecting and filtering bacterial sRNA targets for regulatory networks. rNAV is designed to cope with a variety of biological constraints, including the gene annotations, the conserved regions of interaction or specific patterns of regulation. Depending on the application, these constraints can be variously combined to analyze the target candidates, prioritized for instance by a known conserved interaction region, or because of a common function. CONCLUSION: The standalone application implements a set of known algorithms and interaction techniques, and applies them to the new problem of identifying reasonable sRNA target candidates.

Advantages of mixing bioinformatics and visualization approaches for analyzing sRNA-mediated regulatory bacterial networks.

The revolution in high-throughput sequencing technologies has enabled the acquisition of gigabytes of RNA sequences in many different conditions and has highlighted an unexpected number of small RNAs (sRNAs) in bacteria. Ongoing exploitation of these data enables numerous applications for investigating bacterial transacting sRNA-mediated regulation networks. Focusing on sRNAs that regulate mRNA translation in trans, recent works have noted several sRNA-based regulatory pathways that are essential for key cellular processes. Although the number of known bacterial sRNAs is increasing, the experimental validation of their interactions with mRNA targets remains challenging and involves expensive and time-consuming experimental strategies. Hence, bioinformatics is crucial for selecting and prioritizing candidates before designing any experimental work. However, current software for target prediction produces a prohibitive number of candidates because of the lack of biological knowledge regarding the rules governing sRNA-mRNA interactions. Therefore, there is a real need to develop new approaches to help biologists focus on the most promising predicted sRNA-mRNA interactions. In this perspective, this review aims at presenting the advantages of mixing bioinformatics and visualization approaches for analyzing predicted sRNA-mediated regulatory bacterial networks.

Overlap Removal by Stochastic Gradient Descent with(out) Shape Awareness.

In many 2D visualizations, data points are projected without considering their surface area, although they are often represented as shapes in visualization tools. These shapes support the display of information such as labels or encode data with size or color. However, inappropriate shape and size selections can lead to overlaps that obscure information and hinder the visualization's exploration. Overlap Removal (OR) algorithms have been developed as a layout post-processing solution to ensure that the visible graphical elements accurately represent the underlying data. As the original data layout contains vital information about its topology, it is essential for OR algorithms to preserve it as much as possible. This article presents an extension of the previously published FORBID algorithm by introducing a new approach that models OR as a joint stress and scaling optimization problem, utilizing efficient stochastic gradient descent. The goal is to produce an overlap-free layout that proposes a compromise between compactness (to ensure the encoded data is still readable) and preservation of the original layout (to preserve the structures that convey information about the data). Additionally, this article proposes SORDID, a shape-aware adaptation of FORBID that can handle the OR task on data points having any polygonal shape. Our approaches are compared against state-of-the-art algorithms, and several quality metrics demonstrate their effectiveness in removing overlaps while retaining the compactness and structures of the input layouts.

Guaranteed Visibility in Scatterplots with Tolerance.

In 2D visualizations, visibility of every datum's representation is crucial to ease the completion of visual tasks. Such a guarantee is barely respected in complex visualizations, mainly because of overdraws between datum representations that hide parts of the information (e.g., outliers). The literature proposes various Layout Adjustment algorithms to improve the readability of visualizations that suffer from this issue. Manipulating the data in high-dimensional, geometric or visual space; they rely on different strategies with their own strengths and weaknesses. Moreover, most of these algorithms are computationally expensive as they search for an exact solution in the geometric space and do not scale well to large datasets. This article proposes GIST, a layout adjustment algorithm that aims at optimizing three criteria: (i) node visibility guarantee (at least 1 pixel), (ii) node size maximization, and (iii) the original layout preservation. This is achieved by combining a search for the maximum node size that enables to draw all the data points without overlaps, with a limited budget of movements (i.e., limiting the distortions of the original layout). The method's basis relies on the idea that it is not necessary for two data representations to be strictly not overlapping in order to guarantee their visibility in visual space. Our algorithm therefore uses a tolerance in the geometric space to determine the overlaps between pairs of data. The tolerance is optimized such that the approximation computed in the geometric space can lead to visualization without noticeable overdraw after the data rendering rasterization. In addition, such an approximation helps to ease the algorithm's convergence as it reduces the number of constraints to resolve, enabling it to handle large datasets. We demonstrate the effectiveness of our approach by comparing its results to those of state-of-the-art methods on several large datasets.

Toward Efficient Deep Learning for Graph Drawing (DL4GD).

Due to their great performance in many challenges, Deep Learning (DL) techniques keep gaining popularity in many fields. They have been adapted to process graph data structures to solve various complicated tasks such as graph classification and edge prediction. Eventually, they reached the Graph Drawing (GD) task. This paper is an extended version of the previously published (DNN)2 and presents a framework to leverage DL techniques for graph drawing (DL4GD). We demonstrate how it is possible to train a Deep Learning model to extract features from a graph and project them into a graph layout. The method proposes to leverage efficient Convolutional Neural Networks, adapting them to graphs using Graph Convolutions. The graph layout projection is learned by optimizing a cost function that does not require any ground truth layout, as opposed to prior work. This paper also proposes an implementation and benchmark of the framework to study its sensitivity to certain deep learning-related conditions. As the field is novel, and many questions remain to be answered, we do not focus on finding the most optimal implementation of the method, but rather contribute toward a better understanding of the approach potential. More precisely, we study different learning strategies relative to the models training datasets. Finally, we discuss the main advantages and limitations of DL4GD.

Visualizing Food-Drug Interactions in the Thériaque Database.

This paper presents a prototype for the visualization of food-drug interactions implemented in the MIAM project, whose objective is to develop methods for the extraction and representation of these interactions and to make them available in the Thériaque database. The prototype provides users with a graphical visualization showing the hierarchies of drugs and foods in front of each other and the links between them representing the existing interactions as well as additional details about them, including the number of articles reporting the interaction. The prototype is interactive in the following ways: hierarchies can be easily folded and unfolded, a filter can be applied to view only certain types of interactions, and details about a given interaction are displayed when the mouse is moved over the corresponding link. Future work includes proposing a version more suitable for non-health professional users and the representation of the food hierarchy based on a reference classification.

GSAn: an alternative to enrichment analysis for annotating gene sets.

The revolution in new sequencing technologies is greatly leading to new understandings of the relations between genotype and phenotype. To interpret and analyze data that are grouped according to a phenotype of interest, methods based on statistical enrichment became a standard in biology. However, these methods synthesize the biological information by a priori selecting the over-represented terms and may suffer from focusing on the most studied genes that represent a limited coverage of annotated genes within a gene set. Semantic similarity measures have shown great results within the pairwise gene comparison by making advantage of the underlying structure of the Gene Ontology. We developed GSAn, a novel gene set annotation method that uses semantic similarity measures to synthesize a priori Gene Ontology annotation terms. The originality of our approach is to identify the best compromise between the number of retained annotation terms that has to be drastically reduced and the number of related genes that has to be as large as possible. Moreover, GSAn offers interactive visualization facilities dedicated to the multi-scale analysis of gene set annotations. Compared to enrichment analysis tools, GSAn has shown excellent results in terms of maximizing the gene coverage while minimizing the number of terms.

Metabolic network visualization eliminating node redundance and preserving metabolic pathways.

BACKGROUND: The tools that are available to draw and to manipulate the representations of metabolism are usually restricted to metabolic pathways. This limitation becomes problematic when studying processes that span several pathways. The various attempts that have been made to draw genome-scale metabolic networks are confronted with two shortcomings: 1- they do not use contextual information which leads to dense, hard to interpret drawings, 2- they impose to fit to very constrained standards, which implies, in particular, duplicating nodes making topological analysis considerably more difficult. RESULTS: We propose a method, called MetaViz, which enables to draw a genome-scale metabolic network and that also takes into account its structuration into pathways. This method consists in two steps: a clustering step which addresses the pathway overlapping problem and a drawing step which consists in drawing the clustered graph and each cluster. CONCLUSION: The method we propose is original and addresses new drawing issues arising from the no-duplication constraint. We do not propose a single drawing but rather several alternative ways of presenting metabolism depending on the pathway on which one wishes to focus. We believe that this provides a valuable tool to explore the pathway structure of metabolism.