List2Net: Linking multiple lists of biological data in a network context

A common task in scientific research is the comparison of lists or sets of diverse biological entities such as biomolecules, ontologies, sequences and expression profiles. Such comparisons rely, one way or another, on calculating a measure of similarity either by means of vector correlation metrics, set operations such as union and intersection, or specific measures to capture, for example, sequence homology. Subsequently, depending on the data type, the results are often visualized using heatmaps, Venn, Euler, or Alluvial diagrams. While most of the abovementioned representations offer simplicity and interpretability, their effectiveness holds only for a limited number of lists and specific data types. Conversely, network representations provide a more versatile approach where data lists are viewed as interconnected nodes, with edges representing pairwise commonality, correlation, or any other similarity metric. Networks can represent an arbitrary number of lists of any data type, offering a holistic perspective and most importantly, enabling analytics for characterizing and discovering novel insights in terms of centralities, clusters and motifs that can exist in such networks. While several tools that implement the translation of lists to the various commonly used diagrams, such as Venn and Euler, have been developed, a similar tool that can parse, analyze the commonalities and generate networks from an arbitrary number of lists of the same or heterogenous content does not exist.

To address this gap, we introduce List2Net, a web-based tool that can rapidly process and represent lists in a network context, either in a single-layer or multi-layer mode, facilitating network analysis on multi-source/multi-layer data. Specifically, List2Net can seamlessly handle lists encompassing a wide variety of biological data types, such as named entities or ontologies (e.g., lists containing gene symbols), sequences (e.g., protein/peptide sequences), and numeric data types (e.g., omics-based expression or abundance profiles). Once the data is imported, the tool then (i) calculates the commonalities or correlations (edges) between the lists (nodes) of interest, (ii) generates and renders the network for visualization and analysis and (iii) provides a range of exporting options, including vector, raster format visualization but also the calculated edge lists and metrics in tabular format for further analysis in other tools. List2Net is a fast, lightweight, yet informative application that provides network-based holistic insights into the conditions represented by the lists of interest (e.g., disease-to-disease, gene-to-phenotype, drug-to-disease, etc.). As a case study, we demonstrate the utility of this tool applied on publicly available datasets related to Multiple Sclerosis (MS). Using the tool, we showcase the translation of various ontologies characterizing this specific condition on disease-to-disease subnetworks of neurodegenerative, autoimmune and infectious diseases generated from various levels of information such as genetic variation, genes, proteins, metabolites and phenotypic terms.