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a python Environment for Tree Exploration Reviewed by Jaime Huerta-Cepas,corresponding author1 Joaquín Dopazo,2 and Toni Gabaldóncorresponding author1 Abstract Many bioinformatics analyses, ranging from gene clustering to phylogenetics, produce hierarchical trees as their main result. These are used to represent the relationships among different biological entities, thus facilitating their analysis and interpretation. A number of standalone programs are available that focus on tree visualization or that perform specific analyses on them. However, such applications are rarely suitable for large-scale surveys, in which a higher level of automation is required. Currently, many genome-wide analyses rely on tree-like data representation and hence there is a growing need for scalable tools to handle tree structures at large scale. Keywords: Python, spiking neurons, simulation, integrate and fire, teaching, neural networks, computational neuroscience, software Background Here we present the Environment for Tree Exploration (ETE), a python programming toolkit that assists in the automated manipulation, analysis and visualization of hierarchical trees. ETE libraries provide a broad set of tree handling options as well as specific methods to analyze phylogenetic and clustering trees. Among other features, ETE allows for the independent analysis of tree partitions, has support for the extended newick format, provides an integrated node annotation system and permits to link trees to external data such as multiple sequence alignments or numerical arrays. In addition, ETE implements a number of built-in analytical tools, including phylogeny-based orthology prediction and cluster validation techniques. Finally, ETEs programmable tree drawing engine can be used to automate the graphical rendering of trees with customized node-specific visualizations. Conclusions ETE provides a complete set of methods to manipulate tree data structures that extends current functionality in other bi