PLOS Computational Biology publishes research of significant importance that aims to deepen our understanding of life systems across various scales, from molecules and cells to patient populations and ecosystems, through the application of computational methods. The journal's readership includes life scientists and computational scientists who can leverage the important findings presented here to drive new discoveries. Research articles must clearly state their relevance to the appropriate sections, with specific requirements outlined in the submission guidelines. Articles should model various aspects of biological systems, demonstrate novelty in methods and science, and provide profound new biological insights. Typically, the reliability and significance of biological findings derived from computational approaches should be validated through experimental studies, although experimental validation is not required at the time of publication, relevant experiments should be cited whenever possible. Merely including computational validation of moderate biological findings does not qualify a manuscript for PLOS Computational Biology. Research articles designated as methods papers should describe outstanding methods that have been shown to be of special importance or have the potential to provide new biological insights. Enhancements to existing published methods will only be considered if they bring about significant new functionalities.