As powerful computational tools and 'big data' transform the biological sciences, bioinformatics training is becoming necessary to prepare the next generation of life scientists. Furthermore, because the tools and resources employed in bioinformatics are constantly evolving, bioinformatics learning materials must be continuously improved. In addition, these learning materials need to move beyond today's typical step-by-step guides to promote deeper conceptual understanding by students. One of the goals of the Network for Integrating Bioinformatics into Life Sciences Education (NIBSLE) is to create, curate, disseminate, and assess appropriate open-access bioinformatics learning resources. Here we describe the evolution, integration, and assessment of a learning resource that explores essential concepts of biological sequence similarity. Pre/post student assessment data from diverse life science courses show significant learning gains. These results indicate that the learning resource is a beneficial educational product for the integration of bioinformatics across curricula.