Abstract As the availability of genetic and genomic data and analysis tools from large-scale cancer initiatives continues to increase, the need has become more urgent for a software environment that supports the entire “idea to dissemination” cycle of an integrative cancer genomics analysis. Such a system would need to provide access to a large number of analysis tools without the need for programming, be sufficiently flexible to accommodate the practices of non-programming biologists as well as experienced bioinformaticians, and would provide a way for researchers to encapsulate their work into a single “executable document” including not only the analytical workflow but also the associated descriptive text, graphics, and supporting research. To address these needs, we have developed GenePattern Notebook, based on the GenePattern environment for integrative genomics and the Jupyter Notebook system. GenePattern Notebook unites the phases of in silico research - experiment design, analysis, and publication - into a single interface. GenePattern Notebook presents a familiar lab notebook format that allows researchers to build a record of their work by creating “cells” containing text, graphics, and executable analyses. Researchers add, delete, and modify cells as the research evolves, supporting the initial research phases of prototyping and collaborative analysis. When an analysis is ready for publication, the same document that was used in the design and analysis phases becomes a research narrative that interleaves text, graphics, data, and executable analyses. The online notebook format allows researchers to explain the analytical and scientific considerations of each step in any level of detail, promoting reproducibility and adoption. Notebooks can also be shared between researchers for collaborative development. GenePattern Notebook features are designed to help nonprogramming users create and adapt notebooks. We have developed additional cell types allowing users to choose analyses, specify inputs, navigate results, send result files to new analyses, and create richly formatted text, all without the need for programming. A free online GenePattern Notebook workspace is available at http://www.genepattern-notebook.org, where researchers can develop, share, and publish notebook documents. We have provided a collection of template notebooks that walk users through various genomic and machine learning analyses, and are collaborating with cancer research laboratories to create integrative cancer genomics notebooks. Citation Format: Michael M. Reich, Thorin T. Tabor, Ted Liefeld, Barbara Hill, Helga Thorvaldsdottir, Jill P. Mesirov. The GenePattern Notebook environment for reproducible cancer research [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2279.