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Tip 4: Know your data and your question {#know-your-problem}

Having a well-defined scientific question and a clear analysis plan is crucial for carrying out a successful deep learning project. Just like it would be inadvisable to set foot in a laboratory and begin experiments without having a defined endpoint, a deep learning project should not be undertaken without defined goals. Foremost, it is important to assess if a dataset exists that can answer the biological question of interest using a deep learning-based approach. If so, obtaining this data (and associated metadata) and reviewing the study protocol should be pursued as early on in the project as possible. This can help to ensure that data is as expected and can prevent the wasted time and effort that occur when issues are discovered later on in the analytic process. For example, a publication or resource might purportedly offer an appropriate dataset that is found to be inadequate upon acquisition. The data may be unstructured when it is supposed to be structured, crucial metadata such as sample stratification might be missing, or the usable sample size may be different than expected. Any of these data issues might limit a researcher's ability to use deep learning to address the biological question at hand or might otherwise require adjustment before it can be used. Data collection should also be carefully documented, or a data collection protocol should be created and specified in the project documentation.

Information about the resources used, download dates, and dataset versions are critical to preserve. Doing so will help to minimize operational confusion and will increase the reproducibility of the analysis. Best practices for reproducibility also include sharing the collected dataset and metadata upon publication of the study, ideally in a public dataset repository if there are no ethical or privacy concerns and no copyright restrictions. While recommended and recognized dataset repositories may differ across disciplines, a list of general dataset repositories includes the Dryad repository [@doi:10.1038/npre.2010.4595.1] (https://datadryad.org/), Figshare [@doi:10.4103/0976-500X.81919] (https://figshare.com), Zenodo [@doi:10.3897/biss.3.37080] (https://zenodo.org), and the Open Science Framework [@doi:10.5195/jmla.2017.88] (https://osf.io). In addition, Gundersen et al. [@doi:10.1609/aimag.v39i3.2816] provide useful checklists summarizing best data sharing practices for reproducible research and open science.

Once the dataset is obtained, it is important to learn why and how the data was collected before beginning the analysis. The standardized metadata that exists in many fields can help with this (for example, see [@doi:10.1038/ng1201-365]). If at all possible, consulting with a subject matter expert who has experience with the type of data being used will minimize guesswork and likely increase the success rate of a deep learning project. For example, one might presume that data collected to test the impact of an intervention are derived from a randomized controlled trial. However, this is not always the case, as ethical or practical concerns often necessitate an observational study design that features prospectively or retrospectively collected data. In order to ensure similar distributions of important characteristics across study groups in the absence of randomization, such a study may have selected individuals in a fashion that best matches attributes such as age, gender, or weight. Passively collected datasets can have their own peculiarities, and other study designs can include samples that originate from the same study site, the oversampling of ethnic groups or zip codes, or sample processing differences. Such information is critical to accurate data analysis, and so it is imperative that practitioners learn about study design assumptions and data specificities prior to performing modeling. Other study design considerations that should not be overlooked include knowing whether a study involves biological or technical replicates or both. For example, the existence in a dataset of samples collected from the same individuals at different time points can have significant effects on analyses that make assumptions about sample size and independence (that is, non-independence can lower the effective sample size). Another potential issue is the existence of systematic biases, which can be induced by confounding variables and can lead to artifacts or so-called "batch effects." Consequently, models may learn to rely on the correlations that these systematic biases underpin, even though they are irrelevant to the scientific context of the study. This can lead to misguided predictions and misleading conclusions [@doi:10.1038/nrg2825]. Unsupervised learning and other exploratory analyses can help identify such biases in these datasets before applying a deep learning model.

Overall, practitioners should thoroughly study their data and understand its context and peculiarities before moving on to performing deep learning.