Zazz: Variant Annotation and Exploration of Next Generation Sequencing Variants

Over the last 10 years, Next-Generation Sequencing (NGS) has become a powerful tool in clinical genetics and precision medicine. Techniques like Whole Genome Sequencing (WGS), Whole Exome Sequencing (WES) and Target Sequencing are commonly used for the elucidation of common and rare variants in mendelian and complex diseases. One of the most vital parts of NGS pipelines is the prioritization of annotated variants according to their clinical significance. During this process, a clinical geneticist is presented with annotation information from external databases for each of the thousands of potential variants. The vast amounts of data and the vague nature of existing guidelines for variant reporting, like ACMG (American College of Medical Genetics) can make this procedure very cumbersome and time consuming. Here we present the main computational challenges and existing solutions for this task. We also present Zazz, an online environment for variant annotation, query and exploration. Zazz can efficiently support the submission of complex and dynamically generated queries to hundreds of millions of variants each having hundreds of annotation fields. Zazz also leverages the capabilities of modern browsers to dynamically filter, explore and visualize multidimensional data.