Systems Analysis of Human Multigene Disorders

Christopher E. Mason, Sandra G. Porter, Todd M. Smith, Mason CE, Porter SG, Smith TM

In today's biology, studies have shifted to analyzing systems over discrete biochemical reactions and pathways. These studies depend on combining the results from scores of experimental methods that analyze DNA; mRNA; noncoding RNAs, DNA, RNA, and protein interactions; and the nucleotide modifications that form the epigenome into global datasets that represent a diverse array of "omics" data (transcriptional, epigenetic, proteomic, metabolomic). The methods used to collect these data consist of high-throughput data generation platforms that include high-content screening, imaging, flow cytometry, mass spectrometry, and nucleic acid sequencing. Of these, the next-generation DNA sequencing platforms predominate because they provide an inexpensive and scalable way to quickly interrogate the molecular changes at the genetic, epigenetic, and transcriptional level. Furthermore, existing and developing single-molecule sequencing platforms will likely make direct RNA and protein measurements possible, thus increasing the specificity of current assays and making it possible to better characterize "epi-alterations" that occur in the epigenome and epitranscriptome. These diverse data types present us with the largest challenge: how do we develop software systems and algorithms that can integrate these datasets and begin to support a more democratic model where individuals can capture and track their own medical information through biometric devices and personal genome sequencing? Such systems will need to provide the necessary user interactions to work with the trillions of data points needed to make scientific discoveries. Here, we describe novel approaches in the genesis and processing of such data, models to integrate these data, and the increasing ubiquity of self-reporting and self-measured genomics and health data.