Proteins are the complex molecules that dynamically regulate how our cells behave. Most diseases interfere with protein regulation, disrupting normal cellular function. Proteomics examines how protein expression levels shift in response to these disruptions. These datasets are vast and require specific computational tools for thorough analysis. Existing methods often focus on analyzing a single snapshot of the proteome at an arbitrary point in time rather than a collection of snapshots over time. As such, we developed the Framework for the Rhythmic Analysis of Preliminary Proteomics Experiments (FRAPPE), a Python package for time-series proteomics data analysis. This package of computational tools is geared towards biologists to generate hypotheses on the cellular mechanisms in charge of protein expression. Researchers can utilize FRAPPE's methods to quantify changes in the proteome based on the presence of experimental stimuli. Methods include phase delay, which identifies optimal alignments in protein expression patterns; rhythmic stability, which investigates changes in protein oscillation period length; and protein-protein interaction networks, which highlight functionality for proteins of interest. These methods leverage time-series expression data to dynamically evaluate how experimental conditions impact the proteome over time. FRAPPE was applied to data acquired from mice models from four experimental groups stratified by sex: control, mice with induced Alzheimer's disease conditions (AD), circadian disruption (SW), and a combination of both. Using this framework on these datasets presented sex-dependent proteomic shifts as a result of introducing AD/SW to mice models. Female mice presented more extreme period length alterations as well as having a higher overall presence of phase delays as a result of introducing circadian disruptions and Alzheimer's.
Acknowledgements: Data used in this project came from a collaboration with Rensselaer Polytechnic Institute thanks to a gift from the Warren Alpert Foundation