Statistical Inference and Community Detection in Proximity and Spatial Proteomics: Resolving the Organization of the Neuronal Proteome
Technological advances in protein mass spectrometry (MS), aka proteomics, haveenabled high-throughput quantification of spatially-resolved, subcellular-specific proteomes. Biological insight in these experiments depends upon sound statistical analysis. Despite the myriad of existing proprietary and open-source software solutions for statistical analysis of proteomics data, these tools suffer a drawback inherent in any general solution: a loss of specificity. These tools often fail to be easily adapted to analyze experiment-specific designs. I present a flexible, linear mixed-effects model framework for assessing differential abundance in protein mass spectrometry experiments. Combined with methods to identify communities of proteins in biological networks, I extend this framework to perform inference at the level of protein groups or modules. Using these software tools, I demonstrate how module-level insight in proximity and spatial proteomics generates hypotheses that identify foci of biological function and dysfunction which may underlie the neuropathology of disease.
Molecular biology
Animal diseases
Community Detection
Hypothesis Testing
Neurobiology of disease
Proximity Proteomics
Spatial Proteomics

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