Validation of Predictions From a Novel Small-Sample Statistic of Valley Fever and Dysregulated Pathways and Increasing Statistical Power of Metabolite Identifiers Through Biocuration
Presented by Suraj Puvvadi, BASIS Scottsdale
Precision medicine is an approach to patient care that optimizes the efficiency and personalizes treatments based on transcriptomic, genomic, and metabolomic profiling. Rigorous curation of high throughput data is the first step towards efficient precision medicine. The purpose of this research is to validate findings from a novel small-sample valley fever statistic and to increase the statistical power of a precision medicine framework.
Disseminated coccidioidomycosis (DCM) is a chronic and fungal form of valley fever that’s prevalent in the southwestern parts of the United States. Currently, no anti-fungal treatment exists for DCM which makes it a lethal disease. Through literature biocuration and non-deterministic ratings of associations between DCM and ontological medical conditions, significant dysregulated molecular pathways were unveiled. Patient associations were ranked based on types of limitations, experimental nuances, and environmental setup. Interrater agreement scores and hypothesis testing were used to authenticate association ratings. A 71.4% rate of the novelty of dysregulated pathways was calculated which indicated the specific pathway relationships that need to be studied to create individualized treatments for DCM.
Metabolomic profiling is part of the foundation of precision medicine. An existing N-of-1 pathways framework uses transcriptomic data to create patient profiles targeting molecular pathways that need to be treated. Creating a metabolomic layer to the N-of-1 framework increases the accuracy and clarity of a treatment profile. After the systematic biocuration of unique serum metabolites, these novel metabolite identifiers are linked to molecular pathways from high-throughput databases which increases the statistical power of dysregulated pathways used in the N-of-1 framework. Following the metabolite curation, a significant statistical boost was observed. These new metabolites will be further investigated through literature biocuration, as in the DCM component.
Overall, this project emphasizes the importance of biocuration techniques and is the first step in producing individualized treatments to heal humanity.