Analysis Proposal
Analysis Question
Can we validate co-regulation of BMAL1 and CLOCK in neurodegeneration-relevant contexts and confirm their functional relationship beyond mere textual co-occurrence?
Datasets
GTExBrain - human brain RNA-seq expression matrix for BMAL1/CLOCK co-expressionSTRINGdb v11.5 - protein-protein interaction network for BMAL1-CLOCK interaction evidenceDisGeNET - curated neurodegeneration gene-disease associations for BMAL1/CLOCK phenotype linksEurope PMC full-text corpus - literature mining for experimental evidence of BMAL1-CLOCK functional interaction
Methods
Spearman correlation of BMAL1 and CLOCK expression across brain regions and neurodegenerative disease cohorts (ADNI, Parkinson's Progression Markers Initiative)Text mining with dependency parsing on Europe PMC to extract explicit interaction predicates (phosphorylates, heterodimerizes, co-regulates) separating experimental from computational evidenceFisher's exact test for enrichment of circadian rhythm pathway genes among top BMAL1/CLOCK co-expressed genes in disease vs. control tissueCross-validation of STRING physical interaction confidence score against experimental binding assays reported in literature
Expected Outputs
- Correlation coefficient >0.6 in relevant brain regions would support functional co-regulation hypothesis
- Extraction of ≥3 independent experimental statements (e.g., co-immunoprecipitation, yeast two-hybrid) in neurodegeneration context would elevate co_discussed to mechanistically-supported edge
- Pathway enrichment p-value <0.05 for circadian regulation genes among co-expressed partners would confirm biological relevance
- Confirmation that STRING confidence score >0.9 aligns with primary experimental evidence would refute computational artifact origin of low confidence