project-idea

Spliceosome Disruption Atlas: Natural Compounds × Cancer

Crocin (from saffron) consistently downregulates spliceosomal machinery genes across all time points in liver cancer cells — a mechanism relevant to over 90% of cancers, yet largely untargeted by approved drugs.

Build a curated, searchable database of natural compounds with documented effects on spliceosome machinery genes, cross-referenced with cancer cell line transcriptomics data. The insight from this paper — that a widely consumed food compound hits a pan-cancer vulnerability — suggests there may be many such compounds hiding in existing datasets that haven't been connected to their spliceosome mechanism.

The project would mine public transcriptomics repositories (GEO, ArrayExpress) for studies where natural compounds were applied to cancer cell lines, then run a standardized pathway enrichment pipeline to score spliceosomal gene perturbation for each compound. Results would be presented as a ranked atlas: 'Top natural compounds by spliceosome disruption score, by cancer type.'

This would be valuable both as a research resource and as a starting point for medicinal chemistry — identifying natural scaffolds worth optimizing for selective spliceosome targeting. A companion analysis could flag which spliceosome genes are most frequently perturbed, narrowing the target space.

Who Is This For?

Cancer biologists, natural products chemists, and computational researchers interested in novel spliceosome-targeting strategies.

Skills & Tools Needed

R/Bioconductor or Python for transcriptomics analysis (DESeq2, edgeR, fgsea)
GEO/ArrayExpress API access for bulk data retrieval
Knowledge of spliceosome biology and gene sets (e.g., MSigDB spliceosome gene sets)
Database design (SQLite or Postgres) for the atlas backend
Web frontend for search and visualization (Streamlit, Shiny, or similar)

Feasibility

medium — Public data is abundant but cleaning and harmonizing transcriptomics studies across different platforms is time-consuming; a focused MVP on HCC studies could be built relatively quickly.

Inspired by: Time-Resolved Transcriptomics Reveal Spliceosomal Disruption and Senescence Pathways in Crocin-Treated Hepatocellular Carcinoma Cells

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